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Sample records for refractory hematologic malignancy

  1. XYY male and hematologic malignancy.

    Science.gov (United States)

    Oguma, N; Shigeta, C; Kamada, N

    1996-09-01

    Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.

  2. Hematologic malignancies during preg

    Directory of Open Access Journals (Sweden)

    Hossam K. Mahmoud

    2016-07-01

    Full Text Available Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient’s preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus.

  3. Telomerase Activation in Hematological Malignancies

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    Joana Ropio

    2016-09-01

    Full Text Available Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies.

  4. B-Cell Hematologic Malignancy Vaccination Registry

    Science.gov (United States)

    2016-12-28

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  5. Targeting hedgehog in hematologic malignancy.

    Science.gov (United States)

    Irvine, David A; Copland, Mhairi

    2012-03-08

    The Hedgehog pathway is a critical mediator of embryonic patterning and organ development, including hematopoiesis. It influences stem cell fate, differentiation, proliferation, and apoptosis in responsive tissues. In adult organisms, hedgehog pathway activity is required for aspects of tissue maintenance and regeneration; however, there is increasing awareness that abnormal hedgehog signaling is associated with malignancy. Hedgehog signaling is critical for early hematopoietic development, but there is controversy over its role in normal hematopoiesis in adult organisms where it may be dispensable. Conversely, hedgehog signaling appears to be an important survival and proliferation signal for a spectrum of hematologic malignancies. Furthermore, hedgehog signaling may be critical for the maintenance and expansion of leukemic stem cells and therefore provides a possible mechanism to selectively target these primitive cell subpopulations, which are resistant to conventional chemotherapy. Indeed, phase 1 clinical trials of hedgehog pathway inhibitors are currently underway to test this hypothesis in myeloid leukemias. This review covers: (1) the hedgehog pathway and its role in normal and malignant hematopoiesis, (2) the recent development of clinical grade small molecule inhibitors of the pathway, and (3) the potential utility of hedgehog pathway inhibition as a therapeutic strategy in hemato-oncology.

  6. Oncolytic Virotherapy for Hematological Malignancies

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    Swarna Bais

    2012-01-01

    Full Text Available Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM, and the myelodysplastic syndromes (MDSs primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic.

  7. Oral microflora in children with hematologic malignancies

    OpenAIRE

    M. F. Vecherkovskaya; G. V. Tets; B. V. Afanasiev; V. V. Tets

    2015-01-01

    The goal was a comprehensive study of oral microflora in healthy children and those with hematologic malignancies, based on the analysis of mixed microbial biofilms composition, isolation and identification of new previously unknown microorganisms. The material was obtained in children with hematological diseases in remission, 2–10 years aged, and for the control group from St. Petersburg schoolchildren and in kindergartens. We used microbiological, biochemical and molecular genetic methods, ...

  8. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Hovgaard, D; Skinhøj, P; Bangsborg, Jette Marie

    1988-01-01

    171 episodes of bacteremia and candidemia in 142 patients were recorded during the period 1981-1985 in patients with hematological malignancies. Overall mortality, within 1 week of onset of bacteremia, was 20%. Increased mortality was found in patients with poor disease-prognosis (39%), with gran......171 episodes of bacteremia and candidemia in 142 patients were recorded during the period 1981-1985 in patients with hematological malignancies. Overall mortality, within 1 week of onset of bacteremia, was 20%. Increased mortality was found in patients with poor disease-prognosis (39...

  9. Oral microflora in children with hematologic malignancies

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    M. F. Vecherkovskaya

    2015-06-01

    Full Text Available The goal was a comprehensive study of oral microflora in healthy children and those with hematologic malignancies, based on the analysis of mixed microbial biofilms composition, isolation and identification of new previously unknown microorganisms. The material was obtained in children with hematological diseases in remission, 2–10 years aged, and for the control group from St. Petersburg schoolchildren and in kindergartens. We used microbiological, biochemical and molecular genetic methods, including electron microscopy, proteomic analysis, sequencing and complete genome annotation. Microorganisms of 23 genera isolated as pure cultures and identified by biochemical activity from mixed microbial biofilm derived from saliva of healthy and sick children. In microflora of children with hematologic malignancies a previously unknown type of streptococci with a large number of antibiotic resistance genes was revealed. Differences in oral microbiota composition of healthy children and children with hematological diseases in remission were revealed. The microbiota of children with hematologic malignancies contains more genes controlling antibiotic resistance. Also, it was observed previously unknown bacterium of the genus Streptococcus.

  10. DC-based immunotherapy for hematological malignancies.

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    Kitawaki, Toshio

    2014-02-01

    Great advances have been made in the treatment of hematological malignancies, but achieving a definitive cure remains an elusive goal for the majority of patients. Antigen-specific tumor immunotherapy has the potential to improve clinical outcome in patients with such diseases by eradicating chemotherapy-resistant tumor cell clones without damaging normal tissues. Dendritic cells (DCs) serve as an essential link between the innate and the adaptive immune systems, acting as key controllers of antigen-specific T cell responses. Molecular identification of tumor-specific antigens recognized by T lymphocytes and technical advances in ex vivo generation of human DCs has enabled us to develop DC-based tumor immunotherapies (also called "DC vaccines"). To date, a large number of clinical trials of DC vaccines have been conducted for a variety of tumors, including hematological malignancies. Overall, these trials have demonstrated that DC vaccines have excellent safety profiles, moderate immunological activity, and mild clinical efficacy. To establish a role for DC vaccines in the treatment of hematological malignancies, we need both to define patient populations that can obtain clinical benefit from DC vaccines and to develop combination therapies that augment clinical efficacy of DC vaccines. In this review, I will describe current status of DC-based immunotherapy for hematological malignancies, and discuss future perspectives in this field.

  11. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Hovgaard, D; Skinhøj, P; Bangsborg, Jette Marie;

    1988-01-01

    171 episodes of bacteremia and candidemia in 142 patients were recorded during the period 1981-1985 in patients with hematological malignancies. Overall mortality, within 1 week of onset of bacteremia, was 20%. Increased mortality was found in patients with poor disease-prognosis (39%), with gran...

  12. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Bruun, B; Bangsborg, Jette Marie; Hovgaard, D

    1988-01-01

    The microorganisms isolated in 1981-1985 from 171 cases of septicemia in patients with hematological malignancies were on the whole the same as those found in 1970-1972. The distribution between species was also quite similar for the two periods except within staphylococci, where the isolation ra...

  13. Survival From Childhood Hematological Malignancies in Denmark

    DEFF Research Database (Denmark)

    Erdmann, Friederike; Winther, Jeanette Falck; Dalton, Susanne Oksbjerg

    2016-01-01

    BACKGROUND: Due to diverse findings as to the role of family factors for childhood cancer survival even within Europe, we explored a nationwide, register-based cohort of Danish children with hematological malignancies. METHODS: All children born between 1973 and 2006 and diagnosed with a hematolo...

  14. Role of RUNX1 in hematological malignancies.

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    Sood, Raman; Kamikubo, Yasuhiko; Liu, Paul

    2017-04-13

    RUNX1 is a member of the core-binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. RUNX1 is one of the most frequently mutated genes in a variety of hematological malignancies. Germ line mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies. Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome and leukemias of myeloid and lymphoid lineages, that is, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelomonocytic leukemia. More recent studies suggest that the wild-type RUNX1 is required for growth and survival of certain types of leukemia cells. The purpose of this review is to discuss the current status of our understanding about the role of RUNX1 in hematological malignancies.

  15. Improved radioimmunotherapy of hematologic malignancies

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    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  16. Role of Extracellular Vesicles in Hematological Malignancies

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    Stefania Raimondo

    2015-01-01

    Full Text Available In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules, a key role has been attributed to extracellular vesicles (EV, released from different cell types. EV (microvesicles and exosomes may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.

  17. Fertility considerations in young women with hematological malignancies

    DEFF Research Database (Denmark)

    Jadoul, Pascale; Kim, S Samuel; Andersen, Claus Yding

    2012-01-01

    The need for practice guidelines for fertility preservation in young women with hematological malignancies has been increased. To develop recommendations, publications relevant to fertility preservation and hematological cancers were identified through a PubMed database search and reviewed system...

  18. Targeting cell cycle regulators in hematologic malignancies

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    Eiman eAleem

    2015-04-01

    Full Text Available Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia, and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219, pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638 as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed.

  19. Vorinostat in solid and hematologic malignancies

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    Richon Victoria M

    2009-07-01

    Full Text Available Abstract Vorinostat (Zolinza®, a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs associated with monotherapy (n = 341 were fatigue (61.9%, nausea (55.7%, diarrhea (49.3%, anorexia (48.1%, and vomiting (32.8%, and Grade 3/4 drug-related AEs included fatigue (12.0%, thrombocytopenia (10.6%, dehydration (7.3%, and decreased platelet count (5.3%. The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days were nausea (48.4%, diarrhea (40.8%, fatigue (34.4%, vomiting (31.2%, and anorexia (20.4%, with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.

  20. Targeting cell cycle regulators in hematologic malignancies.

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    Aleem, Eiman; Arceci, Robert J

    2015-01-01

    Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC) that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs) not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia (AML), and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219), pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638) as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed.

  1. Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies

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    Reagan, John L.; Fast, Loren D.; Winer, Eric S.; Safran, Howard; Butera, James N.; Quesenberry, Peter J.

    2012-01-01

    Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells. PMID:22312367

  2. Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies

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    John L. Reagan

    2012-01-01

    Full Text Available Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells.

  3. Novel purine nucleoside analogues for hematological malignancies.

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    Korycka, Anna; Lech-Marańda, Ewa; Robak, Tadeusz

    2008-06-01

    Recently, the search for more effective and safer antineoplastic agents has led to synthesis and introduction into preclinical and clinical studies of a few new purine nucleoside analogues (PNA). Three of them: clofarabine (CAFdA), nelarabine, and forodesine (immucillin H, BCX-1777), despite belonging to the same group of drugs such as PNA, have shown some differences concerning their active forms, metabolic properties and mechanism of action. However, all these drugs have demonstrated promising activity in patients with relapsed and refractory acute lymphoblastic leukemia (ALL). CAFdA was approved for the therapy of relapsed or refractory ALL in the third line of treatment. It has proved promising in pediatric patients as well as in some patients who are able to proceed to allogenic hematopietic stem cell transplantation (HSCT). Moreover, the drug exhibits an efficacy in acute myeloid leukemia (AML), blast crisis of chronic myelogenous leukemia (CML-BP) and myelodysplastic syndrome (MDS). Nelarabine is recommended for T-ALL and T-cell lymphoblastic lymphoma (T-LBL) with the overall response rates ranging from 11 to 60%. However, the use of the drug is limited by potentially severe neurotoxicity. Forodesine is a purine nucleoside phosphorylase (PNP) inhibitor and it has shown activity in relapsed and refractory T- and B-cells leukemias as well as in cutaneous T-cell lymphoma (CTCL). Recently patented, a few of inventions in the field of pharmaceutical preparation of new PNA have also been published. Great hopes are currently set on the use of these drugs in the treatment of lymphoid and myeloid malignancies in adult and in pediatric patients, however ongoing studies will help to define their role in the standard therapy.

  4. Risk of hematological malignancies among Chernobyl liquidators

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    Kesminiene, Ausrele; Evrard, Anne-Sophie; Ivanov, Viktor K.; Malakhova, Irina V.; Kurtinaitis, Juozas; Stengrevics, Aivars; Tekkel, Mare; Anspaugh, Lynn R.; Bouville, André; Chekin, Sergei; Chumak, Vadim V.; Drozdovitch, Vladimir; Gapanovich, Vladimir; Golovanov, Ivan; Hubert, Phillip; Illichev, Sergei V.; Khait, Svetlana E.; Krjuchkov, Viktor P.; Maceika, Evaldas; Maksyoutov, Marat; Mirkhaidarov, Anatoly K.; Polyakov, Semion; Shchukina, Natalia; Tenet, Vanessa; Tserakhovich, Tatyana I.; Tsykalo, Aleksandr; Tukov, Aleksandr R.; Cardis, Elisabeth

    2010-01-01

    A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries in order to assess the effect of low-to-medium dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked in 1986–87 around the Chernobyl plant. 117 cases (69 leukemia, 34 non-Hodgkin Lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue) and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The Excess Relative Risk (ERR) per 100 mGy was 0.60 (90% confidence interval (CI): −0.02, 2.35). The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90%CI −0.38, 5.7). It is slightly higher than, but statistically compatible with, those estimated from a-bomb survivors and recent low dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over or underestimation of the risk in this study. PMID:19138033

  5. Role of leptin and leptin receptors in hematological malignancies.

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    Uddin, Shahab; Mohammad, Ramzi M

    2016-01-01

    Leptin is an adipose-derived cytokine that has an important role in bodyweight homeostasis and energy balance. There are a number of studies which have suggested that leptin and its receptors dysregulation play a critical role in the development of malignancies including hematological malignancies, mainly via activation of the JAK/STAT pathway which regulates downstream signaling pathways such as PI3K/AKT signaling and ERK1/2. In this review, current understandings of leptin/leptin receptors mediated pathogenesis in various lymphoid malignancies are described. Blocking of the leptin receptor might be a unique therapeutic approach for many hematological malignancies.

  6. Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise.

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    Bernard, M P; Bancos, S; Sime, P J; Phipps, R P

    2008-01-01

    There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastasis. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.

  7. Exploring Big Data in Hematological Malignancies: Challenges and Opportunities.

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    Westin, Gustavo F; Dias, Ajoy L; Go, Ronald S

    2016-08-01

    Secondary analysis of large datasets has become a useful alternative to address research questions outside the reach of clinical trials. It is increasingly utilized in hematology and oncology. In this review, we provided an overview of some examples of commonly used large datasets in the USA and described common research themes that can be pursued using such a methodology. We selected a sample of 14 articles on adult hematologic malignancies published in 2015 and highlighted their contributions as well as limitations.

  8. Adoptive therapy with CAR redirected T cells for hematological malignancies.

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    Li, Shiqi; Yang, Zhi; Shen, Junjie; Shan, Juanjuan; Qian, Cheng

    2016-04-01

    The survival of patients with hematological malignancies has been significantly improved due to the development of new therapeutic agents. However, relapse remains a major matter for concern. Recently, T cells engineered with chimeric antigen receptor (CAR) were reported to show unprecedented responses in a range of hematological malignancies. The persistence of the CAR-T cell can last for years and tends toward long-term antitumor memory by which relapses can be effectively prevented. The primary side effects that appear in most clinical trials are cytokine release syndrome and neurotoxicity. However, these symptoms can be treated and reversed. In this review, we describe CAR structure and function and summarize recent advances in CAR-T cell therapy in hematological malignancies.

  9. In the sandbox: palliative care and hematologic malignancies.

    Science.gov (United States)

    LeBlanc, Thomas W

    2014-02-01

    Palliative care specialists have had little involvement in the care of patients with hematologic malignancies. The reasons for this are not clear, because these patients certainly face a significant symptom burden, and many hematologic malignancies are either incurable or carry poor prognoses. For example, acute myeloid leukemia (AML) in patients over age 60 has a 5-year survival of less than 10%, akin to pancreatic cancer. Although most oncologists would agree with involving palliative care specialists in the case of advanced pancreatic cancer, few seem to consider this in the context of AML. Why should AML be any different?

  10. BACTERIAL INFECTIONS FOLLOWING SPLENECTOMY FOR MALIGNANT AND NONMALIGNANT HEMATOLOGIC DISEASES

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    Giuseppe Leone

    2015-10-01

    Full Text Available Splenectomy, while often necessary in otherwise healthy patients after major trauma, find its primary indication for patients with an underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP, Autoimmune Hemolytic Anemia (AIHA, Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infection found in splenectomized patients

  11. Prospective study of strongyloidosis in patients with hematologic malignancies

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    Graeff-Teixeira Carlos

    1997-01-01

    Full Text Available Immunocompromised individuals infected with Strongyloides stercoralis may develop severe hyperinfection or disseminated disease with high mortality. Patients with hematological malignancies are at risk because of immunodepression produced either by the disease or its treatment. A prospective study was undertaken at the Hospital de Clínicas de Porto Alegre, from July 1994 to July 1995. Seventy-two (HIV negative, had 3 stool samples collected at different days and had not received recent anti-helmintic therapy. Larvae, isolated in a modified Baermann method, were found in 6 patients, with a resultant prevalence of 8.3%. No complicated strongyloidosis was documented. The positive result for S. stercoralis larvae was significantly associated (p < 0.001 with eosinophilia. Knowledge of prevalence figures and incidence of severe disease is important to adequate guidelines for empirical treatment besides the rigorous search for strongyloidosis in patients with hematological malignancies.

  12. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    The adaptive immune system has the capacity to recognize and kill leukemic cells. However, immune tolerance mechanisms that normally protect healthy tissues from autoimmune effects prevent the development of effective antitumor immunity. Tumors use several different immunosuppressive mechanisms...... to evade otherwise effective T-cell responses. A growing number of immune evasion mechanisms have been characterized mainly in solid tumors. In hematological malignancies, less is known about how different immune escape mechanisms influence tumor immune evasion and the extent of their impact on ongoing...... immune responses. The present review highlights the potential role of three well-defined immunosuppressive mechanisms in hematological malignancies: (i) inhibitory T-cell pathways (especially programmed death ligand 1/programmed death 1 (PD-L1/PD-1)), (ii) regulatory immune cells, and (iii) metabolic...

  13. Improved radioimmunotherapy of hematologic malignancies. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  14. Improved radioimmunotherapy of hematologic malignancies. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  15. Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

    Science.gov (United States)

    Okada, Atsushi; Hosaka, Masami; Watanuki, Munenori; Itoi, Eiji

    2009-01-01

    Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies. PMID:19961270

  16. Human herpesvirus 6 in hematological malignancies.

    Science.gov (United States)

    Ogata, Masao

    2009-11-01

    Pathogenetic roles of human herpesvirus (HHV)-6 in lymphoproliferative diseases have been of continued interest. Many molecular studies have tried to establish a pathogenic role for HHV-6 in lymphoid malignancies. However, whether HHV-6 plays a role in these pathologies remains unclear, as positive polymerase chain reaction results for HHV-6 in those studies may reflect latent infection or reactivation rather than presence of HHV-6 in neoplastic cells. A small number of studies have investigated HHV-6 antigen expression in pathologic specimens. As a result, the lack of HHV-6 antigen expression on neoplastic cells argues against any major pathogenic role of HHV-6. The role of HHV-6 in childhood acute lymphoblastic leukemia (ALL) has also been of interest but remains controversial, with 2 studies documenting higher levels of HHV-6 antibody in ALL patients, and another 2 large-scale studies finding no significant differences in HHV-6 seroprevalences between ALL patients and controls. Alternatively, HHV-6 is increasingly recognized as an important opportunistic pathogen. HHV-6 reactivation is common among recipients of allogeneic stem cell transplantation (SCT), and is linked to various clinical manifestations. In particular, HHV-6 encephalitis appears to be significant, life-threatening complication. Most HHV-6 encephalitis develops in patients receiving transplant from an unrelated donor, particularly cord blood, typically around the time of engraftment. Symptoms are characterized by short-term memory loss and seizures. Magnetic resonance imaging typically shows limbic encephalitis. Prognosis for HHV-6 encephalitis is poor, but appropriate prophylactic measures have not been established. Establishment of preventive strategies against HHV-6 encephalitis represents an important challenge for physicians involved with SCT.

  17. Epigenetic mechanisms in the initiation of hematological malignancies

    Directory of Open Access Journals (Sweden)

    Ali Maleki

    2011-10-01

    Full Text Available Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs. Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS, CDKN2B (alias, P15, a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+ cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors are approved for the treatment of MDS.Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments

  18. Percutaneous Nephrolithotomy for Kidney Stones in Patients with Hematological Malignancy

    Directory of Open Access Journals (Sweden)

    Baris Kuzgunbay

    2016-07-01

    Full Text Available Aim: To define the alterations in the outcomes of percutaneous nephrolithotomy (PNL operations for kidney stones in patients with history of hematological malignancy (HM. Material and Method: Between 2000 and 2013, 1700 adult patients underwent PNL for the treatment of kidney stones in our institution. Four of these patients had a history of HM and considered to be HM group (n=4. Ten elderly (>65 years patients who had no history of operation, HM or any other co-morbide diseases were chosen as the control group (n=10. Surgical parameters, success rates, additional treatments and complications were evaluated. Results: Statistical analyses showed no significant differences between HM and control group according to stone area, operation time, fluoroscopy time, hospitalization time, %u2206Hb, blood transfusion rates and INR values (p>0.05. Statistical analyses revealed no significant differences between HM and control groups according to the success rates (p=0.470. Statistical analyses revealed no significant difference between groups for additional treatment requirements (p=0.882. No major perioperative complication was seen in both of the groups. Discussion: The treatment of kidney stone disease by PNL in patients with hematological malignancy is feasible, safe and effective. However, close cooperation with the Hematology Department before the operation is mandatory.

  19. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications.

    Science.gov (United States)

    Podar, Klaus; Anderson, Kenneth C

    2005-02-15

    Besides its role as an essential regulator of physiologic and pathologic angiogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopoiesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome.

  20. Information transfer by exosomes: A new frontier in hematologic malignancies.

    Science.gov (United States)

    Boyiadzis, Michael; Whiteside, Theresa L

    2015-09-01

    Exosomes are small (30-150 mm) vesicles secreted by all cell types and present in all body fluids. They are emerging as vehicles for delivery of membrane-tethered signaling molecules and membrane enclosed genes to target cells. Exosome-mediated information transfer allows for crosstalk of cells within the hematopoietic system and for interactions between hematopoietic cells and local or distant tissue cells. Exosomes carry physiological signals essential for health and participate in pathological processes, including malignant transformation. In hematologic malignancies, exosomes reprogram the bone marrow microenvironment, creating a niche for abnormal cells and favoring their expansion. The molecular and genetic mechanisms exosomes utilize to shuttle information between cells are currently being examined as are the potential roles exosomes play as biomarkers of disease or future therapeutic targets.

  1. Nanotechnology applications in hematological malignancies (Review).

    Science.gov (United States)

    Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

    2015-09-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up.

  2. Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies

    Science.gov (United States)

    Jabbour, Elias; Ottmann, Oliver G.; Deininger, Michael; Hochhaus, Andreas

    2014-01-01

    The phosphoinositide 3-kinase pathway represents an important anticancer target because it has been implicated in cancer cell growth, survival, and motility. Recent studies show that PI3K may also play a role in the development of resistance to currently available therapies. In a broad range of cancers, various components of the phosphoinositide 3-kinase signaling axis are genetically modified, and the pathway can be activated through many different mechanisms. The frequency of genetic alterations in the phosphoinositide 3-kinase pathway, coupled with the impact in oncogenesis and disease progression, make this signaling axis an attractive target in anticancer therapy. A better understanding of the critical function of the phosphoinositide 3-kinase pathway in leukemias and lymphomas has led to the clinical evaluation of novel rationally designed inhibitors in this setting. Three main categories of phosphoinositide 3-kinase inhibitors have been developed so far: agents that target phosphoinositide 3-kinase and mammalian target of rapamycin (dual inhibitors), pan-phosphoinositide 3-kinase inhibitors that target all class I isoforms, and isoform-specific inhibitors that selectively target the α, -β, -γ, or -δ isoforms. Emerging data highlight the promise of phosphoinositide 3-kinase inhibitors in combination with other therapies for the treatment of patients with hematologic malignancies. Further evaluation of phosphoinositide 3-kinase inhibitors in first-line or subsequent regimens may improve clinical outcomes. This article reviews the role of phosphoinositide 3-kinase signaling in hematologic malignancies and the potential clinical utility of inhibitors that target this pathway. PMID:24425689

  3. Notch signaling: its roles and therapeutic potential in hematological malignancies.

    Science.gov (United States)

    Gu, Yisu; Masiero, Massimo; Banham, Alison H

    2016-05-17

    Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway.

  4. Battling the hematological malignancies: the 200 years' war.

    Science.gov (United States)

    Lichtman, Marshall A

    2008-02-01

    The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients

  5. Hematopoietic reconstitution on the prognosis of hematological malignancies after allogenceic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张燕

    2012-01-01

    Objective To analyze the impact of the time to hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation(allo-HSCT) . Methods 173 patients with hematological malignancies treated with allo-HSCT (excluding umbilical cord blood transplantation)

  6. Molecular functions of metallothionein and its role in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Takahashi Shinichiro

    2012-07-01

    Full Text Available Abstract Metallothionein (MT was reported to be a potential negative regulator of apoptosis, and various reports have suggested that it may play roles in carcinogenesis and drug resistance, in at least a portion of cancer cells. The author summarizes the current understanding of the molecular functions of MT for tumor cell growth and drug resistance. These activities are regulated through intracellular metal ion modulation and free radical scavenging. Compared with analyses of solid tumors, few studies have analyzed the roles of MT in hematological malignancies. This review mainly describes the functions of MT in hematopoietic cells. Furthermore, through expression analyses of leukemias and lymphomas, the roles of MT in the biology of these diseases are particularly focused upon.

  7. Obinutuzumab in hematologic malignancies: lessons learned to date.

    Science.gov (United States)

    Illidge, Tim; Klein, Christian; Sehn, Laurie H; Davies, Andrew; Salles, Gilles; Cartron, Guillaume

    2015-11-01

    The routine use of anti-CD20 monoclonal antibodies (mAbs) has improved patient outcomes in CD20-positive non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Despite the clinical success achieved with rituximab, relapses are still common with further improvements in anti-CD20 mAb efficacy required. Many novel anti-CD20 antibodies are in development, but obinutuzumab is currently the only type II glycoengineered anti-CD20 mAb in clinical testing. Obinutuzumab has increased antibody-dependent cell-mediated cytotoxicity, reduced complement-dependent cytotoxicity and enhanced direct non-apoptotic cell death. In preclinical models, obinutuzumab induced superior tumor remission compared with rituximab at the equivalent dose levels, and was active in rituximab-refractory tumors. Obinutuzumab exhibits encouraging efficacy as monotherapy in NHL, and combined with chemotherapy in relapsed/refractory NHL and treatment-naïve symptomatic CLL. In a recent randomized, phase III trial in patients with untreated comorbid CLL, overall response rate was significantly greater (78% vs. 65%, Pobinutuzumab plus chlorambucil vs. rituximab plus chlorambucil. Obinutuzumab is a type II anti-CD20 antibody that utilizes distinct mechanisms of action relative to type I antibodies like rituximab and has led to significant clinical improvement over rituximab in a phase III trial in CLL. Further trials are ongoing to determine whether such improvements in outcome will be seen in CD20-positive B-cell malignancies.

  8. Curcumin-induced Histone Acetylation in Malignant Hematologic Cells

    Institute of Scientific and Technical Information of China (English)

    Junbin HU; Yan WANG; Yan CHEN

    2009-01-01

    This study investigated the inhibitory effects of curcumin on proliferation of hemato-logical malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacety-lation levels.The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay.The expression of acetylated histone-3 (H3) in Raji,HL60 and K562 cells,and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS.The results showed curcumin inhibited pro-liferation of Raji cells significantly in a time- and dose-dependent fashion,while exhibited low toxic-ity in PBMCs.Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested.In conclusion,curcumin inhibited proliferation of Raji cells selec-tively,enhanced the level of acetylated H3 in Raji,HL60,and K562 cells,which acted as a histone deacetylase inhibitor like TSA.Furthermore,up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.

  9. Association of the blood eosinophil count with hematological malignancies and mortality

    DEFF Research Database (Denmark)

    Andersen, Christen L; Siersma, Volkert D; Hasselbalch, Hans C;

    2015-01-01

    Blood eosinophilia (≥0.5x10(9) /l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut-offs for referral to specialist hematology care....... From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000-2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable...... logistic regression to calculate odds ratios (ORs) for the 4-year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16x10(9) /l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above...

  10. XK469R in Treating Patients With Refractory Hematologic Cancer

    Science.gov (United States)

    2013-02-07

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

    Directory of Open Access Journals (Sweden)

    W. Yao

    2015-01-01

    Full Text Available Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT. We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB], and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC dose was 4.07 (range 2.76-6.02×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days and had platelet counts of >20×109/L on median day +35 (range 17-70 days. Sixteen patients (61.5% experienced pre-engraftment syndrome (PES, and six (23.1% patients progressed to acute graft-versus-host disease (GVHD. The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74, 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS, disease-free survival (DFS, and non-relapse mortality (NRM rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

  12. Acquired uniparental disomy of chromosome 9p in hematologic malignancies.

    Science.gov (United States)

    Wang, Linghua; Wheeler, David A; Prchal, Josef T

    2016-08-01

    Acquired uniparental disomy (aUPD) is a common and recurrent molecular event in human cancers that leads to homozygosity for tumor suppressor genes as well as oncogenes, while retaining the diploid chromosomal complement. Because of the lack of copy number change, aUPD is undetectable by comparative genome hybridization, so the magnitude of this genetic change was underappreciated in the past. 9p aUPD was first described in 2002 in patients with polycythemia vera (PV). Since then, systematic application of genomewide single-nucleotide polymorphism arrays has indicated that 9p aUPD is the most common chromosomal aberration in myeloproliferative neoplasms (MPNs), contributing to discovery of the PV-defining mutation JAK2V617F21. It was also found in other myeloid and lymphoid malignancies, though at a relatively lower frequency. By leading to JAK2V617F 23 homozygosity, 9p aUPD plays a causal role in the development of PV and is also associated with less favorable clinical outcomes. It is also possible that new targets other than JAK2V617F 25 are present within 9p aUPD that may contribute to diversity of PV outcome and phenotype. This review summarizes recent discoveries on 9p aUPD in hematologic malignancies and discusses possible underlying mechanisms and potential roles of 9p aUPD in the pathogenesis of PV, the relationship between 9p aUPD and JAK2V617F29, and possible new cancer-related targets within the 9p aUPD region.

  13. Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies

    Science.gov (United States)

    2009-02-12

    Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Secondary AML; Myelodysplastic Syndrome (MDS); Secondary MDS; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia (JMML); Paroxysmal Nocturnal Hemoglobinuria (PNH); Lymphoma, Non-Hodgkin; Hodgkin Disease

  14. ESCHERICHIA COLI: AN IMPORTANT PATHOGEN IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Daniel Olson

    2014-08-01

    Full Text Available Abstract Background Escherichia coli (E. coli is a pathogen of great concern in immunosuppressed patients.  While antimicrobial prophylactic therapy has become the standard, the emergence of resistant pathogens has some questioning its use.  This study describes our experience with E.coli as a pathogen in neutropenic patients with a hematologic malignancy, and addresses future directions of treatment for this patient population. Methods A retrospective chart review of 245 E.coli bacteremia patients at Moffitt Cancer Center from 05/18/02 – 05/15/12 was conducted. Patients were identified via microbiology laboratory computerized records. Results The included patients experienced clinically significant E.coli bacteremia resulting in a median hospital stay of 14.7 days.  Several patients developed severe sepsis requiring the use of pressor and ventilator therapy. Conclusions E.coli is a major pathogen in these patient populations resulting in extended hospital stays and specialized treatment to overcome their E.coli bacteremia. The data supports the use of fluoroquinolone prophylactic therapy, however, earlier detection and treatment of neutropenic infection is needed.

  15. Thrombotic and infectious complications of central venous catheters in patients with hematological malignancies.

    NARCIS (Netherlands)

    Boersma, R.S.; Jie, K.S.; Verbon, A.; Pampus, EC van; Schouten, H.C.

    2008-01-01

    Central venous catheters (CVCs) have considerably improved the management of patients with hematological malignancies, by facilitating chemotherapy, supportive therapy and blood sampling. Complications of insertion of CVCs include mechanical (arterial puncture, pneumothorax), thrombotic and infectio

  16. Favorable outcome of chronic disseminated candidiasis in four pediatric patients with hematological malignancies.

    NARCIS (Netherlands)

    Donker, A.E.; Mavinkurve-Groothuis, A.M.C.; Die, L.E. van; Verweij, P.E.; Hoogerbrugge, P.M.; Warris, A.

    2012-01-01

    Four children were diagnosed with chronic disseminated candidiasis (CDC) during treatment for hematological malignancies. All presented with persistent fever, not responsive to broad-spectrum antibiotics, abdominal distension and hepatosplenomegaly. Two children needed artificial ventilation because

  17. Nutritional Assessment of Children With Hematological Malignancies and Their Subsequent Tolerance to Chemotherapy

    OpenAIRE

    2012-01-01

    Background: Our research goals were to assess the prevalence of malnutrition in children with cancer, observe malnutrition's effect on tolerance to chemotherapy, and establish malnutrition at onset as one of the prognostic factors in children with hematological malignancies.

  18. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death

    DEFF Research Database (Denmark)

    Andersen, Christen Lykkegaard; Siersma, Volkert Dirk; Hasselbalch, Hans Carl;

    2013-01-01

    Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one...... differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (...

  19. Association of the blood eosinophil count with hematological malignancies and mortality.

    Science.gov (United States)

    Andersen, Christen L; Siersma, Volkert D; Hasselbalch, Hans C; Vestergaard, Hanne; Mesa, Ruben; Felding, Peter; Olivarius, Niels D F; Bjerrum, Ole W

    2015-03-01

    Blood eosinophilia (≥0.5 × 10(9) /l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut-offs for referral to specialist hematology care. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000-2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable logistic regression to calculate odds ratios (ORs) for the 4-year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16 × 10(9) /l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above the median eosinophil count. At the 99th percentile, corresponding to an eosinophil count of 0.75 × 10(9) /l, risks of hematological malignancies were increased more than twofold with OR (95% C.I.) of 2.39 (1.91-2.99). Interestingly, risks reached a plateau around an eosinophil count of 1.0 × 10(9) /l. Risks also increased when the eosinophil count approached zero. Here, counts associated relatively more with acute myeloid leukemia and myelodysplastic syndromes whereas counts above 0.16 × 10(9) /l associated more with myeloproliferative neoplasms. Eosinophil counts associate with hematological malignancies and mortality even below the definition of eosinophilia. The observed plateau of risks around 1.0 × 10(9) /l is important for physicians encountering patients with eosinophilia since even mild-to-moderate eosinophilia according to traditional definitions confers maximally increased risks of subsequent/subclinical hematological malignancy.

  20. Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update.

    Science.gov (United States)

    Villafuerte-Gutierrez, Paola; Villalon, Lucia; Losa, Juan E; Henriquez-Camacho, Cesar

    2014-01-01

    Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.

  1. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    Science.gov (United States)

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  2. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  3. Three cases of hematologic malignancies in pregnancy: Still difficult to diagnose and hard to treat

    Directory of Open Access Journals (Sweden)

    Özlem Bozoklu Akkar

    2016-06-01

    Full Text Available The hematologic malignancies during pregnancy are rare and there is often a delay in diagnosis because of the similarity of symptoms to those of pregnancy. Therefore the management of disease necessitates many medical, psychological, social, and ethical problems for the patient and physician to deal with and a multidisciplinary approach of a medical team consisting of hematologist, obstetrician and pediatrician. Here, we present three cases of hematologic malignancies during pregnancy; acute myeloid leukemia, acute lymphoblastic leukemia, and B-cell non-Hodgkin’s lymphoma that were admitted to our clinic with different clinical presentation. There is a need for measures to increase the awareness of health workers related to hematologic malignancies during antenatal care.

  4. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Janmaat, Maarten L.; Mutis, Tuna

    2016-01-01

    CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hema...

  5. Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Castillo JJ

    2014-02-01

    Full Text Available Jorge J Castillo,1 Meera Iyengar,2 Benjamin Kuritzky,2 Kenneth D Bishop2 1Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, 2Division of Hematology and Oncology, Rhode Island Hospital, Providence, RI, USA Abstract: In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical and clinical studies using PI3K inhibitors, focusing on the advances made in hematologic malignancies. Keywords: phosphatidylinositol-3-kinase pathway, inhibitors, leukemia, lymphoma, myeloma

  6. CT and MR imaging of central nervous system effects of therapy in patients treated for hematological malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, A. [Dept. of Radiology, Saint-Louis Hospital AP-HP, Paris (France); Dept. of Radiology, Univ. of California, San Francisco, CA (United States); Miaux, Y. [Dept. of Radiological Reading Services, SYNARC, San Francisco, CA (United States); Lafitte, F. [Dept. of Radiology, Adolphe de Rothschild Foundation, Paris (France); Zahar, J.R. [Lab. of Microbiology, Necker School of Medicine, Paris (France); Gluckman, E. [Dept. of Bone Marrow Transplantation, Saint-Louis Hospital AP-HP, Paris (France)

    2003-12-01

    The purpose of this article is to present the imaging appearance of central nervous system effects of therapy that may occur in patients treated for hematological malignancies. Imaging in these patients relates to complications of high-dose therapy, bone marrow transplantation, infections occurring in immunocompromised patients, central nervous system dysfunction due to failure of other organ systems, or cerebral hemorrhages due to platelet refractoriness. Rapid and accurate diagnosis is essential but often difficult, as neurological manifestations are rarely disease specific. Neurological imaging, in combination with electrophysiological studies as well as blood and cerebrospinal fluid investigations, may be helpful for diagnosing most of these complications, as well as in differentiating between the manifestations of the underlying disease and complications of the treatment. (orig.)

  7. XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy.

    Science.gov (United States)

    Camus, Vincent; Miloudi, Hadjer; Taly, Antoine; Sola, Brigitte; Jardin, Fabrice

    2017-02-14

    Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies. Recent reports have shown molecular alterations in the gene encoding XPO1 and showed a mutation hotspot (E571K) in the following two hematological malignancies with similar phenotypes and natural histories: primary mediastinal diffuse large B cell lymphoma and classical Hodgkin's lymphoma. Emerging evidence suggests that the mutant XPO1 E571K plays a role in carcinogenesis, and this variant is quantifiable in tumor and plasma cell-free DNA of patients using highly sensitive molecular biology techniques, such as digital PCR and next-generation sequencing. Therefore, it was proposed that the XPO1 E571K variant may serve as a minimal residual disease tool in this setting. To clarify and summarize the recent findings on the role of XPO1 in B cell hematological malignancies, we conducted a literature search to present the major publications establishing the landscape of XPO1 molecular alterations, their impact on the XPO1 protein, their interest as biomarkers, and investigations into the development of new XPO1-targeted therapies in B cell hematological malignancies.

  8. Prevalence of Human T-lymphotropic virus type 1 (HTLV-1) Infection in Patients with Hematologic Disorders and Non-Hematologic Malignancies in a Tertiary Referral Hospital.

    Science.gov (United States)

    Jalaeikhoo, Hasan; Soleymani, Mosayeb; Rajaeinejad, Mohsen; Keyhani, Manoutchehr

    2017-04-01

    Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified in human. The current evidence is quite scarce regarding the potential role of HTLV-1 in pathogenesis of hematologic disorders and non-hematologic malignancies. The aim of this study is to evaluate the prevalence of HTLV-1 infection in patients with hematologic disorders and non-hematologic malignancies. This cross-sectional study was conducted on 505 cases of definite diagnosis of hematologic disorders including malignancies as well as non-malignant disorders such as polycythemia and myelofibrosis and non-hematologic malignancies referred to the hematology and medical oncology ward at Army Hospital 501 from January 2015 to January 2016. A 3-mL blood specimen was collected from each patient and tested for the presence of anti-HTLV-1 antibodies using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS software package version 19 (IBM, New York, USA). Data are presented as mean ± SD if normally distributed and otherwise as median (range). Totally, 242 (48%) males and 263 (52%) females with a mean ± SD age of 52.09 ± 16.24 were enrolled in this study. In total, there were 9 (1.78%) cases positive for HTLV-1 infection including 4 males and 5 females. Seven out of 287 (2.4%) patients with hematologic disorders were infected by HTLV-1. In non-hematologic malignancies, 2 out of 211 cases were positive (0.9%). There was no HTLV-1 positive case in 7 patients with both hematologic and non-hematologic disorders. The difference in HTLV-1 infection prevalence between patients with hematologic disorders and non-hematologic malignancies was not statistically significant different (P = 0.31). There was no association between sex and transfusion history with HTLV-1 infection in this population (P = 0.9 and 0.7, respectively). Our study revealed that the prevalence of HTLV-1 in hematologic disorders is higher than the general population. Further larger prospective studies are

  9. Genome-Wide Arrays in Routine Diagnostics of Hematological Malignancies

    NARCIS (Netherlands)

    Simons, Annet; Sikkema-Raddatz, Birgit; de Leeuw, Nicole; Konrad, Nicole Claudia; Hastings, Rosalind J.; Schoumans, Jacqueline

    2012-01-01

    Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization ana

  10. Genome-wide arrays in routine diagnostics of hematological malignancies

    NARCIS (Netherlands)

    Simons, A.; Sikkema-Raddatz, B.; Leeuw, N. de; Konrad, N.C.; Hastings, R.J.; Schoumans, J.

    2012-01-01

    Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization ana

  11. Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

    Directory of Open Access Journals (Sweden)

    Paola Villafuerte-Gutierrez

    2014-01-01

    Full Text Available Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.

  12. Role of Microvessel Density and Vascular Endothelial Growth Factor in Angiogenesis of Hematological Malignancies

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    Rashika Chand

    2016-01-01

    Full Text Available Angiogenesis plays an important role in progression of tumor with vascular endothelial growth factor (VEGF being key proangiogenic factor. It was intended to study angiogenesis in different hematological malignancies by quantifying expression of VEGF and MVD in bone marrow biopsy along with serum VEGF levels and observing its change following therapy. The study included 50 cases of hematological malignancies which were followed for one month after initial therapy along with 30 controls. All of them were subjected to immunostaining by anti-VEGF and factor VIII antibodies on bone marrow biopsy along with the measurement of serum VEGF levels. Significantly higher pretreatment VEGF scores, serum VEGF levels, and MVD were observed in cases as compared to controls (p<0.05. The highest VEGF score and serum VEGF were observed in chronic myeloid leukemia and maximum MVD in Non-Hodgkin’s Lymphoma. Significant decrease in serum VEGF levels after treatment was observed in all hematological malignancies except for AML. To conclude angiogenesis plays an important role in pathogenesis of all the hematological malignancies as reflected by increased VEGF expression and MVD in bone marrow biopsy along with increased serum VEGF level. The decrease in serum VEGF level after therapy further supports this view and also lays the importance of anti angiogenic therapy.

  13. 78 FR 5186 - Clinical Flow Cytometry in Hematologic Malignancies; Public Workshop; Request for Comments

    Science.gov (United States)

    2013-01-24

    ... location. Webcast participants will be sent technical system requirements after registration and will be... need for such products to assist clinical laboratories in performing this testing. FDA has been working... HUMAN SERVICES Food and Drug Administration Clinical Flow Cytometry in Hematologic Malignancies; Public...

  14. Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

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    Laure Farnault

    2012-01-01

    Full Text Available Hematological malignancies treatment improved over the last years resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed. Therefore, sustainment of long-term remission is crucial. Immune system has a key role in tumor surveillance. Natural killer (NK cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. Nevertheless, tumor cells develop various mechanisms to escape from NK cells innate immune pressure. Abnormal NK cytolytic functions have been described in nearly all hematological malignancies. We present here various mechanisms involved in the escape of hematological malignancies from NK cells surveillance: NK cells quantitative deficiency and NK cell qualitative deficiency by increased inhibition signaling or decreased activating stimuli. A challenge of immunotherapy is to restore an efficient antitumor response. A combination of classical therapy plus immune modulation strategies will soon become a standard of care for hematological malignancies.

  15. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

  16. Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies

    Science.gov (United States)

    Parahym, Ana Maria Rabelo de Carvalho; Rolim, Pedro José; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Leite, Edinalva Pereira; de Morais, Vera Lúcia Lins; Macêdo, Danielle Patrícia Cerqueira; de Lima, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-01-01

    We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID:26273269

  17. Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma.

    Science.gov (United States)

    Ferrario, Andrea; Merli, Michele; Basilico, Claudia; Maffioli, Margherita; Passamonti, Francesco

    2017-03-01

    The role of interleukin-6 (IL-6) in tumorigenesis and in particular in haematological malignancies is crucial. On the basis of the favourable results obtained in the subset of multicentric Castleman disease (MCD), Siltuximab, a chimeric, human-murine, immunoglobulin (Ig) Gk monoclonal antibody directed against human IL-6 has been evaluated in haematological malignancies such as multiple myeloma, myelodisplastic syndromes and non Hodgkin lymphomas. Areas covered: This review discusses available data related to the role of IL-6 as a therapeutic target, the characteristics of Siltuximab in term pharmacokinetics and pharmacodynamics properties and a detailed analysis of the studies involving haematological malignancies with a peculiar focus on non Hodgkin lymphoma. Expert opinion: The results obtained with Siltuximab in haematological malignancies and in particular with non Hodgkin lymphoma are inferior to those obtained in MCD. The complex interaction between malignant clones, inflammatory background and host response could justify this difference. New interesting areas of study are the role of Siltuximab in early phase of multiple myeloma (smoldering multiple myeloma) and if there may be a possible future application in the treatment of Waldenström macroglobulinemia.

  18. Extracorporeal Membrane Oxygenation Support in Adult Patients with Hematologic Malignancies and Severe Acute Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Tai Sun Park

    2016-08-01

    Full Text Available Background: Administering extracorporeal membrane oxygenation (ECMO to critically ill patients with acute respiratory distress syndrome has substantially increased over the last decade, however administering ECMO to patients with hematologic malignancies may carry a particularly high risk. Here, we report the clinical outcomes of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO. Methods: We performed a retrospective review of the medical records of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO at the medical intensive care unit of a tertiary referral hospital between March 2010 and April 2015. Results: A total of 15 patients (9 men; median age 45 years with hematologic malignancies and severe acute respiratory failure received ECMO therapy during the study period. The median values of the Acute Physiology and Chronic Health Evaluation II score, Murray Lung Injury Score, and Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score were 29, 3.3, and -2, respectively. Seven patients received venovenous ECMO, whereas 8 patients received venoarterial ECMO. The median ECMO duration was 2 days. Successful weaning of ECMO was achieved in 3 patients. Hemorrhage complications developed in 4 patients (1 pulmonary hemorrhage, 1 intracranial hemorrhage, and 2 cases of gastrointestinal bleeding. The longest period of patient survival was 59 days after ECMO initiation. No significant differences in survival were noted between venovenous and venoarterial ECMO groups (10.0 vs. 10.5 days; p = 0.56. Conclusions: Patients with hematologic malignancies and severe acute respiratory failure demonstrate poor outcomes after ECMO treatment. Careful and appropriate selection of candidates for ECMO in these patients is necessary.

  19. Management of patients with hematological malignancies undergoing coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Deepak Borde

    2013-01-01

    Full Text Available The number of patients with a previously diagnosed malignancy who need cardiac surgery is increasing. Patients with hematological malignancies represent only 0.38% of all patients undergoing cardiac surgery. The literature in this subset of patients is limited to only a few retrospective case series, with limited number of patients undergoing emergency cardiac surgery. We describe three cases with hematological malignancies namely chronic myelogenous leukemia, acute promyelocytic leukemia and chronic lymphocytic leukemia presenting for coronary artery bypass grafting (CABG. Two patients were taken up for emergency CABG in view of ongoing ischemia, one of them was on preoperative intra-aortic balloon pump support. No mortality was observed. Two patients needed transfusion of blood products which was guided by thromboelastography. One patient developed superficial sternal wound infection requiring antibiotic therapy.

  20. Nonrandom involvement of chromosomal segments in human hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1977-01-01

    The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphenomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration of the number and/or location of genes related to nucleic acid biosynthesis. It would be expected that the proliferative advantage provided by various chromosome aberrations differs in patients with different genetic constitutions.

  1. Haploidentical transplantation for hematologic malignancies: where do we stand?

    OpenAIRE

    Fuchs, Ephraim J.

    2012-01-01

    The fundamental obstacle to the successful application of partially HLA-mismatched related donor, or HLA-haploidentical stem cell transplantation, is the strength of the host and donor T-cell response to allogeneic HLA molecules, which results in increased incidences of graft failure, GVHD, and nonrelapse mortality. The holy grail of haplo-SCT is to mitigate host-versus-graft and graft-versus-host responses while preserving immune responses to infection and the patient’s malignancy. Two strat...

  2. A risk prediction score for invasive mold disease in patients with hematological malignancies.

    Directory of Open Access Journals (Sweden)

    Marta Stanzani

    Full Text Available BACKGROUND: A risk score for invasive mold disease (IMD in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. METHODS: We retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008 to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012. RESULTS: Of the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of 5% of IMD, with a negative predictive value (NPV of 0.99, (95% CI 0.98-0.99. During 2009-2012, patients with a calculated risk score at admission of 6 (0.9% vs. 10.6%, P <0.001. CONCLUSION: An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate "screening-out" of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis.

  3. Superficial Fungal Infections in Patients with Hematologic Malignancies: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Berna Ülgen Altay

    2011-06-01

    Full Text Available Background and Design: Dermatophytes, yeasts and some moulds settle on the skin and mucosal surfaces in immunocompetent individuals as commensals. Patients with diabetes mellitus, HIV-positive patients, organ transplant recipients and the patients with malignancies are predisposed to develop superficial fungal infections. We aimed to determine the prevalence, clinical and mycological features of superficial fungal infections in patients with hematologic malignancies in this case-control study.Material and Method: Eighty patients with hematologic malignancies (49 men, 31 women and 50 healthy individuals (22 men, 28 women randomly selected at our clinical department as controls were included to this study between 2003 and 2004. The mean age was 52±1.85 years in patients and 41.56±2.04 years in controls. All patients were inspected for superficial fungal infections. Skin scrapings and mucosal swabs were obtained from the toe web, inguinal region, any suspicious lesion and oral mucosa. Nail samples were also collected. All samples were examined by direct microscopy and cultured in Sabouraud dextrose agar (SDA. The yeasts were established in germ-tube production. Results: Fifty-six (70% of 80 patients with hematologic malignancies had fungal colonization, whereas 21 (42% of 50 controls had. For both groups, oral mucosa was the predominant area that fungus was mostly isolated from. A rising number of non-dermatophyte moulds (26% was observed. Candida albicans was the predominant agent isolated from the culture.Conclusion: The prevalence of superficial fungal infection was higher in patients with hematologic malignancies (being immunosuppressed than in the normal population. Candida albicans was the predominant isolated agent that was found in our study. We observed oral mucosa candidal infection mostly. The rising number of non-dermatophyte moulds is attributed to long-term use of antibiotics, cytotoxic chemotherapies and antifungals.

  4. Comparison of survival of adolescents and young adults with hematologic malignancies in Osaka, Japan.

    Science.gov (United States)

    Nakata-Yamada, Kayo; Inoue, Masami; Ioka, Akiko; Ito, Yuri; Tabuchi, Takahiro; Miyashiro, Isao; Masaie, Hiroaki; Ishikawa, Jun; Hino, Masayuki; Tsukuma, Hideaki

    2016-01-01

    The survival gap between adolescents and young adults (AYAs) with hematological malignancies persists in many countries. To determine to what extent it does in Japan, we investigated survival and treatment regimens in 211 Japanese AYAs (15-29 years) in the Osaka Cancer Registry diagnosed during 2001-2005 with hematological malignancies, and compared adolescents (15-19 years) with young adults (20-29 years). AYAs with acute lymphoblastic leukemia (ALL) had a poor 5-year survival (44%), particularly young adults (29% vs. 64% in adolescents, p = 0.01). Additional investigation for patients with ALL revealed that only 19% of young adults were treated with pediatric treatment regimens compared with 45% of adolescents (p = 0.05). Our data indicate that we need to focus on young adults with ALL and to consider establishing appropriate cancer care system and guidelines for them in Japan.

  5. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    Science.gov (United States)

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  6. Advanced Targeted, Cell and Gene-Therapy Approaches for Pediatric Hematological Malignancies: Results and Future Perspectives

    OpenAIRE

    Chiara Francesca Magnani; Sarah eTettamanti; Francesca eMaltese; Nice eTurazzi; Andrea eBiondi; Ettore eBiagi

    2013-01-01

    Despite the survival of pediatric patients affected by hematological malignancies being improved in the last 20 years by chemotherapy and hematopoietic stem cell transplantation (HSCT), a significant amount of patients still relapses. Treatment intensification is limited by toxic side effects and is constrained by the plateau of efficacy, while the pipeline of new chemotherapeutic drugs is running short. Therefore, novel therapeutic strategies are essential and researchers around the world ar...

  7. Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with hematological malignancies.

    Directory of Open Access Journals (Sweden)

    Erik Ahlstrand

    Full Text Available Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Örebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97% belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs; Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65% and ST215 (28/373, 8%. Ninety three percent (226/243 of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78% of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%, compared with 34/100 (34% in other STs (p<0.001. In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

  8. Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation from different donors in treatment of hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    余正平

    2013-01-01

    Objective To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT) from unrelated donors and that from related donors in treatment of hematologic malignancies. Methods

  9. Targeting the PI3K/mTOR Pathway in Pediatric Hematologic Malignancies

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    Sarah K Tasian

    2014-05-01

    Full Text Available A complex interplay of intracellular signaling networks orchestrates normal cell growth and survival, including translation, transcription, proliferation, and cell cycle progression. Dysregulation of such signals occurs commonly in many malignancies, thereby giving the cancer cell a survival advantage, but also providing possible targets for therapeutic intervention. Activation of the phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt/mammalian target of rapamycin (mTOR signaling pathway contributes to the proliferative advantage of malignant cells and may confer resistance to chemotherapy in various hematologic malignancies. The initial mTOR inhibitor, sirolimus (also known as rapamycin, was first discovered in 1975 in the soil of Easter Island. Sirolimus was originally developed as an anti-fungal agent given its macrolide properties, but was approved by the Food and Drug Administration (FDA in 1999 as an immunosuppressive agent for renal transplantation patients once its T cell suppression characteristics were recognized. Shortly thereafter, recognition of sirolimus’s ability to inhibit cellular proliferation and cell cycle progression brought sirolimus to the forefront as a possible inhibitor of mTOR. In the subsequent decade, the functional roles of the mTOR protein have been more fully elucidated, and this protein is now known to be a key regulator in a highly complex signaling pathway that controls cell growth, proliferation, metabolism, and apoptosis. This article discusses the dysregulation of PI3K/mTOR signaling in hematologic malignancies, including acute and chronic leukemias, lymphomas, and lymphoproliferative disorders. The current repertoire of PI3K/mTOR pathway inhibitors in development and clinical trials to date are described with emphasis upon pediatric hematologic malignancies (Figure 1. Investigation of small molecule inhibitors of this complex signaling network is an active area of oncology drug development.

  10. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies.

    Science.gov (United States)

    Gill, Saar; June, Carl H

    2015-01-01

    On July 1, 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania. This is the first personalized cellular therapy for cancer to be so designated and occurred 25 years after the first publication describing genetic redirection of T cells to a surface antigen of choice. The peer-reviewed literature currently contains the outcomes of more than 100 patients treated on clinical trials of anti-CD19 redirected T cells, and preliminary results on many more patients have been presented. At last count almost 30 clinical trials targeting CD19 were actively recruiting patients in North America, Europe, and Asia. Patients with high-risk B-cell malignancies therefore represent the first beneficiaries of an exciting and potent new treatment modality that harnesses the power of the immune system as never before. A handful of trials are targeting non-CD19 hematological and solid malignancies and represent the vanguard of enormous preclinical efforts to develop CAR T-cell therapy beyond B-cell malignancies. In this review, we explain the concept of chimeric antigen receptor gene-modified T cells, describe the extant results in hematologic malignancies, and share our outlook on where this modality is likely to head in the near future.

  11. Comparison of fluconazole and posaconazole for fungal prophylaxis in high- risk patients with hematological malignity

    Directory of Open Access Journals (Sweden)

    Selçuk Kaya

    2014-03-01

    Full Text Available Objective: To compare the frequency of fungal infection and mortality rates in patients with hematological malignity and receiving either flucanazole (FLU or posaconazole (POS prophylaxis. Methods: This retrospective, observational study investigated fungal prophylaxis in patients with a high risk of invasive fungal infections (IFIs and diagnosed with hematological malignity at our hospital hematology clinic between 01.01.2011 and 01.01.2013. FLU (n=70 was the prophylactic regimen between 2011 and 2012 which was replaced by POS (n=35 in the following period. The incidence and mortality rates of IFIs developing in the two periods were compared. Results: The incidence of IFI in patients administered FLU prophylaxis was 22/70 (31%, compared to 13/35 (37% in the patients receiving POS. Incidence of invasive pulmonary aspergillosis (IPA in the FLU group was 21/70 (31%, compared to 9/35 (26% in the POS group. The mortality rate in the group receiving FLU prophylaxis was 17 (24%, compared to 4 (11% in the POS group. The difference was attributed to causes other than fungal infection. Results of subgroup analysis performed for AML were similar to the general findings in terms of both incidences of fungal infection and of mortality levels. In multivariate analysis, mean duration of neutropenia was correlated with prophylaxis failure. Conclusion:We conclude that both agents can be successfully used in fungal infection prophylaxis for patients at high risk for IFI. J Microbiol Infect Dis 2014;4(1: 1-6

  12. Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses.

    Science.gov (United States)

    Saret, Cayla J; Winn, Aaron N; Shah, Gunjan; Parsons, Susan K; Lin, Pei-Jung; Cohen, Joshua T; Neumann, Peter J

    2015-03-19

    We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money. © 2015 by The American Society of Hematology.

  13. INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

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    Giuseppe La Torre

    2016-09-01

    Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.

  14. Allergic conditions and risk of hematological malignancies in adults: a cohort study

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    Schwartzbaum Judith

    2004-11-01

    Full Text Available Abstract Background Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. Methods The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886–1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969–99 and cancer incidence was ascertained from the Swedish Cancer Registry. Results Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0–4.5 and RR = 1.6, 95% CI 0.8–3.5, respectively. There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0–5.3. Conclusion In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies.

  15. Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies

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    Baixin Ye

    2017-01-01

    Full Text Available A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR T-cell therapy and engineered T-cell receptor (TCR T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells. In clinic trials, CAR-T-cell- and TCR-T-cell-based adoptive immunotherapy have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. The purpose of the present review is to (1 provide a detailed overview of the multiple mechanisms for immune evasion related with T-cell-based therapies; (2 provide a current summary of the applications of CAR-T-cell- as well as neoantigen-specific TCR-T-cell-based adoptive immunotherapy and routes taken to overcome immune evasion; and (3 evaluate alternative approaches targeting immune evasion via optimization of CAR-T and TCR-T-cell immunotherapies.

  16. Results of candidemia treatment in children with hematologic malignancies: single center experience

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    I. I. Kalinina

    2014-07-01

    Full Text Available Candidemia is one of the most serious infectious complications in children with hematological malignancies and has a high morta lity rate.Seven-year experience of candidemia diagnosis and therapy in patients with various hematologic malignancies w as analyzed. Candidemia registered in 37 patients (AML and MDS — 14, ALL — 10, solid tumors — 5, histocytic syndromes — 4, AA — 3, other non-malignancy diseases— 2. C. non-albicans (36 isolates from 32 patients was common cause of, while C. albicans isolated in 5 patients (8 strains. Antifungal prophylactic therapy was applied to 31 patients. 22 patients at the time of candidemia have neutropenia (< 0.5 × 10 9/l. Main clinical manifestations were febrile fever (100 % cases and pneumonia (21.6 % cases. Less frequent multiorgan failure (8.1 %, septic shoc k (5.4 %, chronic disseminated candidiasis (5.4 % and meningitis (2.7 % were registered. All patients received antifungal therapy (monotherapy — 17, combination therapy — 20. Central venous catheter removed in 21 patients. In 14 patients hematopoietic recovery w as registered, none of these patients died, while from group of patients without hematopoietic recovery 6 patients died (p = 0.0001. Recurrent candidemia episodes were seen in 4 patients. Overall survival was 0.37 ± 0.09.

  17. Results of candidemia treatment in children with hematologic malignancies: single center experience

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    I. I. Kalinina

    2011-01-01

    Full Text Available Candidemia is one of the most serious infectious complications in children with hematological malignancies and has a high morta lity rate.Seven-year experience of candidemia diagnosis and therapy in patients with various hematologic malignancies w as analyzed. Candidemia registered in 37 patients (AML and MDS — 14, ALL — 10, solid tumors — 5, histocytic syndromes — 4, AA — 3, other non-malignancy diseases— 2. C. non-albicans (36 isolates from 32 patients was common cause of, while C. albicans isolated in 5 patients (8 strains. Antifungal prophylactic therapy was applied to 31 patients. 22 patients at the time of candidemia have neutropenia (< 0.5 × 10 9/l. Main clinical manifestations were febrile fever (100 % cases and pneumonia (21.6 % cases. Less frequent multiorgan failure (8.1 %, septic shoc k (5.4 %, chronic disseminated candidiasis (5.4 % and meningitis (2.7 % were registered. All patients received antifungal therapy (monotherapy — 17, combination therapy — 20. Central venous catheter removed in 21 patients. In 14 patients hematopoietic recovery w as registered, none of these patients died, while from group of patients without hematopoietic recovery 6 patients died (p = 0.0001. Recurrent candidemia episodes were seen in 4 patients. Overall survival was 0.37 ± 0.09.

  18. Patients treated for hematologic malignancies: affected sexuality and health-related quality of life.

    Science.gov (United States)

    Olsson, Cecilia; Sandin-Bojö, Ann-Kristin; Bjuresäter, Kaisa; Larsson, Maria

    2015-01-01

    Sexuality in relation to health-related quality of life (HRQoL) is studied mostly with younger patients as participants who have undergone bone marrow transplantation and concerns fertility and/or sexual function. However, patients with hematologic malignancies such as diffuse large B-cell lymphoma, chronic lymphocytic leukemia, or acute myeloid leukemia most often are above their fifties and are treated with chemotherapy or chemoimmunotherapy. The aim was to examine how sexuality and HRQoL were affected in patients with hematologic malignancies at baseline compared with 1 month after chemotherapy or chemoimmunotherapy. Data were collected twice with a longitudinal design using the Sexual Adjustment Questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire. Thirty-two patients responded. The importance of sexuality, sexual desire, and sexual ability decreased 1 month after treatment and distressing symptoms such as feelings of tiredness occurred more frequently compared with baseline. At the same time, improvement in global health status/quality of life as well as affected functions in HRQoL was reported. The findings are of significance for nurses in cancer care as these highlight that sexuality and HRQoL need to be considered also in older patients with hematologic malignancies when fertility issues are of less importance. To meet these patients' needs regarding sexuality and HRQoL, the care must provide greater consistency and continuity. One way is to organize the care in a patient-centered way where patients continuously meet a nurse guided by the idea of holistic individual nursing care throughout the care trajectory.

  19. Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Debernardo, Robert [Department of Obstetrics and Gynecology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Radivoyevitch, Tomas [Department of Epidemiology and Biostatistics, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Fabien, Jeffrey; Dobbins, Donald C.; Zhang Yuxia; Brindle, James [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States)

    2012-09-01

    Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

  20. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death.

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    Andersen, Christen Lykkegaard; Siersma, Volkert Dirk; Hasselbalch, Hans Carl; Lindegaard, Hanne; Vestergaard, Hanne; Felding, Peter; de Fine Olivarius, Niels; Bjerrum, Ole Weis

    2013-10-01

    Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (eosinophilia. From the Danish Cancer Registry and the Danish Civil Registration System, we ascertained hematological malignancies and death within 3 years following the DIFF. Using multivariable logistic regression odds ratios (ORs) were calculated and adjusted for previous eosinophilia in a DIFF, sex, age, year, month, C-reactive protein, previous cancer, and comorbidity. ORs for developing Hodgkin's lymphoma (HL) was significantly increased in individuals exhibiting severe eosinophilia, OR = 9.09 (C.I. 2.77-29.84), P = 0.0003. The association with classical myeloproliferative neoplasms (cMPNs) showed an increasing risk with OR = 1.65 (1.04-2.61) P = 0.0322 and OR = 3.87 (1.67-8.96) P = 0.0016 for mild and severe eosinophilia. Eosinophilia was in a similar fashion associated with chronic lymphatic leukemia (CLL), OR = 2.57 (1.50-4.43), P = 0.0006 and OR = 5.00 (1.57-15.94), P = 0.0065, and all-cause death, OR of 1.16 (1.09-1.24), P eosinophilia and HL and cMPNs, and in addition for the first time demonstrate a dose-dependent association between eosinophilia and CLL as well as death. Unexplained eosinophilia should prompt clinicians to consider conditions where early diagnosis may improve prognosis. Copyright © 2013 Wiley Periodicals, Inc.

  1. Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy.

    Science.gov (United States)

    Dubbelman, Anne-Charlotte; Rosing, Hilde; Darwish, Mona; D'Andrea, Denise; Bond, Mary; Hellriegel, Edward; Robertson, Philmore; Beijnen, Jos H; Schellens, Jan H M

    2013-03-01

    Bendamustine is an alkylating agent with clinical activity against a variety of hematologic malignancies and solid tumors. To assess the roles of renal and hepatic drug elimination pathways in the excretion and metabolism of bendamustine, a mass balance study was performed in patients with relapsed or refractory malignancies. A single 60-minute intravenous dose of 120 mg/m(2), 80-95 μCi (14)C-bendamustine hydrochloride was administered to six patients, followed by collection of blood, urine, and fecal samples at specified time points up to day 8 or until the radioactivity of the 24-hour urine and fecal collections was below 1% of the administered dose (whichever was longer). Total radioactivity (TRA) was measured in all samples, and concentrations of unchanged bendamustine and its metabolites γ-hydroxy-bendamustine (M3), N-desmethyl-bendamustine (M4), and dihydroxy bendamustine (HP2) were determined in plasma and urine, using validated liquid chromatography-tandem mass spectrometry methods. The mean recovery of TRA in excreta was 76% of the radiochemical dose. Approximately half of the administered dose was recovered in urine and a quarter in feces. Less than 5% of the administered dose was recovered in urine as unchanged bendamustine. Bendamustine clearance from plasma was rapid, with a half-life of ~40 minutes. Plasma concentrations of M3, M4, and HP2 were very low relative to bendamustine concentrations. Plasma levels of TRA were higher and more sustained as compared with plasma concentrations of bendamustine, M3, M4, and HP2, suggesting the presence of one or more longer-lived (14)C-bendamustine-derived compounds. Fatigue (50%) and vomiting (50%) were the most frequent treatment-related adverse events. A grade 3/4 absolute lymphocyte count decrease occurred in all patients at some point during the study. Bendamustine is extensively metabolized, with subsequent excretion in both urine and feces. Accumulation of bendamustine is not anticipated in cancer

  2. Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001-2007): stable incidence but changing epidemiology of a still frequently lethal infection

    National Research Council Canada - National Science Library

    Sipsas, Nikolaos V; Lewis, Russell E; Tarrand, Jeffrey; Hachem, Ray; Rolston, Kenneth V; Raad, Issam I; Kontoyiannis, Dimitrios P

    2009-01-01

    The incidence, epidemiology, Candida species distribution, resistance patterns, and outcome of candidemia in high-risk hematologic malignancy and/or stem cell transplantation patients have not been...

  3. The Prevalence of fungal infections in children with hematologic malignancy in Ali-Asghar Children Hospital between 2005 and 2010

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    Ansari, Sh.; Shirzadi, E; Elahi, M

    2015-01-01

    Background A fungal infection represents a growing problem in children with hematologic malignancies, during chemotherapy induced neutropenia. Fungal colonization is considered a major risk factor for subsequent fungal infections. The aim of this retrospective study was to evaluate prevalence of fungal infection among children admitted to hospital between 2005 and 2010 in Tehran, Iran. Materials and Methods 617 hematological patients in the age range of neoteric to 19 years old were enrolled ...

  4. The Impact of Chemotherapy on Hepatitis B Antibody Titer in Patients with Hematological Malignancies

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    Münci Yağcı

    2015-09-01

    Full Text Available Objective: To investigate the influence of chemotherapy (CT on HBsAb titer in patients receiving CT due to hematological malignancy. Materials and Methods: The data of 75 patients who received CT with the diagnosis of various hematological malignancies and who had serum HBsAb levels measured prior to and after the cessation of CT were evaluated retrospectively. Results: The median age of the patients was 52 years (range: 16-78 with 49 (65% males and 26 (35% females. Median HBsAb titer decreased significantly after CT compared to the pre-CT median HBsAb titer [68 (range: 0-1000 vs. 100 (range: 6.2-1000] (p=0.001. In subgroup analysis, median HBsAb titer decreased significantly after CT in acute leukemia patients [110 (range: 6.2-1000 vs. 67.8 (range: 0-1000] (p=0.003 and in patients receiving intensive CT [97.2 (range: 6.2-1000 vs. 71 (range: 0-1000] (p=0.036. The decrease in median HBsAb titer was significant in male patients (p<0.001. HBsAb became negative after CT in 9 patients who were HBcAb-negative and had lower pre-CT HBsAb levels. Conclusion: HBsAb decreased after CT, especially in acute leukemia and male patients, and in patients receiving intensive CT.

  5. Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies.

    Science.gov (United States)

    Kreitman, Robert J

    2009-01-01

    Immunotoxins are molecules that contain a protein toxin and a ligand that is either an antibody or a growth factor. The ligand binds to a target cell antigen, and the target cell internalizes the immunotoxin, allowing the toxin to migrate to the cytoplasm where it can kill the cell. In the case of recombinant immunotoxins, the ligand and toxin are encoded in DNA that is then expressed in bacteria, and the purified immunotoxin contains the ligand and toxin fused together. Among the most active recombinant immunotoxins clinically tested are those that are targeted to hematologic malignancies. One agent, containing human interleukin-2 and truncated diphtheria toxin (denileukin diftitox), has been approved for use in cutaneous T-cell lymphoma, and has shown activity in other hematologic malignancies, including leukemias and lymphomas. Diphtheria toxin has also been targeted by other ligands, including granulocyte-macrophage colony-stimulating factor and interleukin-3, to target myelogenous leukemia cells. Single-chain antibodies containing variable heavy and light antibody domains have been fused to truncated Pseudomonas exotoxin to target lymphomas and lymphocytic leukemias. Recombinant immunotoxins anti-Tac(Fv)-PE38 (LMB-2), targeting CD25, and RFB4(dsFv)-PE38 (BL22, CAT-3888), targeting CD22, have each been tested in patients. Major responses have been observed after failure of standard chemotherapy. The most successful application of recombinant immunotoxins today is in hairy cell leukemia, where BL22 has induced complete remissions in most patients who were previously treated with optimal chemotherapy.

  6. Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

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    Knut Liseth

    2010-01-01

    Full Text Available In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

  7. The Basic Biology of PP2A in Hematologic Cells and Malignancies.

    Science.gov (United States)

    Haesen, Dorien; Sents, Ward; Lemaire, Katleen; Hoorne, Yana; Janssens, Veerle

    2014-01-01

    Reversible protein phosphorylation plays a crucial role in regulating cell signaling. In normal cells, phosphoregulation is tightly controlled by a network of protein kinases counterbalanced by several protein phosphatases. Deregulation of this delicate balance is widely recognized as a central mechanism by which cells escape external and internal self-limiting signals, eventually resulting in malignant transformation. A large fraction of hematologic malignancies is characterized by constitutive or unrestrained activation of oncogenic kinases. This is in part achieved by activating mutations, chromosomal rearrangements, or constitutive activation of upstream kinase regulators, in part by inactivation of their anti-oncogenic phosphatase counterparts. Protein phosphatase 2A (PP2A) represents a large family of cellular serine/threonine phosphatases with suspected tumor suppressive functions. In this review, we highlight our current knowledge about the complex structure and biology of these phosphatases in hematologic cells, thereby providing the rationale behind their diverse signaling functions. Eventually, this basic knowledge is a key to truly understand the tumor suppressive role of PP2A in leukemogenesis and to allow further rational development of therapeutic strategies targeting PP2A.

  8. SDF1-3′A polymorphism is associated with increased risk of hematological malignancy: a meta-analysis

    Science.gov (United States)

    Zhang, Xiaowen; Fan, Yang; Li, Zhijie

    2017-01-01

    CXCL12 (also named SDF1), a member of the chemokine family, has been demonstrated to play an important role in the progression of multiple types of hematological malignancy. Several recent studies have shown that SDF1-3′A polymorphism (rs1801157) is associated with susceptibility to hematological malignancy, but published studies’ results are disputed. Therefore, we performed a meta-analysis to evaluate the relationship between SDF1-3′A polymorphism and the risk of hematological malignancy based on the existing literature. We carried out a comprehensive literature search using the Web of Science, PubMed, Cochrane Library, Chinese Wan Fang, and Chinese National Knowledge Infrastructure databases. And the raw data were extracted and calculated in standard steps of meta-analysis. Overall, nine qualified studies containing 1,576 cases and 1,674 controls were included in the ultimate meta-analysis. The pooled results displayed that AA genotype significantly increased the risk of hematological malignancy. The result of subgroup analysis further indicated that SDF1-3′A polymorphism was significantly associated with increased risk of chronic myeloid leukemia, Hodgkin’s lymphoma and multiple myeloma, but was not associated with increased risk of acute myeloid leukemia and non-Hodgkin’s lymphoma. In addition, SDF1-3′A polymorphism was associated with increased risk of hematological malignancy in Africans and Asians, but not in Caucasians. In conclusion, our meta-analysis firstly demonstrated that SDF1-3′A polymorphism may be associated with increased risk of hematological malignancy, especially for chronic myeloid leukemia, Hodgkin’s lymphoma, multiple myeloma and the non-Caucasian population. Nevertheless, these conclusions should be reconfirmed by more evidence from large sample sized studies. PMID:28352190

  9. Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors.

    Science.gov (United States)

    Inoue, Daichi; Nagai, Yuya; Mori, Minako; Nagano, Seiji; Takiuchi, Yoko; Arima, Hiroshi; Kimura, Takaharu; Shimoji, Sonoko; Togami, Katsuhiro; Tabata, Sumie; Yanagita, Soshi; Matsushita, Akiko; Nagai, Kenichi; Imai, Yukihiro; Takegawa, Hiroshi; Takahashi, Takayuki

    2010-05-01

    Bacillus cereus is a growing concern as a cause of life-threatening infections in patients with hematologic malignancies. However, the risk factors for patients with unfavorable outcomes have not been fully elucidated. At our institution, we observed the growth of B. cereus in blood culture in 68 patients with (23) or without (45) hematologic malignancies treated from September 2002 to November 2009. We defined a case as having sepsis when more than two blood culture sets were positive for B. cereus or only a single set was positive in the absence of other microorganisms in patients who had definite infectious lesions. We determined 12 of 23 patients with hematologic malignancies as having sepsis, as well as 10 of 45 patients without hematologic malignancies (p = 0.012). Of the 12 patients with hematologic malignancies, four patients with acute leukemia died of B. cereus sepsis within a few days. In our cohort, risk factor analysis demonstrated that a neutrophil count of 0/mm(3), central venous (CV) catheter insertion, and the presence of central nervous system (CNS) symptoms were significantly associated with a fatal prognosis (p = 0.010, 0.010, and 0.010, respectively). Analysis of data from our cohort in conjunction with those from 46 previously reported patients with B. cereus sepsis identified similar risk factors, that is, acute leukemia, extremely low neutrophil count, and CNS symptoms (p = 0.044, 0.004, and 0.002, respectively). These results indicate that appropriate prophylaxis and early therapeutic intervention against possible B. cereus sepsis are crucially important in the treatment of hematologic malignancies.

  10. Liquid biopsies for liquid tumors:emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    Jay Hocking; Sridurga Mithraprabhu; Anna Kalff; Andrew Spencer

    2016-01-01

    Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.

  11. Expression of p16INK4A and p14ARF in hematological malignancies.

    Science.gov (United States)

    Taniguchi, T; Chikatsu, N; Takahashi, S; Fujita, A; Uchimaru, K; Asano, S; Fujita, T; Motokura, T

    1999-11-01

    The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.

  12. [Managing of platelet transfusion refractoriness of haematological malignancies. Experience IPC-EFSAM].

    Science.gov (United States)

    Dettori, I; Ladaique, P

    2014-11-01

    The platelet refractoriness is a complication of transfusion treatments potentially dramatic in onco-haematology. Chemo-treatment of haematological malignancies or packs of allogeneic bone marrow transplants require iterative platelet transfusion requirements. The discovery of a platelet refractoriness along with its support should be the most reactive as possible but also adapted to the cause. In the case of allo-immunization, it may be expected. The purpose of this presentation is to recall the different etiologies and perform a feedback on the support transfusion platelet of onco-haematology adult patients at Institut Paoli-Calmettes (IPC) in partnership with the EFSAM.

  13. Diverse hematological malignancies including hodgkin-like lymphomas develop in chimeric MHC class II transgenic mice.

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    Silke H Raffegerst

    Full Text Available A chimeric HLA-DR4-H2-E (DR4 homozygous transgenic mouse line spontaneously develops diverse hematological malignancies with high frequency (70%. The majority of malignancies were distributed equally between T and B cell neoplasms and included lymphoblastic T cell lymphoma (LTCL, lymphoblastic B cell lymphoma (LBCL, diffuse large B cell lymphoma (DLBCL, the histiocyte/T cell rich variant of DLBCL (DLBCL-HA/T cell rich DLBCL, splenic marginal zone lymphoma (SMZL, follicular B cell lymphoma (FBL and plasmacytoma (PCT. Most of these neoplasms were highly similar to human diseases. Also, some non-lymphoid malignancies such as acute myeloid leukemia (AML and histiocytic sarcoma were found. Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also detected that had CD30(+ Hodgkin/Reed-Sternberg (H/RS-like cells, representing a tumor type not previously described in mice. Analysis of microdissected H/RS-like cells revealed their origin as germinal center B cells bearing somatic hypermutations and, in some instances, crippled mutations, as described for human Hodgkin lymphoma (HL. Transgene integration in an oncogene was excluded as an exclusive driving force of tumorigenesis and age-related lymphoma development suggests a multi-step process. Thus, this DR4 line is a useful model to investigate common molecular mechanisms that may contribute to important neoplastic diseases in man.

  14. Neuroleptic Malignant Syndrome Associated with Refractory Acute Disseminated Encephalomyelitis

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    Silvia R. Delgado

    2016-04-01

    Full Text Available We present the case of a young man who was transferred to our hospital with worsening acute disseminated encephalomyelitis (ADEM despite treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. He developed neuroleptic malignant syndrome (NMS without the use of dopamine-modulating drugs. His progressive clinical improvement started after treatment with intravenous cyclophosphamide and methylprednisolone. In our patient, acute demyelination with severe bilateral inflammation of the basal ganglia could have caused a state of central dopamine depletion, creating proper conditions for the development of NMS. Significant clinical improvement of our case after treatment with intravenous cyclophosphamide and steroids provides further evidence for a possible role of the inflammatory lesions in the pathogenesis of NMS in association with ADEM.

  15. Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure.

    Science.gov (United States)

    Adda, Mélanie; Coquet, Isaline; Darmon, Michaël; Thiery, Guillaume; Schlemmer, Benoît; Azoulay, Elie

    2008-10-01

    The current trend to manage critically ill hematologic patients admitted with acute respiratory failure is to perform noninvasive ventilation to avoid endotracheal intubation. However, failure of noninvasive ventilation may lead to an increased mortality. Retrospective study to determine the frequency of noninvasive ventilation failure and identify its determinants. Medical intensive care unit in a University hospital. All consecutive patients with hematologic malignancies admitted to the intensive care unit over a 10-yr period who received noninvasive ventilation. A total of 99 patients were studied. Simplified Acute Physiology Score II at admission was 49 (median, interquartile range, 39-57). Fifty-three patients (54%) failed noninvasive ventilation and required endotracheal intubation. Their PaO2/FiO2 ratio was significantly lower (175 [101-236] vs. 248 [134-337]) and their respiratory rate under noninvasive ventilation was significantly higher (32 breaths/min [30-36] vs. 28 [27-30]). Forty-seven patients (89%) who failed noninvasive ventilation required vasopressors. Hospital mortality was 79% in those who failed noninvasive ventilation, and 41% in those who succeeded. Patients who failed noninvasive ventilation had a significantly longer intensive care unit stay (13 days [8-23] vs. 5 [2-8]) and a significantly higher rate of intensive care unit-acquired infections (32% compared with 7%). Factors independently associated with noninvasive ventilation failure by multivariate analysis were respiratory rate under noninvasive ventilation, longer delay between admission and noninvasive ventilation first use, need for vasopressors or renal replacement therapy, and acute respiratory distress syndrome. Failure of noninvasive ventilation occurs in half the critically ill hematologic patients and is associated with an increased mortality. Predictors of noninvasive ventilation failure might be used to guide decisions regarding intubation.

  16. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Michael; J; Ricci; Jeffrey; A; Medin; Ronan; S; Foley

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.

  17. Early and late endocrinologic complications of the hematopoetic stem cell transplantation performed for hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Murat Albayrak

    2012-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is usedfor various hematologic malignancies seen in childrenand adults. There may be several complications before,during, and after the HSCT. Just one of them is endocrinologiccomplications, since endocrine system (particularlythe pituitary gland, thyroid gland, adrenal glands, andgonads is highly sensitive against various stress. Chemotherapyand/or total body irradiation used as preparativeregimens and immunosuppressive agents (especiallycorticosteroids used for the graft-versus-host diseasecan cause hormonal disorders. Time elapsed after theHSCT, transplantation type (autologous or allogeneic,preparative regimen choice, age, and gender determinesthe complications. A multidisciplinary management containinga specialist of endocrinology for these patients ispreferred. In this report, we reviewed the endocrinologiccomplications that observed after the HSCT in childrenand adults referring to the recent literatures. J Clin ExpInvest 2012; 3(1: 149-156

  18. Emerging therapies targeting tumor vasculature in multiple myeloma and other hematologic and solid malignancies.

    Science.gov (United States)

    Podar, K; Anderson, K C

    2011-11-01

    Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti- VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical and clinical anti-cancer activity, they prolong overall survival of cancer patients for only months, followed by a restoration of tumor growth and progression. Therefore, there is a clear need to increase our understanding of tumor angiogenesis and the development of resistance. In this review we discuss up-to-date knowledge on mechanisms of tumor angiogenesis, and summarize preclinical and clinical data on existing and potential future anti-angiogenic agents and treatment strategies for Multiple Myeloma (MM) and other hematologic and solid malignancies.

  19. Advanced targeted, cell and gene therapy approaches for pediatric hematological malignancies: results and future perspectives

    Directory of Open Access Journals (Sweden)

    Chiara Francesca Magnani

    2013-04-01

    Full Text Available Despite the survival of pediatric patients affected by hematological malignancies being improved in the last 20 years by chemotherapy and hematopoietic stem cell transplantation (HSCT, a significant amount of patients still relapses. Treatment intensification is limited by toxic side effects and is constrained by the plateau of efficacy, while the pipeline of new chemotherapeutic drugs is running short. Therefore, novel therapeutic strategies are essential and researchers around the world are testing in clinical trials immune and gene therapy approaches as second-line treatments. The aim of this review is to give a glance at these novel promising strategies of advanced medicine in the field of pediatric leukemias. Results from clinical protocols using new targeted smart drugs, immunotherapy and gene therapy are summarized, and important considerations regarding the combination of these novel approaches with standard treatments to promote safe and long-term cure are discussed.

  20. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    Science.gov (United States)

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; Pmarrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; Ptransplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  1. All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

    Science.gov (United States)

    Karmali, Reem; Dalovisio, Andrew; Borgia, Jeffrey A; Venugopal, Parameswaran; Kim, Brian W; Grant-Szymanski, Kelly; Hari, Parameswaran; Lazarus, Hillard

    2015-03-01

    Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The present treatment and mechanism progress of arsenic trioxide in hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Zhi-Gang Zhao

    2016-01-01

    Arsenic trioide (ATO) is a kind of highly toxic substances and the main effective components of arsenic. ATO has been used medicinally for over 2400 years. Recent years, many studies have found that ATO has a significant efficacy on the acute promyelocytic leukemia (APL). To further explore the latest findings of research on the treatment of hematologic malignanies of ATO, this paper reviewed the development history of ATO, and summarized its mechanisms and clinical application in the treatment of hematologic malignancies. In addition, we want to provide new ideas for researches on the treatment of cancer of ATO.%三氧化二砷(ATO)是一种剧毒物质,又是中药砒霜的主要成分,人类用它作为药物治疗疾病已有2400多年的历史。近年来发现ATO对急性早幼粒细胞性白血病(APL)具有显著的疗效。为进一步了解ATO治疗血液系统恶性肿瘤作用的研究近况,本文回顾ATO的研发历史,并总结其在治疗血液恶性肿瘤中的作用机制及临床应用,以期为ATO治疗肿瘤方面的研究提供新的思路。

  3. Assessment of insertion techniques and complication rates of dual lumen central venous catheters in patients with hematological malignancies

    NARCIS (Netherlands)

    R.F.M. Jansen (Ruud); T. Wiggers (Theo); B.N. van Geel (Bert); W.L.J. van Putten (Wim)

    1990-01-01

    textabstractOne hundred and twenty-three dual lumen silicone rubber central venous catheters were inserted into 101 patients with hematological malignancies undergoing intensive treatment. There was a perioperative complication rate of 13%. Open and closed techniques for inserting the catheter were

  4. IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    蔡小矜

    2014-01-01

    Objective To explore the impact of interleukin-18(IL-18)single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation(allo-HSCT).Methods Single-nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis(PCR-SSP)in 93 recipients and their HLA matched sibling donors.Hematopoietic reconstitution,

  5. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    Science.gov (United States)

    Baron, Frédéric; Baker, Jennifer E; Storb, Rainer; Gooley, Theodore A; Sandmaier, Brenda M; Maris, Michael B; Maloney, David G; Heimfeld, Shelly; Oparin, Dmitrij; Zellmer, Eustacia; Radich, Jerald P; Grumet, F Carl; Blume, Karl G; Chauncey, Thomas R; Little, Marie-Térèse

    2004-10-15

    We analyzed the kinetics of donor engraftment among various peripheral blood cell subpopulations and their relationship to outcomes among 120 patients with hematologic malignancies given hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning consisting of 2 Gy total body irradiation (TBI) with or without added fludarabine. While patients rapidly developed high degrees of donor engraftment, most remained mixed donor/host chimeras for up to 180 days after HCT. Patients given preceding chemotherapies and those given granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts had the highest degrees of donor chimerism. Low donor T-cell (P = .003) and natural killer (NK) cell (P = .004) chimerism levels on day 14 were associated with increased probabilities of graft rejection. High T-cell chimerism on day 28 was associated with an increased probability of acute graft-versus-host disease (GVHD) (P = .02). Of 93 patients with measurable malignant disease at transplantation, 41 achieved complete remissions a median of 199 days after HCT; 19 of the 41 were mixed T-cell chimeras when complete remissions were achieved. Earlier establishment of donor NK-cell chimerism was associated with improved progression-free survival (P = .02). Measuring the levels of peripheral blood cell subset donor chimerisms provided useful information on HCT outcomes and might allow early therapeutic interventions to prevent graft rejection or disease progression.

  6. Hematology Glossary

    Science.gov (United States)

    ... of ASH ASH Meeting on Hematologic Malignancies Consultative Hematology Course ASH Meeting on Lymphoma Biology ASH Workshop on Genome Editing Publications Blood The Hematologist ASH Clinical News ASH Self-Assessment Program Hematology , ASH Education Program About Awards Membership ASH Foundation ...

  7. Tumefactive appearance of peripheral nerve involvement in hematologic malignancies: a new imaging association

    Energy Technology Data Exchange (ETDEWEB)

    Capek, Stepan [Mayo Clinic, Department of Neurosurgery, Rochester, Minnesota (United States); St. Anne' s University Hospital Brno, International Clinical Research Center, Brno (Czech Republic); Hebert-Blouin, Marie-Noelle [McGill University, Department of Neurologic Surgery, Montreal, Quebec (Canada); Puffer, Ross C.; Spinner, Robert J. [Mayo Clinic, Department of Neurosurgery, Rochester, Minnesota (United States); Martinoli, Carlo [Universita degli Studi di Genova, Department of Radiology, Genova (Italy); Frick, Matthew A.; Amrami, Kimberly K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2015-04-29

    In neurolymphomatosis (NL), the affected nerves are typically described to be enlarged and hyperintense on T2W MR sequences and to avidly enhance on gadolinium-enhanced T1WI. This pattern is highly non-specific. We recently became aware of a ''tumefactive pattern'' of NL, neuroleukemiosis (NLK) and neuroplasmacytoma (NPLC), which we believe is exclusive to hematologic diseases affecting peripheral nerves. We defined a ''tumefactive'' appearance as complex, fusiform, hyperintense on T2WI, circumferential tumor masses encasing the involved peripheral nerves. The nerves appear to be infiltrated by the tumor. Both structures show varying levels of homogenous enhancement. We reviewed our series of 52 cases of NL in search of this pattern; two extra outside cases of NL, three cases of NLK, and one case of NPLC were added to the series. We identified 20 tumefactive lesions in 18 patients (14 NL, three NLK, one NPLC). The brachial plexus (n = 7) was most commonly affected, followed by the sciatic nerve (n = 6) and lumbosacral plexus (n = 3). Four patients had involvement of other nerves. All were proven by biopsy: the diagnosis was high-grade lymphoma (n = 12), low-grade lymphoma (n = 3), acute leukemia (n = 2), and plasmacytoma (n = 1). We present a new imaging pattern of ''tumefactive'' neurolymphomatosis, neuroleukemiosis, or neuroplasmacytoma in a series of 18 cases. We believe this pattern is associated with hematologic diseases directly involving the peripheral nerves. Knowledge of this association can provide a clue to clinicians in establishing the correct diagnosis. Bearing in mind that tumefactive NL, NLK, and NPLC is a newly introduced imaging pattern, we still recommend to biopsy patients with suspicion of a malignancy. (orig.)

  8. Multiplex Reverse Transcription-Polymerase Chain Reaction for Simultaneous Screening of 29 Chromosomal Translocation in Hematologic Malignancies

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Multiplex reverse transcription-polymerase chain reaction (M-RT-PCR) has been proved to possess great clinical potential for simultaneous screening of 29 chromosomal translocations in acute leukemia. To evaluate the clinical value of M-RT-PCR in hematologic malignancies, bone marrow samples from 90 patients with various hematologic malignancies, including 25 acute myeloge nous leukemia (AML), 22 acute lymphoblastic leukemia (ALL), 27 chronic myelogenous leukemia (CML), 4 myeloproliferative diseases (MPD), 3 chronic lymphoblastic leukemia (CLL), 3 and 1 malignant histocytosis (MH) were subjected to both M-RT-PCR and chromosome karyotypic analysis. Some of cases were subjected to follow-up examination of M-RT-PCR during the period of ukemia. In our hand, 12 of 29chromosomal translocation transcripts including TEL/PDGFR, DEK/CAN, MLL/AF6, AML1/ETO,F9, BCR/ABL, MLL/MLL, PML/RARα, TLS/ERG, E2A/HLF, EVIl and HOXI1 were detected in 57 cases (63.3 %) of the 90 samples, which were in consistence with the results of karyore, M-RT-PCR had also shown good clinical relevance when used as an approach to detect minimal residual leukemia. We concluded that M-RT-PCR could be used as an effiy in the initial diagnosis of hematologic malignancies but also in subsequent monitor of minimal residual leukemia.

  9. Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases.

    Science.gov (United States)

    Ino, Kazuko; Nakase, Kazunori; Nakamura, Akiko; Nakamori, Yoshiki; Sugawara, Yumiko; Miyazaki, Kana; Monma, Fumihiko; Fujieda, Atsushi; Sugimoto, Yuka; Ohishi, Kohshi; Masuya, Masahiro; Katayama, Naoyuki

    2017-01-01

    Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.

  10. Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Serena Meraviglia

    2011-12-01

    Full Text Available The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.

  11. Randomized controlled trial comparing ciprofloxacin and cefepime in febrile neutropenic patients with hematological malignancies.

    Science.gov (United States)

    Yasuda, Takahiko; Suzuki, Ritsuro; Ishikawa, Yuichi; Terakura, Seitaro; Inamoto, Yoshihiro; Yanada, Masamitsu; Nagai, Hirokazu; Ozawa, Yukiyasu; Ozeki, Kazutaka; Atsuta, Yoshiko; Emi, Nobuhiko; Naoe, Tomoki

    2013-06-01

    Ciprofloxacin (CPFX) is a potential alternative in patients with febrile neutropenia (FN) because of its activity against Gram-negative organisms. We conducted a non-inferiority, open-label, randomized controlled trial comparing intravenous CPFX and cefepime (CFPM) for FN patients with hematological malignancies. Patients aged from 15 to 79 years with an absolute neutrophil count of response, and early toxicity were evaluated. Fifty-one episodes were included in this trial, and 49 episodes (CPFX vs. CFPM: 24 vs. 25) were evaluated. Treatment efficacy at day 7 was significantly higher in the CFPM group (successful clinical response: nine with CPFX and 19 with CFPM; p=0.007). The response was better in high-risk patients with neutrophil counts of ≤ 0.100 × 10(9/)l (p=0.003). The overall response during the study period was similar between the CPFX and CFPM groups (p=0.64). Adverse events were minimal, and all patients could continue the treatment. We could not prove the non-inferiority of CPFX in comparison with CFPM for the initial treatment of FN. CFPM remains the standard treatment of choice for FN. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Impact of Interstitial Pneumonia on the Survival and Risk Factors Analysis of Patients with Hematological Malignancy

    Directory of Open Access Journals (Sweden)

    Wei-Liang Chen

    2013-01-01

    Full Text Available Background. The emergence of interstitial pneumonia (IP in patients with hematological malignancy (HM is becoming a challenging scenario in current practice. However, detailed characterization and investigation of outcomes and risk factors on survival have not been addressed. Methods. We conducted a retrospective study of 42,584 cancer patients covering the period between 1996 and 2008 using the institutional cancer registry system. Among 816 HM patients, 61 patients with IP were recognized. The clinical features, laboratory results, and histological types were studied to determine the impact of IP on survival and identify the profile of prognostic factors. Results. HM patients with IP showed a significant worse survival than those without IP in the 5-year overall survival (P=0.027. The overall survival showed no significant difference between infectious pneumonia and noninfectious interstitial pneumonia (IIP versus nIIP (P=0.323. In a multivariate Cox regression model, leukocyte and platelet count were associated with increased risk of death. Conclusions. The occurrence of IP in HM patients is associated with increased mortality. Of interest, nIIP is a prognostic indicator in patients with lymphoma but not in patients with leukemia. However, aggressive management of IP in patients with HM is strongly advised, and further prospective survey is warranted.

  13. Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

    Directory of Open Access Journals (Sweden)

    P. J. Simpson-Haidaris

    2010-01-01

    Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

  14. Angiogenesis in hematological malignancy – Evaluated by dynamic contrast-enhanced MRI

    Directory of Open Access Journals (Sweden)

    Tiffany Ting-Fang Shih

    2016-12-01

    Full Text Available Bone marrow angiogenesis can be measured by DCE-MRI. DCE-MRI is an imaging technique that appears to provide quantitative and biologically relevant information related to tumor vasculature and angiogenesis, which can inform novel drug efficacy, monitor treatment response and act as an imaging biomarker to predict treatment outcome and survival in hematological malignant patients. Increased bone marrow perfusion as reflected by higher Peak value can independently predict adverse clinical outcome in patients with acute myeloid leukemia (AML. In addition, DCE-MRI derived data of bone marrow in AML patients at remission status provides useful information on clinical outcome of patients who might have relapse or not. Patients with a higher value for Kep at remission status would have shorter relapse-free duration and may need to undergo additional therapy. In multiple myeloma, DCE-MRI data correlate strongly with marrow tissue microvessel density. Studies identify high Amplitude values as a possible risk factor associated with the development of extra-medullary disease in multiple myeloma patients; these findings partly support the hypothesis that bone marrow angiogenesis may play role in the development of extra-medullary disease in multiple myeloma. DCE-MRI derived-parameters could serve as a guidance for the selection of optimal management plans, thereby contributing to the development of “personalized medicine” for patient.

  15. Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies.

    Science.gov (United States)

    Schulz-Kindermann, F; Mehnert, A; Scherwath, A; Schirmer, L; Schleimer, B; Zander, A R; Koch, U

    2007-06-01

    The aim of the study was to assess cognitive performance in patients with hematological malignancies before, and 3 months after, allogeneic hematopoietic stem cell transplant (HSCT). A consecutive sample of 39 patients was assessed before admission with a comprehensive neuropsychological test battery and health-related quality-of-life (HRQoL) questionnaires; 19 of these patients were retested around 100 days post HSCT. Test results were compared with normative data and revealed minimal differences at both time points in the level of group-means. One parameter - simple reaction time - was significantly worse (prolonged) at second measurement after HSCT. According to the definition of an impairment score (more than three impaired functions), 26% of patients were classified as impaired before as well as after HSCT. Neuropsychological test results did not vary systematically according to medical variables such as extent of pretreatment, graft-versus-host-disease (GvHD) and kind of conditioning protocol. As a dimension of HRQoL, self-rated cognitive function was in the normal range before and after HSCT. Significant correlations between HRQoL and neuropsychological parameters were related to symptom scales. This study showed impairments of neuropsychological performance for a subgroup of patients before and after allogeneic HSCT. Systematic effects of conditioning, medical variables or self-rated HRQoL could not be observed.

  16. Prevalence and Positive Correlates of Posttraumatic Stress Disorder Symptoms among Chinese Patients with Hematological Malignancies: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Li Liu

    Full Text Available Positive psychological constructs have been given increasing attention in research on the coping resources of cancer-related distresses. However, little research is available on posttraumatic stress disorder (PTSD in patients with hematological malignancies. The purposes of this study were to assess the prevalence of PTSD symptoms and to explore the associations of perceived social support (PSS, hope, optimism and resilience with PTSD symptoms among Chinese patients with hematological malignancies.A cross-sectional study was conducted during the period from July 2013 through April 2014. A total of 225 inpatients with hematological malignancies, which were eligible for the study, completed the Post-traumatic Stress Checklist-Civilian Version, Multidimensional Scale of Perceived Social Support, Adult Hope Scale, Life Orientation Scale-Revised, and Resilience Scale. Hierarchical regression analysis was performed to explore the correlates of PTSD symptoms.Overall, the prevalence of PTSD symptoms was 10.7%. Initially, PSS was negatively associated with PTSD symptoms (β = -0.248, P < 0.01. However, when positive psychological variables were added, optimism was negatively associated with PTSD symptoms (β = -0.452, P < 0.01, and gender had a significant effect on PTSD symptoms. Women were more vulnerable to these symptoms than men (β = 0.123, P < 0.05. When the analysis was performed separately by gender, only optimism showed a significantly negative association with PTSD symptoms in both men (β = -0.389, P < 0.01 and women (β = -0.493, P < 0.01.Some patients with hematological malignancies suffer from PTSD symptoms. The positive effects of PSS and optimism on PTSD symptoms suggest that an integrated approach to psychosocial intervention from both external and internal perspectives could have practical significance. Gender difference should be considered in developing potential interventions in reducing cancer-related PTSD symptoms.

  17. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

    OpenAIRE

    Nakamura Yukari; Motokura Toru; Sato Hiroyuki

    2007-01-01

    Abstract Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-...

  18. Predicting early post-chemotherapy adverse events in patients with hematological malignancies: a retrospective study.

    Science.gov (United States)

    Fei, Xiaoming; Lei, Fang; Zhang, Haifeng; Lu, Hua; Zhu, Yan; Tang, Yu

    2016-06-01

    The purpose of this study was to develop a mathematical model that predicts the definite adverse events following chemotherapy in patients with hematological malignancies (HMs). This is a retrospective cohort study including 1157 cases with HMs. Firstly, we screened and verified the independent risk factors associated with post-chemotherapy adverse events by both univariate and multivariate logistic regression analysis using 70 % of randomly selected cases (training set). Secondly, we proposed a mathematical model based on those selected factors. The calibration and discrimination of the model were assessed by Hosmer-Lemeshow (H-L) test and area under the receiver operating characteristic (ROC) curve, respectively. Lastly, the predicative power of this model was further tested in the remaining 30 % of cases (validation set). Our statistical analysis indicated that liver dysfunction (OR = 2.164), active infection (OR = 3.619), coagulation abnormalities (OR = 4.614), intensity of chemotherapy (OR = 10.001), acute leukemia (OR = 2.185), and obesity (OR = 1.604) were independent risk factors for post-chemotherapy adverse events in HM patients (all P point, the sensitivity and specificity of this predictive model in validation sets was 72.7 and 87.4 %, respectively. Furthermore, this proposed model's positive predictive value, negative predictive value, and consistency rate were 87.3, 73.0 and 80.0 %, respectively. Our study indicated that this six risk factor-based mathematical model is accurate and sufficient enough to predict definite post-chemotherapy adverse events in a HM patient and it may aid clinicians to optimize treatment for a HM patient.

  19. Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies.

    Science.gov (United States)

    Herold, Nikolas; Rudd, Sean G; Ljungblad, Linda; Sanjiv, Kumar; Myrberg, Ida Hed; Paulin, Cynthia B J; Heshmati, Yaser; Hagenkort, Anna; Kutzner, Juliane; Page, Brent D G; Calderón-Montaño, José M; Loseva, Olga; Jemth, Ann-Sofie; Bulli, Lorenzo; Axelsson, Hanna; Tesi, Bianca; Valerie, Nicholas C K; Höglund, Andreas; Bladh, Julia; Wiita, Elisée; Sundin, Mikael; Uhlin, Michael; Rassidakis, Georgios; Heyman, Mats; Tamm, Katja Pokrovskaja; Warpman-Berglund, Ulrika; Walfridsson, Julian; Lehmann, Sören; Grandér, Dan; Lundbäck, Thomas; Kogner, Per; Henter, Jan-Inge; Helleday, Thomas; Schaller, Torsten

    2017-02-01

    The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment. Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient-derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.

  20. Clinical significance and frequency of Blastocystis hominis in Turkish patients with hematological malignancy.

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    Taşova Y

    2000-06-01

    Full Text Available The effect of Blastocystis hominis (B. hominis in both immunocompetent and immunocompromised subjects has been the subject of debate in recent years, mostly in response to its unknown pathogenicity and frequency of occurrence. We performed a non-randomised, open labelled, single institute study in our hospital in order to investigate the clinical significance and frequency of B. hominis in patients suffering from hematological malignancy (HM who displayed symptoms of gastrointestinal diseases during the period of chemotherapy-induced neutropenia. The presence and potential role of other intestinal inclusive of parasites were also studied. At least 3 stool samples from each of 206 HM patients with gastrointestinal complaints (the HM group were studied. These were compared with stool samples from a control group of 200 patients without HM who were also suffering from gastrointestinal complaints. Samples were studied with saline-lugol, formalin-ether, and trichome staining methods. Groups were comparable in terms of gender, age and type of gastrointestinal complaints. In the HM group, the most common parasite was B. hominis. In this group, 23 patients (13% had B. hominis, while in the control group only 2 patients (1% had B. hominis. This difference was statistically significant (P < 0.05. Symptoms were non-specific for B. hominis or other parasites in the HM group. The predominant symptoms in both groups were abdominal pain (87-89.5%, diarrhea (70-89.5%, and flatulence (74-68.4%. Although all patients with HM were symptom-free at the end of treatment with oral metranidazol (1,500 mg per day for 10 days 2 patients with HM had positive stool samples containing an insignificant number of parasites (< 5 cells per field. In conclusion, it appears that B. hominis is not rare and should be considered in patients with HM who have gastrointestinal complaints while being treated with chemotherapy. Furthermore, metranidazol appears to be effective in

  1. Colistin is relatively safe in hematological malignancies and hematopoietic stem cell transplantation patients.

    Science.gov (United States)

    Averbuch, D; Horwitz, E; Strahilevitz, J; Stepensky, P; Goldschmidt, N; Gatt, M E; Shapira, M Y; Resnick, I B; Engelhard, D

    2013-10-01

    Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin. Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.

  2. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

    Science.gov (United States)

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies. PMID:26029215

  3. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

    Directory of Open Access Journals (Sweden)

    Gianfranco ePittari

    2015-05-01

    Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  4. Disseminated toxoplasmosis in non-allografted patients with hematologic malignancies: report of two cases and literature review.

    Science.gov (United States)

    Scerra, S; Coignard-Biehler, H; Lanternier, F; Suarez, F; Charlier-Woerther, C; Bougnoux, M-E; Gilquin, J; Lecuit, M; Hermine, O; Lortholary, O

    2013-10-01

    Toxoplasmosis can be a severe opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), and also among solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) patients. Patients with low-grade or chronic hematologic malignancies are treated with increasing immunosuppressive regimens and, therefore, represent an emerging population at risk for opportunistic diseases. We report here two cases of disseminated toxoplasmosis occurring in non-allografted hematologic patients with chronic lymphoproliferations. A review of 44 cases from the literature reveals that toxoplasmosis occurs increasingly in indolent B cell lymphoproliferative disorders. Aggressive lymphoproliferations, adenosine analogs, autologous HSCT, and the absence of chemoprophylaxis are the main risk factors for opportunistic toxoplasmosis. The central nervous system is the main organ involved. Fever is only present in half of all cases. Latent Toxoplasma cysts reactivation (LTCR) is the most common, but primary infection occurs in about 20% of cases. Global mortality is over 50%.

  5. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Directory of Open Access Journals (Sweden)

    M J Pont

    Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

  6. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Science.gov (United States)

    Pont, M J; Honders, M W; Kremer, A N; van Kooten, C; Out, C; Hiemstra, P S; de Boer, H C; Jager, M J; Schmelzer, E; Vries, R G; Al Hinai, A S; Kroes, W G; Monajemi, R; Goeman, J J; Böhringer, S; Marijt, W A F; Falkenburg, J H F; Griffioen, M

    2016-01-01

    Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

  7. 64 multidetector CT findings of influenza A (H1N1) virus in patients with hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    El-Badrawy, Adel [Dept. of Radiology, Mansoura Faculty of Medicine, Mansoura (Egypt)], E-mail: adelelbadrawy@hotmail.com; Zeidan, Amany [Dept. of Thoracic Medicine, Mansoura Faculty of Medicine, Mansoura (Egypt); Ebrahim, Mohamed A. [Dept. of Medical Oncology, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2012-07-15

    Background. The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases. Immunocompromised patients are at increased risk for morbidity and mortality. MDCT is superior to radiography in showing the distribution of the disease. Purpose. To review the 64 multidetector CT thoracic findings of novel swine-origin influenza A (H1N1) virus in patients with hematologic malignancies. Material and Methods. This study included 12 patients (3 women, 9 men; mean age, 32.2 years). All patients proved to be infected with influenza A (H1N1) virus. The hematologic malignancies were acute myeloid leukemia (n = 8), chronic lymphocytic leukemia (n = 2), multiple myeloma (n = 1), and myelodysplastic syndrome (n = 1). All the patients underwent CT scanning using a 64 multidetector CT scanner. Chest CT scans were reviewed for ground-glass opacities (GGOs), consolidation, airway thickening/dilatation, nodules, mediastinal lymphadenopathy, and pleural effusion. Results. More than one CT finding was detected in every patient. Pulmonary affection was bilateral, more on the left side. The affections were mainly peribronchial. Airway wall thickening and dilatation were detected in all 12 patients, GGO in 9/12 patients, nodules in 6/12 patients, consolidation in 6/12 patients, hilar lymphadenopathy in 3/12 patients, and pleural effusion in 2/12 patients. Conclusion. Acute myeloid leukemia is the most common hematologic malignancy affected by influenza A (H1N1) virus. The left lung is affected more than the right one. The most common multidetector CT findings are unilateral or bilateral airway thickening and dilatation. Multidetector CT can be used for early and accurate assessment of pulmonary affection with influenza A H1N1 virus infection.

  8. Hematological Malignancies and Thrombophilia%血液恶性肿瘤与易栓症

    Institute of Scientific and Technical Information of China (English)

    朱琳; 阿孜古丽

    2015-01-01

    Objective To investigate the relationship between coagulation function and thrombophilia in hematological malignancies .Methods The hospital blood malignant tumor in 100 cases of patients ( group A myeloproliferative disease in 30 cases,20 cases of group B myeloma,lymphoma in group C 50 cases)in plas-ma prothrombin time(PT)was measured for and activated partial thromboplastin time (aPTT),thrombin time (TT),fibrin original(Fbg),D-dimer(D-D)compared with healthy subjects,and blood platelet count(BPC). Results Compared with the normal control group ,BPC difference was not statistically significant (P>0.05);the Fbg and D-D were higher than the normal control group (P0.05).The thrombosis incidence of A was 6/30(20%),B group was 2/20(10%),C group was 8/50(16%).Conclusion Blood clotting index should be observed in the blood ,and the abnormal increase of D-D should be on the alert for thrombosis .Appropriate further screening ,immediately take antico-agulation after confirmed .%目的探讨血液恶性肿瘤的凝血功能与易栓症的相关性。方法本院血液恶性肿瘤住院患者100例( A组骨髓增殖性疾病30例,B组骨髓瘤20例,C组淋巴瘤50例),测定其血浆中凝血酶原时间( PT),活化部分凝血酶时间(aPTT),凝血酶时间(TT),纤维蛋白原(Fbg),D二聚体(D-D)多项凝血功能指标及血小板计数(BPC),并与健康者对比。结果患者组较正常对照组的血小板数,差异无统计学意义( P>0.05);Fbg、D-D较正常对照组的检测值均高,差异有统计学意义(P<0.05)。患者组较正常对照组的PT,TT,aPTT差异无统计学意义(P>0.05)。各疾病组血栓发生率:A组骨髓增殖性疾病为6/30(20%);B组骨髓瘤为2/20(10%);C组淋巴瘤为8/50(16%);而对照组无血栓发生。结论血液恶性肿瘤应定期观测凝血指标,D二聚体异常增高者要警惕有血栓形成,

  9. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization

    Science.gov (United States)

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A.; de Haas, Masja; de Vooght, Karen M.K.; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C.V.; Hudig, Francisca; van der Bom, Johanna G.

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization. PMID:27634204

  10. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

    2016-08-15

    The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non-Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non-Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further.

  11. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

    Science.gov (United States)

    Camargo, Carolina de Quadros; Borges, Dayanne da Silva; de Oliveira, Paula Fernanda; Chagas, Thayz Rodrigues; Del Moral, Joanita Angela Gonzaga; Durigon, Giovanna Steffanello; Dias, Bruno Vieira; Vieira, André Guedes; Gaspareto, Patrick; Trindade, Erasmo Benício Santos de Moraes; Nunes, Everson Araújo

    2015-01-01

    Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

  12. Intensive serial biomarker profiling for the prediction of neutropenic fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study

    Directory of Open Access Journals (Sweden)

    Steven M. Chan

    2014-06-01

    Full Text Available Neutropenic fever (NF is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial meas- urements of nine biomarkers [C-reactive protein (CRP, protein C, interleukin (IL-6, IL-8, IL-10, IL-1β, tumor necrosis factor-α, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793.

  13. Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies.

    Science.gov (United States)

    Matsushita, Maiko; Yamazaki, Rie; Ikeda, Hideyuki; Kawakami, Yutaka

    2003-03-01

    PRAME (Preferentially expressed antigen of melanoma), highly expressed in various solid tumor cells and normal testis, was first isolated as a human melanoma antigen recognized by cytotoxic T cells (CTL). This gene was also expressed in some of the hematological malignancies, including acute myelogenous leukemia (AML) and multiple myeloma. We and others have extensively evaluated the PRAME expression in various hematological malignancies and demonstrated high expression of the PRAME gene in subsets of AML, chronic myelogenous leukemia, acute lymphocytic leukemia, lymphoma and multiple myeloma. In addition, we have demonstrated that PRAME was a useful marker for detection of minimal residual disease (MRD) in patients with leukemia, particularly those leukemias in which tumor specific markers are currently unavailable. Since PRAME was first identified as a tumor antigen recognized by T cells, the possibility that PRAME is a leukemia antigen recognized by T cells was evaluated, and it was found that PRAME-positive leukemia cell lines and fresh leukemia cells were susceptible to lysis by the PRAME-specific CTL. Five CTL epitopes associated with either HLA-A*0201 or HLA-A*2402 have recently been identified. It is, therefore, an attractive strategy to apply PRAME specific immunotherapy on patients with PRAME positive leukemia in MRD condition.

  14. Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

    Science.gov (United States)

    2011-01-01

    Background Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era. Method A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009. Results Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS. Conclusions Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS. PMID:21939544

  15. STAT3 mutations identified in human hematologic neoplasms induce myeloid malignancies in a mouse bone marrow transplantation model

    Science.gov (United States)

    Couronné, Lucile; Scourzic, Laurianne; Pilati, Camilla; Valle, Véronique Della; Duffourd, Yannis; Solary, Eric; Vainchenker, William; Merlio, Jean-Philippe; Beylot-Barry, Marie; Damm, Frederik; Stern, Marc-Henri; Gaulard, Philippe; Lamant, Laurence; Delabesse, Eric; Merle-Beral, Hélène; Nguyen-Khac, Florence; Fontenay, Michaëla; Tilly, Hervé; Bastard, Christian; Zucman-Rossi, Jessica; Bernard, Olivier A.; Mercher, Thomas

    2013-01-01

    STAT3 protein phosphorylation is a frequent event in various hematologic malignancies and solid tumors. Acquired STAT3 mutations have been recently identified in 40% of patients with T-cell large granular lymphocytic leukemia, a rare T-cell disorder. In this study, we investigated the mutational status of STAT3 in a large series of patients with lymphoid and myeloid diseases. STAT3 mutations were identified in 1.6% (4 of 258) of patients with T-cell neoplasms, in 2.5% (2 of 79) of patients with diffuse large B-cell lymphoma but in no other B-cell lymphoma patients (0 of 104) or patients with myeloid malignancies (0 of 96). Functional in vitro assays indicated that the STAT3Y640F mutation leads to a constitutive phosphorylation of the protein. STA21, a STAT3 small molecule inhibitor, inhibited the proliferation of two distinct STAT3 mutated cell lines. Using a mouse bone marrow transplantation assay, we observed that STAT3Y640F expression leads to the development of myeloproliferative neoplasms with expansion of either myeloid cells or megakaryocytes. Together, these data indicate that the STAT3Y640F mutation leads to constitutive activation of STAT3, induces malignant hematopoiesis in vivo, and may represent a novel therapeutic target in some lymphoid malignancies. PMID:23872306

  16. Evaluation of a nurse-led telephone follow-up clinic for patients with indolent and chronic hematological malignancies: a pilot study.

    Science.gov (United States)

    Overend, Aldyn; Khoo, Kong; Delorme, Michael; Krause, Vanessa; Avanessian, Ardashes; Saltman, David

    2008-01-01

    A physician/nurse collaborative team sought to determine whether a nurse-led telephone clinic (Teleclinic) could effectively and safely be used to follow patients with indolent and chronic hematological malignancies. Patients seen at their routine follow-up visit were assessed for eligibility for the Teleclinic, then referred to the pilot Teleclinic by their oncologist. Patients were interviewed by telephone by an oncology nurse experienced in hematologic malignancies. Fifty-three patients consented to participate in the pilot study. Following their Teleclinic interview, patients were asked to complete a "Subject Satisfaction Questionnaire" (SSQ). Overall patient satisfaction with the Teleclinic was high. It was determined that patients with low-grade and chronic hematological malignancies could be followed effectively and safely by an oncology nurse-led telephone clinic.

  17. Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

    Science.gov (United States)

    2016-10-24

    Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

  18. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

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    Nakamura Yukari

    2007-11-01

    Full Text Available Abstract Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3σ gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3σ were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. Results The expression levels of 14-3-3σ mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3σ mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3% and rarely in acute leukemia (3 of 35, 8.6%. 14-3-3σ protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3σ gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3σ. The expression levels of 14-3-3σ, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. Conclusion 14-3-3σ, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3σ expression in non-epithelial tumors in vivo. Since the significance of 14-3-3

  19. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

    Science.gov (United States)

    Motokura, Toru; Nakamura, Yukari; Sato, Hiroyuki

    2007-01-01

    Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3σ gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3σ were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. Results The expression levels of 14-3-3σ mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3σ mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3%) and rarely in acute leukemia (3 of 35, 8.6%). 14-3-3σ protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3σ gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3σ. The expression levels of 14-3-3σ, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. Conclusion 14-3-3σ, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3σ expression in non-epithelial tumors in vivo. Since the significance of 14-3-3σ overexpression is unknown even in

  20. The more, the less: age and chemotherapy load are predictive of poor stem cell mobilization in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    YANG Shen-miao; CHEN Huan; CHEN Yu-hong; ZHU Hong-hu; ZHAO Ting; LIU Kai-yan

    2012-01-01

    Background Intensive treatment such as autologous peripheral blood stem cell (PBSC) transplantation is an important therapeutic strategy in many hematologic malignancies.A number of factors have been reported to impact PBSC mobilization,but the predictive factors varied from one study to another.This retrospective study assessed our current mobilization and collection protocols,and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Methods Data of 64 consecutive patients with hematologic malignancies (multiple myeloma,n=22; acute leukemia,n=27; lymphoma,n=15) who underwent PBSC mobilization for over 1 year were analyzed.Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor (G-CSF) to mobilize PBSCs.Sixty patients received G-CSF followed by chemotherapy mobilizing regimens.Poor mobilization (PM) was defined as when ≤2.0×106 CD34+ cells/kg body weight were collected within three leukapheresis procedures.Results The incidence of PM at the first mobilization attempt was 19% (12/64).The PM group was older than the non-PM group (median age,51 vs.40 years; P=0.013).In univariate analysis,there were no significant differences in gender,diagnosis,and body weight between the PM and non-PM groups.A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen (P=0.019).Grade Ⅲ or Ⅳ hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy.Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups.In multivariate analysis,age (odds ratio (OR),9.536;P=-0.002) and number of previous chemotherapy courses (OR 3.132; P=0.024) were two independent negative predictive factors for CD34+ cell yield.PM patients could be managed well by remobilization.Conclusion Older age and a heavy load of previous chemotherapy are the negative

  1. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival.

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    Emmanuel Canet

    Full Text Available BACKGROUND: Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient's ability to receive optimal chemotherapy. DESIGN AND METHODS: To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI, we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%. RESULTS: According to RIFLE criteria, 137 (68.5% patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01 and a higher mortality rate (47.4% vs. 30.2%, P<0.01 than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI. CONCLUSION: AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.

  2. Diagnostic strategies for invasive fungal infections in patients with hematologic malignancies and hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Norkin, Maxim; Wingard, John R

    2013-08-01

    Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

  3. Hematologic emergencies

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    Daniele Vallisa

    2012-01-01

    Full Text Available In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis.

  4. Longitudinal Changes in Body Mass and Composition in Survivors of Childhood Hematologic Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation

    Science.gov (United States)

    Inaba, Hiroto; Yang, Jie; Kaste, Sue C.; Hartford, Christine M.; Motosue, Megan S.; Chemaitilly, Wassim; Triplett, Brandon M.; Shook, David R.; Pui, Ching-Hon; Leung, Wing

    2012-01-01

    Purpose To measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT). Patients and Methods Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores. Results Over a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v −0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell–depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026). Conclusion BMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors. PMID:23032628

  5. Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study.

    Science.gov (United States)

    Libert, Yves; Borghgraef, Cindy; Beguin, Yves; Delvaux, Nicole; Devos, Martine; Doyen, Chantal; Dubruille, Stéphanie; Etienne, Anne-Marie; Liénard, Aurore; Merckaert, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Straetmans, Nicole; Van Den Neste, Eric; Bron, Dominique; Razavi, Darius

    2017-03-18

    Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy. We assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non-novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail-Making, Digit Span and FCSR-IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT-Cog questionnaire. In novel and non-novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non-novel context. Older, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non-novel contexts. Copyright © 2017 John Wiley & Sons, Ltd.

  6. A Randomized Study Comparing the Efficacy of Three Hepatitis B Vaccine Induction Regimens in Adult Patients with Hematological Malignancies

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    Zübeyde Nur Özkurt

    2016-08-01

    Full Text Available Objective: Non-responsiveness to hepatitis B virus (HBV vaccines is not rare in hemato-oncological patients due to disease-associated or treatment-induced immune suppression. Although different strategies have been employed to improve the response rates, to date there is not an approved schedule for HBV immunization in patients with hematological malignancies. We designed a prospective randomized study to evaluate the efficacy of 3 different induction regimens for HBV vaccination. Materials and Methods: In the standard-dose (SD group, total vaccine dose delivered was 40 μg and patients were vaccinated with 20 μg at weeks 0 and 4. In the high-dose dose-intensive (HDDI group, total vaccine dose delivered was 80 μg and patients were vaccinated with 40 μg at weeks 0 and 4. In the high-dose time-intensive (HDTI group, total vaccine dose delivered was 80 μg and patients were vaccinated with 20 μg at weeks 0, 2, 4, and 6. Results: In a cohort of 114 patients, 38.6% responded to HBV vaccination. The response rate in the SD arm, HDDI arm, and HDTI arm was 26.2%, 29.7%, and 44.4%, respectively (p>0.05. Age was the only variable identified as having a negative impact on response. Conclusion: Short of achieving statistical significance, a higher response rate was observed in the HDTI arm. Therefore, this study supports a high-dose, time-intensive HBV vaccine induction regimen in patients with hematological malignancies who are not on chemotherapy.

  7. Results of the Cord Blood Transplantation Study (COBLT) : clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies

    NARCIS (Netherlands)

    Kurtzberg, Joanne; Prasad, Vinod K.; Carter, Shelly L.; Wagner, John E.; Baxter-Lowe, Lee Ann; Wall, Donna; Kapoor, Neena; Guinan, Eva C.; Feig, Stephen A.; Wagner, Elizabeth L.; Kernan, Nancy A.

    2008-01-01

    Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching

  8. Results of the Cord Blood Transplantation Study (COBLT) : clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies

    NARCIS (Netherlands)

    Kurtzberg, Joanne; Prasad, Vinod K.; Carter, Shelly L.; Wagner, John E.; Baxter-Lowe, Lee Ann; Wall, Donna; Kapoor, Neena; Guinan, Eva C.; Feig, Stephen A.; Wagner, Elizabeth L.; Kernan, Nancy A.

    2008-01-01

    Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching

  9. Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle

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    Hisataka Kobayashi

    2005-11-01

    Full Text Available Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging-based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd-labeled dendrimer nanoparticle (generation-6; ~220 kDa/f10 nm was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL. Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1-weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.

  10. Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

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    Zha, Yunfei; Li, Maojin [Renmin Hospital of Wuhan University, Wuhan (China); Yang, Jianyong [the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2010-04-15

    To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic myeloid leukemia (n = 7), and non-Hodgkin lymphoma (n = 2). Twenty subjects whose spinal MRI was normal, made up the control group. Peak enhancement percentage (E{sub max}), enhancement slope (ES), and time to peak (TTP) were determined from a time intensity curve (TIC) of lumbar vertebral bone marrow. A comparison between baseline and follow-up MR images and its histological correlation were evaluated in 10 patients. The infiltration grade of hematopoietic marrow with plasma cells was evaluated by a histological assessment of bone marrow. Differences in E{sub max}, ES, and TTP values between the control group and the patients with diffuse bone marrow infiltration were significant (t = -11.51, -9.81 and 3.91, respectively, p < 0.01). E{sub max}, ES, and TTP values were significantly different between bone marrow infiltration groups Grade 1 and Grade 2 (Z = -2.72, -2.24 and -2.89 respectively, p < 0.05). E{sub max}, ES and TTP values were not significantly different between bone marrow infiltration groups Grade 2 and Grade 3 (Z = -1.57, -1.82 and -1.58 respectively, p > 0.05). A positive correlation was found between E{sub max}, ES values and the histological grade of bone marrow infiltration (r = 0.86 and 0.84 respectively, p < 0.01). A negative correlation was found between the TTP values and bone marrow infiltration histological grade (r = -0.54, p < 0.01). A decrease in the E{sub max} and ES values was observed with increased TTP values after treatment in all of the 10 patients who responded to treatment (t

  11. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    Science.gov (United States)

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

  12. Recommendations for accreditation of laboratories in molecular biology of hematologic malignancies.

    Science.gov (United States)

    Flandrin-Gresta, Pascale; Cornillet, Pascale; Hayette, Sandrine; Gachard, Nathalie; Tondeur, Sylvie; Mauté, Carole; Cayuela, Jean-Michel

    2015-01-01

    Over recent years, the development of molecular biology techniques has improved the hematological diseases diagnostic and follow-up. Consequently, these techniques are largely used in the biological screening of these diseases; therefore the Hemato-oncology molecular diagnostics laboratories must be actively involved in the accreditation process according the ISO 15189 standard. The French group of molecular biologists (GBMHM) provides requirements for the implementation of quality assurance for the medical molecular laboratories. This guideline states the recommendations for the pre-analytical, analytical (methods validation procedures, quality controls, reagents), and post-analytical conditions. In addition, herein we state a strategy for the internal quality control management. These recommendations will be regularly updated.

  13. Benign and malignant hematological manifestations of chronic Hepatitis C virus infection

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    Shiksha Kedia

    2014-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection, that affects 3% of world′s population, is associated with several hematological manifestations mainly benign cytopenias, coagulopathy and lymphoproliferative diseases. Immune or non-immune-mediated thrombocytopenia is a major challenge in chronic HCV infected patients especially in the setting of an advanced liver disease, with average prevalence of nearly 24%. Although several treatment modalities such as steroids, intravenous immunoglobulin, splenectomy and immunosuppresants have been tried with some success, their efficacy is not impressive and can result in an increase in viral load or other thrombotic complications. Even though a recent phase 2 study has shown promising role of a platelet growth factor, eltrombopag, in boosting platelets counts prior to antiviral treatment, its use in pre-operative setting had unexpected complications. Unlike thrombocytopenia, anemia and neutropenia are more frequently seen in treated patients and are often the result of antiviral therapy. HCV infection also pre-disposes to lymphoproliferative diseases, mainly non-Hodking′s lymphomas, likely as a result of chronic antigenic stimulation and mutation of several genes involved in carcinogenesis. Understanding of the role of HCV infection in these conditions has therapeutic implications. Whereas antiviral therapy has shown therapeutic role in HCV-associated indolent lymphomas, monitoring of hepatic function and viral load is important in the management of diffuse large B-cell lymphoma in HCV-infected patients. Although our knowledge about the HCV infection and hematological manifestations has substantially grown in last few decades, further studies are important to advance our therapeutic approach.

  14. Hematologic toxicity of gemcitabine: a comparison between fixed-dose rate infusion and thirty-minute infusion in the treatment of malignancy

    Institute of Scientific and Technical Information of China (English)

    Chunyan Li; Li Chu; Hui Han; Xi Liu; Yuping Shen; Mantang Qiu; Qing Xu

    2012-01-01

    Objective: The aim of the study was to compare the hematologic toxicity of gemcitabine between fixed-dose rate (FDR) infusion and 30-minute standard infusion in the treatment of malignancy. Methods: The 25 malignancy patients confirmed by histopathology or cytology received single-agent gemcitabine or gemcitabine in combination with other chemo-therapeutic agents. These patients were randomly divided into gemcitabine 1000 mg/m2 on d1, d8 at a rate of 10 mg/m2/min arm (FDR arm) or 30 min arm (standard arm), every 21 days one cycle. Hematologic toxicity was evaluated at the end of each cycle. Results: The 13 of 25 patients received gemcitabine FDR therapy, a total of 28 cycles was completed, and 32 cycles in the others (12 of 25 patients) with the standard arm. All patients were evaluable for hematologic toxicity. The result showed that the grades 3–4 leucopenia was significantly different between the two arms (14.3% vs 0, P 0.05, respectively) were observed between the two arms, no grade 4 of hemoglobin suppression was observed. Conclusion: Hematologic toxicity of gemcitabine therapy at a fixed-dose rate for malignancy is tolerable.

  15. Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond.

    Science.gov (United States)

    Katz, Ben-Zion; Herishanu, Yair

    2014-05-01

    Abstract During the past few decades, CD19 has been at the center of various scientific/translational endeavors to develop targeted therapeutics against B-cell malignancies. Due to the expression pattern of CD19 throughout the B-cell lineage, and on most B-cell malignancies, it became a preferred target for the development of experimental therapeutic agents during the first years of the monoclonal antibodies era. Successful preclinical experiments led to the first generation of clinical trials, based predominantly on toxin/anti-CD19 murine immunoconjugates. These, however, mostly failed due to poor biochemical design of the reagents, and the generation of human anti-murine antibodies. Modern anti-CD19 reagents are based on humanized anti-CD19 antibodies designed to attract components of the immune system, predominantly T-cells, to eliminate CD19+ target cells. These include, for example, modified anti-CD19 antibodies, and bispecific anti-CD19/CD3 antibodies. One of the most attractive approaches to target malignant B-cells is based on the introduction of chimeric antigen receptors (CARs) into patient derived T-cells. CARs are composed of extracellular recognition sequences derived from anti-CD19 antibodies, and intracellular signaling components that can foster T-cell activation. The novel anti-B-cell therapeutics have shown promising clinical effects against various B-cell malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), although expected side effects (e.g. significant immunosuppression) were also recorded. These novel successful anti-CD19 agents may have the potential to be used in other fields, such as autoimmunity.

  16. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies

    OpenAIRE

    2015-01-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes inc...

  17. Central Nervous System Disease in Hematological Malignancies: Historical Perspective and Practical Applications

    Science.gov (United States)

    Pui, Ching-Hon; Thiel, Eckhard

    2009-01-01

    Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use of cranial irradiation as central nervous system (CNS)-directed therapy, even in patients with high-risk presenting features, such as the presence of leukemia cells in the cerebrospinal fluid (even resulting from traumatic lumbar puncture), adverse genetic features, T-cell immunophenotype, and a large leukemia-cell burden. Current strategies for CNS-directed therapy involve effective systemic chemotherapy (eg, dexamethasone, high-dose methotrexate, intensive asparaginase, ifosfamide) and early intensification and optimization of intrathecal therapy. Options under investigation for the treatment of relapsed or refractory CNS leukemia in ALL patients include thiotepa and intrathecal liposomal cytarabine. CNS involvement in non-Hodgkin’s lymphoma (NHL) is associated with young age, advanced stage, number of extranodal sites, elevated lactate dehydrogenase, and International Prognostic Index score. Refractory CNS lymphoma in patients with NHL carries a poor prognosis, with a median survival of 2 to 6 months; the most promising treatment, autologous stem cell transplant, can extend median survival from 10 to 26 months. CNS prophylaxis is required during the initial treatment of NHL subtypes that carry a high risk of CNS relapse, such as B-cell ALL, Burkitt’s lymphoma, and lymphoblastic lymphoma. The use of CNS prophylaxis in the treatment of diffuse large B-cell lymphoma is controversial because of the low risk of CNS relapse (~5%) in this population. In this article, we review current and past practice of intrathecal therapy in ALL and NHL and the risk-models that aim to identify predictors of CNS relapse in NHL. PMID:19660680

  18. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies.

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    Eric Laille

    Full Text Available CC-486 (oral azacitidine is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK and pharmacodynamic (PD profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS, chronic myelomonocytic leukemia (CMML or acute myeloid leukemia (AML from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05 reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle, with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle.ClinicalTrials.gov NCT00528983.

  19. Prognostic role of microRNA-181a/b in hematological malignancies: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shenglong Lin

    Full Text Available BACKGROUND: Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes, and have prognostic value for patients with cancers. In recent years, the miR-181 family was found dysregulated in a variety of human cancers and significantly associated with clinical outcome of cancerous patients. MiR-181a and miR-181b (miR-181a/b were the most investigated members in the family. However, the results of miR-181a/b from different studies were inconsistent. Therefore, we performed a meta-analysis to summarize all the results from available studies, aiming to delineate the prognostic role of miR-181a/b in human cancers. METHODS: The identified articles were retrieved from the two main on-line databases, PubMed and EMBASE. We extracted and estimated the hazard ratios (HRs for overall survival (OS, which compared the high and low expression levels of miR-181a/b in patients of the available studies. Each individual HR was used to calculate the pooled HR. RESULTS: Eleven studies of 1252 patients were selected into the final meta-analysis after a strict filtering and qualifying process. Fixed model or random model method was chosen depending on the heterogeneity between the studies. The subgroup analysis showed that high expressed miR-181a/b could prolong OS in patients with hematological malignancies rather than low expression level (HR = 0.717, P<0.0001. But the expression of miR-181a/b was not significantly relative to OS in patients with various cancers (HR = 0.861, p = 0.356. CONCLUSION: Our study indicates that the expression level of miR-181a/b is significantly associated with OS in hematological malignancies and can be an important clinical prognostic factor for those patients.

  20. Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2016-07-15

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Inv(3)(q21q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

  1. Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies

    Science.gov (United States)

    2016-10-10

    Adult Solid Neoplasm; Childhood Solid Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm

  2. The kinetics of hematopoietic niche cytokines and their influence on mobilization efficacy and timing in patients with hematological malignancies.

    Science.gov (United States)

    Szmigielska-Kaplon, Anna; Krawczynska, Anna; Czemerska, Magdalena; Pluta, Agnieszka; Cebula-Obrzut, Barbara; Robak, Marta; Grzybowska-Izydorczyk, Olga; Szmigielska, Katarzyna; Robak, Tadeusz; Wierzbowska, Agnieszka

    2015-08-01

    The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM-1, VEGF, MMP-9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years. The group consisted of patients with multiple myeloma (26) and lymphoma (8). The mobilization procedures comprised chemotherapy and then G-CSF. Blood samples were collected before chemotherapy (N = 34) and on the day of the first apheresis (N = 26). Cytokines were evaluated with ELISA assay. We observed significant increase in VCAM-1 levels during mobilization. On contrary, VEGF and SDF levels decreased during mobilization procedure. The levels of MMP-9 were stable during mobilization. We divided patients according to baseline cytokines levels below and above median into "low" and "high" expressors. The group of VEGF "low" expressors had longer median time of G-CSF treatment before first apheresis than 'high' expressors. Baseline VEGF levels correlated adversely with duration of G-CSF treatment before first apheresis. Patients were also divided according to median cytokines levels at apheresis into "low" and "high" expressors. "High" VCAM-1 expressors had higher CD34+in peripheral blood as well as higher CD34+numbers collected during first apheresis than "low" expressors. In conclusion, the levels of niche cytokines change significantly during mobilization in patients with hematopoietic malignancies. Baseline VEGF can influence timing of mobilization. Higher VCAM-1 corresponds with higher mobilization efficacy.

  3. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2017-05-17

    Treated Myelodysplastic Syndromes; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Lymphoblastic Lymphoma

  4. Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies.

    Directory of Open Access Journals (Sweden)

    Maiko Matsushita

    Full Text Available The homeobox protein, PEPP2 (RHOXF2, has been suggested as a cancer/testis (CT antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2(271-279. The CTLs induced by PEPP2(271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2'-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2'-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients.

  5. Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4

    Directory of Open Access Journals (Sweden)

    Can Boğa

    2015-06-01

    Full Text Available This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.

  6. Bcl-2-family proteins and hematologic malignancies: history and future prospects.

    Science.gov (United States)

    Reed, John C

    2008-04-01

    BCL-2 was the first antideath gene discovered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.

  7. Therapeutic Challenges of Hepatic Mucormycosis in Hematologic Malignancy: A Case Report and Review of the Literature

    Science.gov (United States)

    Bernardo, Raffaele M.; Gurung, Ananta; Jain, Dhanpat; Malinis, Maricar F.

    2016-01-01

    Patient: Female, 58 Final Diagnosis: Hepatic mucormycosis Symptoms: Abdominal pain • fever Medication: Amphotericin • posaconazole Clinical Procedure: IR-guided aspiration Specialty: Infectious Diseases Objective: Rare disease Background: The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy-and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. Case Report: We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. Conclusions: Among patient with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy. PMID:27406045

  8. A Prospective Study of {sup 18}FDG-PET With CT Coregistration for Radiation Treatment Planning of Lymphomas and Other Hematologic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Terezakis, Stephanie A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schöder, Heiko [Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kowalski, Alexander; McCann, Patrick [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lim, Remy; Turlakov, Alla [Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gonen, Mithat [Department of Statistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Chris; Goenka, Anuj; Lovie, Shona [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-06-01

    Purpose: This prospective single-institution study examined the impact of positron emission tomography (PET) with the use of 2-[{sup 18}F] fluoro-2-deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP) on target volume definition in lymphoma. Methods and Materials: 118 patients underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and nuclear medicine physicians (NMPs) for 95 patients with positive PET scans. Treatment plans and dose-volume histograms were generated for CT-only and PET/CT for 95 evaluable sites. Paired t test statistics and Pearson correlation coefficients were used for analysis. Results: 70 (74%) patients had non-Hodgkin lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3 (3%) had other hematologic malignancies. Forty-three (45%) presented with relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The addition of PET increased GTV as defined by ROs in 38 patients (median, 27%; range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%; range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET-GTVs defined by ROs were larger than those defined by NMPs. On evaluation of clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of the PET-GTV defined by NMPs. Conclusions: Significant differences between the RO and NMP volumes were identified when PET was coregistered to CT for radiation planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable prescription dose in nearly all patients. However, given the potential for a marginal miss, consultation with an experienced PET

  9. Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

    Science.gov (United States)

    2014-12-09

    ; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelofibrosis; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome

  10. A role for peripherally inserted central venous catheters in the prevention of catheter-related blood stream infections in patients with hematological malignancies.

    Science.gov (United States)

    Sakai, Toshiro; Kohda, Kyuhei; Konuma, Yuichi; Hiraoka, Yasuko; Ichikawa, Yukari; Ono, Kaoru; Horiguchi, Hiroto; Tatekoshi, Ayumi; Takada, Kouichi; Iyama, Satoshi; Kato, Junji

    2014-12-01

    Central venous catheter-related blood stream infections (CR-BSIs) are a serious complication in patients with hematological malignancies. However, it remains unclear whether there is a difference in the rate of CR-BSI associated with the conventional type of central venous catheters (cCVCs) and peripherally inserted CVCs (PICCs) in such patients. To address this question, we retrospectively investigated the incidence of CR-BSIs associated with PICCs versus cCVCs in patients with hematological malignancies. We used PICCs in all consecutive patients requiring CVC placement between February 2009 and February 2013. We compared the CR-BSI rate in patients with PICCs with that in patients with cCVCs treated between September 2006 and January 2009 (control group). Eighty-four patients received PICCs and 85 received cCVCs. The most common reason for removal due to catheter-related complications was CR-BSI. The CR-BSI rate in the PICC group was significantly lower than that in the cCVC group (PICCs: 1.23/1000 catheter days; cCVCs: 5.30/1000 catheter days; P Catheter-related complications other than CR-BSIs occurred at an extremely low rate in the PICC group. The median catheter-related complication-free survival duration was significantly longer in the PICC group than in the cCVC group. Our study shows that PICCs are useful in patients with hematological malignancies.

  11. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A. (Institut Curie, Paris (France))

    1989-10-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients.

  12. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies.

    Science.gov (United States)

    Cumpston, Aaron; Caddell, Ryan; Shillingburg, Alexandra; Lu, Xiaoxiao; Wen, Sijin; Hamadani, Mehdi; Craig, Michael; Kanate, Abraham S

    2015-08-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

  13. Epigenetic inactivation of the MIR129-2 in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Wong Kwan-Yeung

    2013-02-01

    -519, inhibited cellular proliferation and enhanced cell death, with concomitant SOX4 mRNA downregulation. Conclusions MIR129-2 is a tumor suppressive microRNA frequently methylated in lymphoid but not myeloid malignancies, leading to reversible MIR129-2 silencing. In CLL, MIR129-2 methylation was associated with an inferior survival. In MM, MIR129-2 methylation might be acquired during progression from MGUS to symptomatic MM. In NHL, MIR129-2 methylation might collaborate with MIR124-1 and MIR203 methylation in lymphomagenesis.

  14. [Expression and Subcellular Distribution of Costimulatory Molecules B7-H1,B7-H3 and B7-H4 in Human Hematologic Malignancy Cell Lines].

    Science.gov (United States)

    Zhang, Wei; Wang, Jing; Wang, Yan-Fang; Zhu, Ming-Xia; Wan, Wen-Li; Li, Hai-Shen; Wu, Fei-Fei; Yan, Xin-Xing; Ke, Xiao-Yan

    2016-10-01

    To investigate the expression and subcellular distribution of costimulatory molecules B7-H1, B7-H3 and B7-H4 in human hematologic malignancy cell lines. The expression and subcellular distribution of B7-H1, B7-H3 and B7-H4 in 13 human hematologic malignancy cell lines were determined by RT-PCR, qPCR, Western blot and flow cytometry, the peripheral blood mononuclear cells (PB MNC) of 12 volunteers were used as control. The mRNA of B7-H1, B7-H3 and B7-H4 was widely expressed in PB MNC and hematologic malignancy cell lines, with a lower level of B7-H4. The mRNA expression of 3 molecules was highest in Maver, Z138, and HL-60, respectively, while among them the B7-H3 and B7-H4 had no expression in CZ1. The nuclear and cytoplasmic protein of 3 costimulatory molecules abnormally overexpressed only in hematologic malignancy cell lines, with the highest level in U937, Z138, and Raji, respectively, while the B7-H3 and B7-H4 had no expression in CZ1. There were differences among mRNA expression, nuclear and cytoplasmic protein expression of 3 molecules in cell lines derived from the same type of tumor, but the differences of expression in mRNA and protein levels were not exactly the same. The B7-H3 expression abundance in membrane localization was higher in U937, Maver and Z138, while the membrane protein of B7-H1 and B7-H4 had no or low expression in 13 cell lines. The mRNA expression of costimulatory molecules B7-H1, B7-H3 and B7-H4 can be widely detected. The protein level of 3 costimulatory molecules abnormally overexpressed only in hematologic malignancy cell lines, moreover the subcellular localizations mostly was found in nucleus and cytoplasm, while the membrane protein expresses in low level or had no expression. There are differences among the expression of 3 molecules in cell lines derived from the same type of tumor.

  15. Importance of epigenetic changes in cancer etiology, pathogenesis, clinical profiling, and treatment: what can be learned from hematologic malignancies?

    Science.gov (United States)

    Vecchio, Lorella; Seke Etet, Paul Faustin; Kipanyula, Maulilio John; Krampera, Mauro; Nwabo Kamdje, Armel Hervé

    2013-08-01

    Epigenetic alterations represent a key cancer hallmark, even in hematologic malignancies (HMs) or blood cancers, whose clinical features display a high inter-individual variability. Evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-based, clinical and experimental studies, we hypothesize that factors associated with risk for developing a HM, such as metabolic syndrome and chronic inflammation, trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Among others, signaling pathways associated with such risk factors include pro-inflammatory nuclear factor κB (NF-κB), and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways, which include signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.

  16. Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

    Science.gov (United States)

    2016-08-18

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Hodgkin Lymphoma; Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; Waldenstrom Macroglobulinemia

  17. RETREATMENT WITH FLUDARABINE AND CYCLOSPORINE FOR ONE CASE OF REFRACTORY PURE RED CELL APLASIA

    Institute of Scientific and Technical Information of China (English)

    Guang-sheng He; Xiang Zhang; De-pei Wu; Ai-ning Sun; Miao Miao; Xiu-li Wang; Zheng-ming Jin

    2008-01-01

    @@ MANY cases of pure red cell aplasia (PRCA) were mediated by over-function of immune cells, and responded well to immunosuppres-sive therapy.1 Sometimes refractory cases also arose. Fludara-bine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia (CLL) and other hematological malignancies.

  18. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.

    Science.gov (United States)

    Graux, Carlos; Sonet, Anne; Maertens, Johan; Duyster, Justus; Greiner, Jochen; Chalandon, Yves; Martinelli, Giovanni; Hess, Dagmar; Heim, Dominik; Giles, Francis J; Kelly, Kevin R; Gianella-Borradori, Athos; Longerey, Blandine; Asatiani, Ekaterine; Rejeb, Narmyn; Ottmann, Oliver G

    2013-09-01

    A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

    Directory of Open Access Journals (Sweden)

    Cheng MF

    2016-03-01

    Full Text Available Minfeng Cheng,* Huaying Gu,* Liangrong Zheng, Houliang Wang, Zhiyong Zhong, Shenglin Wen Department of Psychiatry, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized. Keywords: clozapine, neuroleptic malignant syndrome, withdrawal effect, schizophrenia

  20. The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

    Science.gov (United States)

    Chen, Y-K; Hou, H-A; Chow, J-M; Chen, Y-C; Hsueh, P-R; Tien, H-F

    2011-06-01

    The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

  1. c-Src activation through a TrkA and c-Src interaction is essential for cell proliferation and hematological malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Soo; Kim, Gyoung Mi; Choi, Yun-Jeong [Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840 (Korea, Republic of); Kim, Hye Joung [Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Kim, Yoo-Jin, E-mail: yoojink@catholic.ac.kr [Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Jin, Wook, E-mail: jinwo@gachon.ac.kr [Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Medical Center, Incheon 405-760 (Korea, Republic of)

    2013-11-15

    Highlights: •TrkA was mainly present in other types of leukemia including AML. •TrkA enhances the survival of leukemia by activation of PI3K/Akt pathway. •TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1. •TrkA acted as a key regulator of leukemogenesis and survival through c-Src activation. -- Abstract: Although the kinase receptor TrkA may play an important role in acute myeloid leukemia (AML), its involvement in other types of leukemia has not been reported. Furthermore, how it contributes to leukemogenesis is unknown. Here, we describe a molecular network that is important for TrkA function in leukemogenesis. We found that TrkA is frequently overexpressed in other types of leukemia such as acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) including AML. In addition, TrkA was overexpressed in patients with MDS or secondary AML evolving from MDS. TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1, and enhanced survival and proliferation of leukemia, which was correlated with activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway. Moreover, endogenous TrkA associated with c-Src complexes was detected in leukemia. Suppression of c-Src activation by TrkA resulted in markedly decreased expression of PLK-1 and Twist-1 via suppressed activation of Akt/mTOR cascades. These data suggest that TrkA plays a key role in leukemogenesis and reveal an unexpected physiological role for TrkA in the pathogenesis of leukemia. These data have important implications for understanding various hematological malignancies.

  2. Recommendations for the Treatment of Invasive Fungal Infections in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-1

    Directory of Open Access Journals (Sweden)

    Hamdi Akan

    2014-06-01

    Full Text Available The introduction of novel antifungal agents for the treatment of invasive fungal disease in hematological malignancies and also changing treatment strategies have had a great impact in managing affected patients. The medical literature includes some important clinical studies that are being used as evidence for guidelines. The problem with these studies and the guidelines is that they are not very easy to interpret, they include controversial issues, and they are not easy to apply to every patient or country. This paper was designed to critically show the main problems associated with these approaches and provide important information that will help Turkish doctors to adopt them in daily clinical practice.

  3. Efficacy and safety of itraconazole as empirical antifungal therapy in febrile neutropenic patients with hematologic malignancies: an open-lable, multicenter, observational trial in a Chinese cohort

    Institute of Scientific and Technical Information of China (English)

    CHENG Shu; ZHOU Jian-feng; ZOU Ping; HUANG Xiao-jun; JIN Jie; SHEN Zhi-xiang

    2011-01-01

    Background Invasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with hematological malignancy.Empirical antifungal therapy is widely used in practice due to the difficulty of pathogens determination and illness of the hosts.The aim of this study was to evaluate the efficacy and safety of itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematologic malignancies.Methods Two hundred and seventy-four patients with hematologic malignancies who had suspected fungal infections were enrolled in 18 centers across China between April 2008 and April 2009.Empirical antifungal therapy with intravenous itraconazole 200 mg twice daily was given for the first two days,followed by 200 mg once daily for the next 12 days.Oral itraconazole solution was sequential for follow-up therapy if necessary.Five composite end points were evaluated for the response,which was more restrictive and adopted for the first time in such study in China.Results The intent-to-treat analysis included data from 274 patients (full analysis set,FAS),of whom 248 were included as the per-protocol population (PPS).As the composite end point of five indices was concerned,the overall response rate was 43.4%.Seperately,defervescence was achieved in 90% of patients in which 55.5% occured during neutropenia.The mean time to defervescence was 2.71 days.Absence of breakthrough IFI during drug administration or within the first 7 days after study completion was observed in 71.5% of patients.Fifty-five point five percent patients with IFI at baseline was successfully treated.Ninety point five percent patients survived for at least 7 days after completing the study.PPS analysis revealed that the duration of neutropenia >10 days was a statistically significant negative predictor for the response.The withdrawal rate due to drug-related toxicity or lack of efficacy was 11.0%.The incidence of adverse events was 22.6%,in which 11

  4. Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study

    Science.gov (United States)

    Fouladi, Maryam; Stewart, Clinton F.; Olson, James; Wagner, Lars M.; Onar-Thomas, Arzu; Kocak, Mehmet; Packer, Roger J.; Goldman, Stewart; Gururangan, Sridharan; Gajjar, Amar; Demuth, Tim; Kun, Larry E.; Boyett, James M.; Gilbertson, Richard J.

    2011-01-01

    Purpose To estimate the maximum-tolerated dose (MTD), describe dose-limiting toxicities (DLTs), and characterize pharmacokinetic properties of MK-0752, a gamma secretase inhibitor, in children with refractory or recurrent CNS malignancies. Patients and Methods MK-0752 was administered once daily for 3 consecutive days of every 7 days at escalating dosages starting at 200 mg/m2. The modified continual reassessment method was used to estimate the MTD. A course was 28 days in duration. Pharmacokinetic analysis was performed during the first course. Expression of NOTCH and hairy enhancer of split (HES) proteins was assessed in peripheral-blood mononuclear cells (PBMCs) before and following treatment with MK-0752. Results Twenty-three eligible patients were enrolled: 10 males (median age, 8.1 years; range, 2.6 to 17.7 years) with diagnoses of brainstem glioma (n = 6), ependymoma (n = 8), medulloblastoma/primitive neuroectodermal tumor (n = 4), glioblastoma multiforme (n = 2), atypical teratoid/rhabdoid tumor (n = 1), malignant glioma (n = 1), and choroid plexus carcinoma, (n = 1). Seventeen patients were fully evaluable for toxicity. No DLTs occurred in the three patients enrolled at 200 mg/m2/dose. At 260 mg/m2/dose, DLTs occurred in two of six patients, both of whom experienced grade 3 ALT and AST. There were no grade 4 toxicities; non–dose-limiting grade 3 toxicities included hypokalemia and lymphopenia. Population pharmacokinetic values (% coefficient of variation) for MK-0752 were apparent oral clearance, 0.444 (38%) L/h/m2; apparent volume of distribution, 7.36 (24%) L/m2; and ka, 0.358 (99%) hr−1. Conclusion MK-0752 is well-tolerated in children with recurrent CNS malignancies. The recommended phase II dose using the 3 days on followed by 4 days off schedule is 260 mg/m2/dose once daily. PMID:21825264

  5. Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19

    Science.gov (United States)

    2016-01-26

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  6. PROPOFOL-FENTANYL VERSUS PROPOFOL ALONE FOR LUMBAR PUNCTURE SEDATION IN CHILDREN WITH ACUTE HEMATOLOGIC MALIGNANCIES: PROPOFOL DOSING AND ADVERSE EVENTS

    Science.gov (United States)

    Hollman, Gregory A.; Schultz, Meredith M; Eickhoff, Jens C; Christenson, Devon K

    2011-01-01

    Objective We sought to determine whether the combination of propofol and fentanyl results in lower propofol doses and fewer adverse cardiopulmonary events than propofol and placebo for lumbar puncture (LP) in children with acute hematologic malignancies. Design Randomized, controlled, double blind, crossover study. Setting Pediatric Sedation Program Patients Children with acute leukemia or lymphoma receiving sedation for LP. Interventions Each patient received two sedations in random order, one with propofol/placebo and one with propofol/fentanyl. The study investigator and patient/parent were blinded to placebo or fentanyl. Data collected included patient age and diagnosis, propofol dose and adverse events. Adverse events included oxygen saturation propofol was 5.05 mg/kg (range 2.4–10.2 mg/kg) for propofol/placebo versus 3.00 mg/kg (range 1.4–10.5 mg/kg) for propofol/fentanyl (p propofol/placebo compared to 6 of 22 (18.2%) propofol/fentanyl (p= 0.02). The most common adverse event was hypotension. Conclusions The combination of propofol and fentanyl versus propofol alone for LP sedation in children with acute hematologic malignancies resulted in lower propofol doses and fewer adverse events. PMID:18838923

  7. New drugs and allogeneic hematopoietic stem cell transplantation for hematological malignancies: do they have a role in bridging, consolidating or conditioning transplantation treatment?

    Science.gov (United States)

    Patriarca, Francesca; Giaccone, Luisa; Onida, Francesco; Castagna, Luca; Sarina, Barbara; Montefusco, Vittorio; Mussetti, Alberto; Mordini, Nicola; Maino, Elena; Greco, Raffaella; Peccatori, Jacopo; Festuccia, Moreno; Zaja, Francesco; Volpetti, Stefano; Risitano, Antonio; Bassan, Renato; Corradini, Paolo; Ciceri, Fabio; Fanin, Renato; Baccarani, Michele; Rambaldi, Alessandro; Bonifazi, Francesca; Bruno, Benedetto

    2017-07-01

    Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered: This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy. Expert opinion: After having been used as single agent salvage treatments in relapsed patients after allo-SCT or in combination with donor lymphocyte infusions, many new drugs have also been safely employed before allo-SCT as a bridge to transplantation or after it as planned consolidation/maintenance. This era of new drugs has opened new important opportunities to 'smartly' combine 'targeted drugs and cell therapies' in new treatment paradigms that may lead to higher cure rates or longer disease control in patients with hematological malignancies.

  8. LKB1/AMPK/mTOR signaling pathway and hematological malignancies%LKB1/AMPK/mTOR信号通路与血液肿瘤

    Institute of Scientific and Technical Information of China (English)

    陈岚; 任立红

    2013-01-01

    Hematological malignancies have become a serious threaten to children' s health,and its incidence increases yearly.Research studies have found that LKB 1/AMPK/mTOR signaling pathway plays an important role in several types of cancerous cells,including human breast cancer,prostate cancer,hepatic carcinoma,lung cancer and lymphoma.The LKB1/AMPK/mTOR axis as a new target has become a interesting topic.This review aims to discuss the relationship between LKB1/AMPK/mTOR and hematological malignancies.%血液肿瘤已成为严重威胁儿童生命的主要疾病之一,其发病率逐年升高.随着研究的不断深入,LKB1/AMPK/mTOR信号转导通路在多种常见肿瘤如乳腺癌、前列腺癌、肝癌、肺癌及淋巴瘤等的研究中凸现出日益重要的作用,并为肿瘤的治疗提供了新的靶点,成为目前研究的热点.现就LKB1/AMPK/mTOR信号通路的组成及其与血液肿瘤的关系以及分子机制作一综述.

  9. No effect of HLA-C mismatch after allogeneic hematopoietic stem cell transplantation with unrelated donors and T-cell depletion in patients with hematological malignancies.

    Science.gov (United States)

    Magalhaes, Isabelle; Uhlin, Michael; Schaffer, Marie; Sundin, Mikael; Hauzenberger, Dan; Remberger, Mats; Mattsson, Jonas

    2017-08-01

    HLA-C mismatch in unrelated donor's hematopoietic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA-C mismatch in the context of HSCT combined with in vivo T-cell depletion remains unclear. We therefore performed a single-center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo-HSCT, who underwent T-cell depletion. The majority of the patients (n=276) received a HLA-A, HLA-B, HLA-DRB1-matched graft that were either also HLA-C matched (n=260), or patients with the permissive HLA-C*03:03/03:04 mismatch (n=16), while the remaining patients (n=95) received a HLA-C-mismatched graft (excluding HLA-C*03:03/03:04 mismatches). We did not observe any significant differences between the HLA-C-matched patients (including the permissive HLA-C*03:03/03:04 mismatch) and the HLA-C-mismatched patients regarding cumulative proportion surviving, graft failure, relapse-free survival, relapse, or acute graft-versus-host disease. Our data suggest that in the context of high dose T lymphocyte-depleting agents, HLA-C matching is not essential for patients with hematological malignancies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2015-12-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Ageing, exposure to pollution, and interactions between climate change and local seasons as oxidant conditions predicting incident hematologic malignancy at KINSHASA University clinics, Democratic Republic of CONGO (DRC).

    Science.gov (United States)

    Nkanga, Mireille Solange Nganga; Longo-Mbenza, Benjamin; Adeniyi, Oladele Vincent; Ngwidiwo, Jacques Bikaula; Katawandja, Antoine Lufimbo; Kazadi, Paul Roger Beia; Nzonzila, Alain Nganga

    2017-08-23

    The global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC). This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM. This hospital-based prospective cohort study was conducted at Kinshasa University Clinics in DR Congo. A total of 105 black African adult patients with anaemia between 2009 and 2016 were included. HM was confirmed by morphological typing according to the French-American-British (FAB) Classification System. Gender, age, exposure to traffic pollution and garages/stations, global climate variability (El Nino and La Nina), and local climate (dry and rainy seasons) were potential independent variables to predict incident HM using Cox regression analysis and Kaplan Meier curves. Out of the total 105 patients, 63 experienced incident HM, with an incidence rate of 60%. After adjusting for gender, HIV/AIDS, and other bio-clinical factors, the most significant independent predictors of HM were age ≥ 55 years (HR = 2.4; 95% CI 1.4-4.3; P = 0.003), exposure to pollution and garages or stations (HR = 4.9; 95% CI 2-12.1; P types included acute myeloid leukaemia (28.6% n = 18), multiple myeloma (22.2% n = 14), myelodysplastic syndromes (15.9% n = 10), chronic myeloid leukaemia (15.9% n = 10), chronic lymphoid leukaemia (9.5% n = 6), and acute lymphoid leukaemia (7.9% n = 5). After adjusting for confounders using Cox regression analysis, age ≥ 55 years, exposure to pollution, combined local dry season + La Nina and combined local dry season + El Nino were the most significant predictors of

  12. Microarray gene expression analysis to evaluate cell type specific expression of targets relevant for immunotherapy of hematological malignancies

    NARCIS (Netherlands)

    M.J. Pont (Margot); M.W. Honders; A.N. Kremer; C. van Kooten (Cees); C. Out; P.S. Hiemstra (Pieter); H.C. De Boer; M.J. Jager (Martine); E. Schmelzer; R.G.J. Vries (Robert); A.S. Al Hinai; W.G. Kroes (W.); R. Monajemi (Ramin); J.J. Goeman (Jelle); S. Böhringer (Stefan); W.A.F. Marijt; J.H.F. Falkenburg (Frederik); M. Griffioen

    2016-01-01

    textabstractCellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However,

  13. Microarray gene expression analysis to evaluate cell type specific expression of targets relevant for immunotherapy of hematological malignancies

    NARCIS (Netherlands)

    M.J. Pont (Margot); M.W. Honders; A.N. Kremer; C. van Kooten (Cees); C. Out; P.S. Hiemstra (Pieter); H.C. De Boer; M.J. Jager (Martine); E. Schmelzer; R.G.J. Vries (Robert); A.S. Al Hinai; W.G. Kroes (W.); R. Monajemi (Ramin); J.J. Goeman (Jelle); S. Böhringer (Stefan); W.A.F. Marijt; J.H.F. Falkenburg (Frederik); M. Griffioen

    2016-01-01

    textabstractCellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, de

  14. Palliative Care Office Hours for Patients with Hematologic Malignancies: An Innovative Model for Symptom Management and Education.

    Science.gov (United States)

    Foxwell, Anessa M; Moyer, Mary E; Casarett, David J; O'Connor, Nina R

    2017-10-01

    Palliative care programs are experiencing rapid growth, with demand for consults surpassing staffing. Innovative models are needed to equip nonpalliative care providers to manage basic palliative care issues. To develop a novel program of palliative care office hours for hematologic oncology advanced practice providers, and to evaluate its impact on palliative care consult volume and composition. A palliative care nurse practitioner or pharmacist was available for weekday office hours to all inpatient hematologic oncology advanced practice providers at an academic medical center to offer advice on pain, nonpain symptoms, and psychosocial distress. A retrospective study looking at outcome measures after six months of office hour utilization and palliative care consults from the hematologic oncology services. Palliative care office hours had a mean duration of 16 minutes per day (range 5 to 55). A mean of 11 patients were discussed per week (range 4 to 20). Pain, nausea, and anxiety were the issues most frequently raised. Of 299 patients discussed during office hours, 44 (14.7%) subsequently required a full palliative care consult. Overall, palliative care consults from the hematologic oncology services decreased from 19.6% to 10.2% of admissions (87/445 vs. 61/594, p Office hours are an efficient way to address palliative care needs when demand for palliative care consults exceeds capacity. Office hours may serve an educational function as well, enabling primary teams to manage basic palliative care issues with increasing independence over time.

  15. Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies

    Science.gov (United States)

    2017-04-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  16. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies

    OpenAIRE

    Pont, M. J.; Honders, M.W.; Kremer, A. N.; van Kooten, C.; C Out; Hiemstra, P. S.; de Boer, H. C.; Jager, M J; Schmelzer, E; Vries, R.G.; A S Al Hinai; Kroes, W. G.; Monajemi, R.; Goeman, J.J.; Böhringer, S

    2016-01-01

    Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimat...

  17. Pharmacoutilization of epoetins in naïve patients with hematological malignancies in an unselected Italian population under clinical practice setting: a comparative analysis between originator and biosimilars

    Science.gov (United States)

    Perrone, Valentina; Saragoni, Stefania; Buda, Stefano; Broccoli, Alessandro; Degli Esposti, Luca

    2016-01-01

    Aim The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in naïve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (ΔHb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean ± standard deviation (SD) age was 62.5±14.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8±11.8 years). The mean ± SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6±1.1 g/dL) compared to those who started with a reference product (10.1±2.1 g/dL). No significant differences in ΔHb were observed between biosimilar and originator groups during the followup period. The mean ± SD cost per patient was €667.98±573.93 and €340.85±235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion Our study showed that the use of

  18. Rapid detection of DNMT3A R882 mutations in hematologic malignancies using a novel bead-based suspension assay with BNA(NC probes.

    Directory of Open Access Journals (Sweden)

    Velizar Shivarov

    Full Text Available Mutations in the human DNA methyl transferase 3A (DNMT3A gene are recurrently identified in several hematologic malignancies such as Philadelphia chromosome-negative myeloproliferative neoplasms (MPN, myelodysplastic syndromes (MDS, MPN/MDS overlap syndromes and acute myeloid leukemia (AML. They have been shown to confer worse prognosis in some of these entities. Notably, about 2/3 of these mutations are missense mutations in codon R882 of the gene. We aimed at the development and validation of a novel easily applicable in routine practice method for quantitative detection of the DNMT3A p.R882C/H/R/S mutations bead-based suspension assay. Initial testing on plasmid constructs showed excellent performance of BNA(NC-modified probes with an optimal hybridization temperature of 66°C. The method appeared to be quantitative and showed sensitivity of 2.5% for different mutant alleles, making it significantly superior to direct sequencing. The assay was further validated on plasmid standards at different ratios between wild type and mutant alleles and on clinical samples from 120 patients with known or suspected myeloid malignancies. This is the first report on the quantitative detection of DNMT3A R882 mutations using bead-based suspension assay with BNA(NC-modified probes. Our data showed that it could be successfully implemented in the diagnostic work-up for patients with myeloid malignancies, as it is rapid, easy and reliable in terms of specificity and sensitivity.

  19. The research development of Chimeric Antigen Receptor T-cells in hematological malignancies%CAR -T 细胞治疗在血液系统恶性肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    桑秀莉; 史策(综述); 周晋(审校)

    2016-01-01

    In recent years,chimeric antigen receptor T -cells(CAR-T cells)therapy becomes the new rapid development of adoptive tumor immunotherapy .Its main characteristic is to identify specific T cell receptor of tumor antigen by genetic engineering modification and give its targeting ,killing and persistent treatment .The CAR-T was mentioned for the first time in 1989,and has developed to the fourth generation .CD19-CAR-T treatment technique shows activity in phase I clinical trials of multiple research centers .CAR-T therapy is ex-pected as a new way to cure relapse/refractory hematological malignancies .%嵌合抗原受体T( CAR-T)细胞是近年来迅速发展的肿瘤过继性免疫治疗新手段。其主要特点是通过基因工程改造获得识别肿瘤抗原特异性受体的T细胞并赋予其靶向性、杀伤性及持久性的治疗方法。1989年首次提出CAR-T,现已经发展到第四代,且多研究中心对CD19-CAR-T细胞治疗技术进行了Ⅰ期临床研究显示出活性。 CAR-T疗法是目前有望治愈复发难治性血液肿瘤的新方法。

  20. T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies.

    Science.gov (United States)

    Vadillo, Eduardo; Dorantes-Acosta, Elisa; Pelayo, Rosana; Schnoor, Michael

    2017-08-15

    T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% and 25% of total childhood and adult ALL cases, respectively. During T-ALL, patients are at risk of organ infiltration by leukemic T-cells. Infiltration is a major consequence of disease relapse and correlates with poor prognosis. Transendothelial migration of leukemic cells is required to exit the blood stream into target organs. While mechanisms of normal T-cell transmigration are well known, the mechanisms of leukemic T-cell extravasation remain elusive; but involvement of chemokines, integrins and Notch signaling play critical roles. Here, we summarize current knowledge about molecular mechanisms of leukemic T-cell infiltration with special emphasis on the newly identified subtype early T-cell-progenitor (ETP)-ALL. Furthermore, we compare the extravasation potential of T-ALL cells with that of other hematologic malignancies such as B-ALL and acute myeloid leukemia (AML). Copyright © 2017. Published by Elsevier Ltd.

  1. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3).

    Science.gov (United States)

    Skiada, Anna; Lanternier, Fanny; Groll, Andreas H; Pagano, Livio; Zimmerli, Stephan; Herbrecht, Raoul; Lortholary, Olivier; Petrikkos, George L

    2013-04-01

    Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).

  2. Research update of pharmacogenomics for hematologic malignancies%血液肿瘤相关药物基因组学研究和应用进展

    Institute of Scientific and Technical Information of China (English)

    周枫叶; 张阳; 刘红星

    2016-01-01

    由于多数血液肿瘤治疗药物不良反应多、治疗窗窄、个体差异大,正确合理地应用抗肿瘤药物有助于降低死亡率、复发率和不良反应发生率。近年来在药物基因组学检测指导下的个体化治疗被日益重视。药物基因组学的主要研究对象包括药物代谢酶、药物转运体及药物作用靶标等相关基因的多态性或突变对药代动力学、药效动力学的影响。本文就血液肿瘤治疗相关的药物基因组学的研究和应用进展进行综述。%Considering the adverse drug reactions, narrow therapeutic window and individual variance, reasonable use of anticancer drugs will help to reduce mortality, relapse rate and incidence of adverse drug reactions of hematological malignancies. The concept of “personalized medicine” under the guidance of pharmacogenomics detection is increasing valued in recent years. Pharmacogenomics focuses on gene polymorphisms and mutations of drug metabolizing enzymes, drug transporters and therapeutic targets and its impact on pharmacokinetics/pharmacodynamics. This paper summarized progress on the research and application of pharmacogenomics in hematological malignancies.

  3. Efficacy of Oral Cryotherapy on Oral Mucositis Prevention in Patients with Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

    2015-01-01

    Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT. PMID:26024220

  4. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT. The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN use, and length of hospital stay.Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99 and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25. In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively. However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively.Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

  5. Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study.

    Science.gov (United States)

    Jeong, Seong Hyun; Kim, Dae Young; Jang, Jun Ho; Mun, Yeung-Chul; Choi, Chul Won; Kim, Sung-Hyun; Kim, Jin Seok; Park, Joon Seong

    2016-01-01

    Micafungin, a clinically important echinocandin antifungal drug, needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds. A prospective randomized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies. The antifungal drug (micafungin 100 mg or itraconazole 200 mg IV once daily) was given for high fever that was sustained despite the administration of appropriate antibiotics. Treatment success was determined by composite end points based on breakthrough invasive fungal infection (IFI), survival, premature discontinuation, defervescence, and treatment of baseline fungal infection. Duration of fever, hospital stay, and overall survival (OS) were studied. A total of 153 patients were randomized to receive micafungin or itraconazole. The overall success rate was 7.1 % point higher in the micafungin group (64.4 vs. 57.3 %, p = 0.404), satisfying the statistical criteria for the non-inferiority of micafungin. The duration of fever and hospital stay were significantly shorter in the micafungin group (6 vs. 7 days, p = 0.014; 22 vs. 27 days, p = 0.033, respectively). Grade 3 adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase levels (2 vs. 4), electrolyte imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred in 7 and 13 patients in the micafungin (10.4 %) and itraconazole (18.8 %) groups, respectively. Micafungin, when compared with itraconazole, had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies. In addition, it showed superior effect on shortening the hospital stay.

  6. Detection of Aspergillus flavus and A. fumigatus in Bronchoalveolar Lavage Specimens of Hematopoietic Stem Cell Transplants and Hematological Malignancies Patients by Real-Time Polymerase Chain Reaction, Nested PCR and Mycological Assays.

    Science.gov (United States)

    Zarrinfar, Hossein; Mirhendi, Hossein; Fata, Abdolmajid; Khodadadi, Hossein; Kordbacheh, Parivash

    2015-01-01

    Pulmonary aspergillosis (PA) is one of the most serious complications in immunocompromised patients, in particular among hematopoietic stem cell transplants (HSCT) and patients with hematological malignancies. The current study aimed to evaluate the incidence of PA and utility of molecular methods in HSCT and patients with hematological malignancies, four methods including direct examination, culture, nested polymerase chain reaction (PCR) and real-time PCR were performed on bronchoalveolar lavage (BAL) specimens in Tehran, Iran. During 16 months, 46 BAL specimens were obtained from individuals with allogeneic HSCT (n = 18) and patients with hematological malignancies (n = 28). Direct wet mounts with 20% potassium hydroxide (KOH) and culture on mycological media were performed. The molecular detection of Aspergillus fumigatus and A. flavus was done by amplifying the conserved sequences of internal transcribed spacer 1 (ITS1) ribosomal DNA by nested-PCR and the β-tubulin gene by TaqMan real-time PCR. Seven (15.2%) out of 46 specimens were positive in direct examination and showed branched septate hyphae; 11 (23.9%) had positive culture including eight (72.7%) A. flavus and three (27.3%) A. fumigatus; 22 (47.8%) had positive nested-PCR and eight (17.4%) had positive real-time PCR. The incidence of invasive pulmonary aspergillosis (IPA) in these patients included proven IPA in 1 (2.2%), probable IPA in 10 (21.7%), possible IPA in 19 (41.3%) and not IPA in 16 cases (34.8%). The incidence of IPA in allogeneic HSCT and patients with hematological malignancies was relatively high and A. flavus was the most common cause of PA. As molecular methods had higher sensitivity, it may be useful as screening methods in HSCT and patients with hematological malignancies, or to determine when empirical antifungal therapy can be withheld.

  7. Pharmacoutilization of epoetins in naïve patients with hematological malignancies in an unselected Italian population under clinical practice setting: a comparative analysis between originator and biosimiliars

    Directory of Open Access Journals (Sweden)

    Perrone V

    2016-12-01

    Full Text Available Valentina Perrone,1 Stefania Saragoni,1 Stefano Buda,1 Alessandro Broccoli,2 Luca Degli Esposti1 1CliCon S.r.l., Health, Economics & Outcomes Research, Ravenna, 2Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments in naïve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID. Patients were followed up for 4 weeks after ID (follow-up period and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb measurement after ID and the one prior to ID (ΔHb was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean ± standard deviation (SD age was 62.5±14.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8±11.8 years. The mean ± SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6±1.1 g/dL compared to those who started with a reference product (10.1±2.1 g/dL. No significant differences in ΔHb were

  8. Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians.

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    Koji Sugano

    Full Text Available Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians' perceptions of patients' decision-making incapacity.Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R. Cognitive impairment, depressive condition and other possible associated factors were also evaluated.Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32% were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen's kappa -0.54.Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity.

  9. Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis.

    Science.gov (United States)

    Lo, Sarah M; Choi, Murim; Liu, Jun; Jain, Dhanpat; Boot, Rolf G; Kallemeijn, Wouter W; Aerts, Johannes M F G; Pashankar, Farzana; Kupfer, Gary M; Mane, Shrikant; Lifton, Richard P; Mistry, Pramod K

    2012-05-17

    Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.

  10. Epidemiology of Monoclonal Gammopathy of Undetermined Significance (MGUS): The experience from the specialized registry of hematologic malignancies of Basse-Normandie (France).

    Science.gov (United States)

    Cabrera, Quentin; Macro, Margaret; Hebert, Benedikte; Cornet, Edouard; Collignon, Albert; Troussard, Xavier

    2014-08-01

    Multiple myeloma (MM) is the third most common haematologic malignancy in European countries, and is usually preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS). Therefore epidemiologic studies of MGUS are very limited in a population-based status. Here we report all new cases of MGUS exhaustively recorded by the Basse-Normandie Regional Registry for Hematologic Malignancies (a French region registry) between January 1997 and December 2005, and analyze outcome of patients until 2009 in term of evolution in MM or death. All cases were analyzed by an expert file review, and MGUS diagnosis was retained for: evidence of a monoclonal component <30 g/l and no CRAB criteria (hyperCalcemia, renal insufficiency, anemia, bone lesions). We showed that the world standardized incidence rate (WSR) for MGUS was 3.76 ± 0.26 per 100,000 inhabitants, increasing regularly with age, and that the median overall survival (OS) was 115.9 months (CI 95%: 10.5-130.2 months) with 78.3% patients alive at 5 years (CI 95%: 74.1-81.9%). We also observed a rate of progression to multiple myeloma of 1.41% per year, concordant with previous reports in a reallife exhaustive registry.

  11. Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-06-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  12. Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-01-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  13. Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center

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    M Sengar

    2015-01-01

    Full Text Available BACKGROUND: Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. AIMS: To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. SETTINGS AND DESIGN: This is a retrospective analysis from a tertiary care cancer center. MATERIALS AND METHODS: From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. RESULTS: A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%. CONCLUSIONS: The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms.

  14. 恶性血液病合并败血症的临床分析%Clinical analysis of malignant hematological disease combined with septicemia

    Institute of Scientific and Technical Information of China (English)

    叶海燕; 陈焯文; 吴奎海; 邓善威

    2014-01-01

    目的 研究恶性血液病合并败血症的临床特点、病原菌、药敏情况及防治措施.方法 回顾性分析2009年1月至2013年6月收治的95例恶性血液病合并败血症患者的临床资料.结果 95例患者一共发生110例次败血症,69.1%(76/110)为急性白血病患者,82.7%(91/110)患者中性粒细胞计数< 0.5×109/L,66.4%(73/110)患者粒细胞缺乏时间>7d,致病菌以革兰阴性菌为主,主要为大肠埃希菌(30.9%,34/110)、肺炎克雷伯杆菌(14.5%,16/110)、铜绿假单胞菌(12.7%,14/110).药敏以碳青霉烯类及阿米卡星最为敏感,经治疗110例次败血症中有98例次治愈或好转,95例患者中12例死亡,病死率12.6%(12/95),其中15例发生感染性休克的患者,7例死亡.结论 恶性血液病合并败血症病情重,进展迅速,容易发生感染性休克,病死率高,需对患者进行早期防治,并进行强有力的抗感染及积极支持治疗.%Objective To study the clinical characteristics,pathogens,drug sensitivity and prevention measures in malignant hematological disease combined with septicemia.Methods The clinical data of 95 malignant hematological disease combined with septicemia patients from January 2009 to June 2013 were retrospectively analyzed.Results One hundred and ten episodes of septicemia occurred in all the 95 patients,among which acute leukemia patients accounted for 69.1% (76/110),patients with neutrophil counts <0.5 × 109/L accounted for 82.7% (91/110),and patients with agranulocytosis time >7 days accounted for 66.4%(73/110).Major pathogenic bacteria was gram negative bacteria,including Escherichia coli 30.9%(34/110),Klebsiella pneumoniae (14.5%,16/110),Pseudomonas aeruginosa (12.7%,14/110).Carbapenems and amikacin was the most sensitive in susceptibility testing.Ninety-eight episodes of septicemia cured or improved,and 12 patients died,with a mortality of 12.6% (12/95).Fifteen patients had septic shock,of whom 7 patients

  15. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

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    Monica Fung

    Full Text Available Invasive fungal disease (IFD causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN. These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85 and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87 or overall mortality (RR 0.95, 95% CI 0.46-1.99. The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality

  16. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study.

    Science.gov (United States)

    Martinelli, Giovanni; Boissel, Nicolas; Chevallier, Patrice; Ottmann, Oliver; Gökbuget, Nicola; Topp, Max S; Fielding, Adele K; Rambaldi, Alessandro; Ritchie, Ellen K; Papayannidis, Cristina; Sterling, Lulu Ren; Benjamin, Jonathan; Stein, Anthony

    2017-06-01

    Purpose Few therapeutic options are available for patients with Philadelphia chromosome-positive (Ph(+)) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph(+) ALL. Patients and Methods This open-label phase II study enrolled adults with Ph(+) ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph(+) ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous

  17. Prevalence and predictors of solid or hematological malignancies in a monocentric cohort of HIV patients from central Italy

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    E Mazzotta

    2012-11-01

    Full Text Available Introduction: HIV-infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma (KS, non-Hodgkin's lymphoma (NHL, primary CNS lymphoma (PCL and invasive cervical cancers are considered AIDS-defining. An increased incidence in recent years, however, has been reported also for other malignancies after the introduction of HAART. Methods: We performed a case-control study to characterize all HIV-infected patients with both AIDS and non-AIDS-defining neoplasms observed among all consecutive patients followed at the Infectious Diseases Unit of Pescara General Hospital, since 1991 through 2012. All cases were matched with equinumerous controls without neoplasia homogeneous for age, sex and AIDS diagnosis. Results: Out of 626 patients consecutively assisted since 1991, 57 cases of malignancy (9.1% were observed. Of these, 45 (79.0% occurred in males; mean age was 43.6±9.3 years; 49 (86.0% patients were diagnosed with AIDS. Tumors observed were: NHL, 17 (29.8%; SK, 13 (22.8%; HCC, 5 (8.8%; CPL, 6 (10.5%; Hodgkin's lymphoma, 4 (7.0%; solid tumors, 12 (21.1%, including 1 AIDS-defining tumor (anal cancer. Among these, 37 (66.1% patients died; of them 14 (37.8% had non-AIDS cancers. Cases were well matched with the 55 controls for sex (p=0.9, age (p=0.6 and AIDS diagnosis (p=0.6. In comparison with controls, CD4 nadirs were not different (153±151 in controls vs 136±154 cells/mmc, while CD4 at tumor diagnosis were very different between controls (463±283 cells/mmc and cases (226±209 cells/mmc, p<0.0001. Among patients with malignancies, those who died had a non-significant reduction in CD4 counts (p=0.14; seemingly irrelevant were smoking status (p=0.9, working ability (p=0.4, HCV coinfection (p=0.4. Surprisingly, in patients co-infected with HBV, including HBsAg negative, antibody-positive subjects, tumors were significantly more frequent (60.7% vs. 38.8%, p=0.009. Conclusion: Factors potentially relevant for

  18. 恶性血液病的表观遗传学研究进展%Research progress of epigenetics in malignant hematological diseases

    Institute of Scientific and Technical Information of China (English)

    张玉凤; 叶芳

    2016-01-01

    表观遗传学是研究可遗传的、基因DNA序列不发生改变的基因表达调控的一门新学科.近年来,诸多研究结果均表明,表观遗传学异常改变在恶性血液病的发生、发展过程中起着十分重要的作用.相关基因异常甲基化是骨髓增生异常综合征(MDS)发生、发展的重要因素之一,并且与MDS患者的预后相关;微小RNA (miRNA)的异常甲基化与急性髓细胞白血病(AML)相关;zeste基因增强子同源物(EZH)2基因通过突变、缺失或过表达,甲基化下游靶基因调控其转录水平,从而与淋巴瘤等多种恶性血液病相关.针对表观遗传学异常改变的治疗方案给恶性血液病的免疫治疗赋予更广的内涵.笔者拟就表观遗传学异常改变在恶性血液病中的最薪研究进展,以及针对表观遗传学异常改变的免疫治疗方案的相关研究与应用前景进行综述.%Epigenetics is an emerging discipline studying the gene regulation and expression,which is heritable and not related to the changes in genetic DNA sequence.In recent years,a lot of evidences show that epigenetics plays an important role in the development of the malignant hematological diseases.Abnormal DNA methylation is one of the important factors in myelodysplastic syndrome (MDS) development,and related to its prognosis.Researches have proved that the microRNA (miRNA) methylation is associated with acute myeloid leukemia (AML).Enhancer of zeste homolog (EZH) 2 gene mutation,deletion,or overexpression is associated with lymphoma and other malignancies via regulating targeted gene expression level by methylation.Treatments aimed at epigenetic modification give immunotherapy of malignancies with wider implications.In this review,the latest research progress of epigenetics studies and the prospect of epigenetics therapy for malignant hematological diseases are summarized.

  19. Optimal Molecular Methods in Detecting p190BCR-ABL Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Rebecca J. Sonu

    2015-01-01

    Full Text Available Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI. Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR. A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS based assay and identified as the rare fusion variant e1a3 of p190BCR-ABL. Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results.

  20. Comparison of complications between transjugular and axillosubclavian approach for placement of tunneled, central venous catheters in patients with hematological malignancy: a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Hahn, Seong Tai [Catholic University of Korea, Diagnostic Radiology, Seoul (Korea)

    2005-06-01

    This study was designed to compare the incidence of mechanical, thrombotic and infective complications in transjugular (IJV) and axillosubclavian (SCV) central venous catheters (CVC) in patients with hematological malignancy. In a prospective observational trial, 131 consecutive patients were classified into two groups: Group A included those with IJV catheter insertions under sonography guidance (n=61) and group B included those with SCV insertions under venography guidance (n=70). After catheter placement, patients were prospectively acquired and recorded to obtain the following data: success rates, total catheter days, and complication episodes per 100 catheter days. All procedures were technically successful. Total catheter days were 7800 (group A) versus 8391(group B). Mechanical complications were observed in three cases from group A and 11 from group B, with an incidence rate of 0.04 per 100 catheter days versus 0.13 (P=0.043), respectively. Two symptomatic thrombotic complications were observed in group B. The number of infective complications was not significantly different between the two groups (P=0.312). There was no difference in infective complication incidence between the two groups. To minimize catheter-related mechanical and thrombotic complications, however, the IJV approach is superior to the SCV approach. (orig.)

  1. Etiology, clinical course and outcome of healthcare-associated bloodstream infections in patients with hematological malignancies: a retrospective study of 350 patients in a Finnish tertiary care hospital.

    Science.gov (United States)

    Åttman, Emilia; Aittoniemi, Janne; Sinisalo, Marjatta; Vuento, Risto; Lyytikäinen, Outi; Kärki, Tommi; Syrjänen, Jaana; Huttunen, Reetta

    2015-01-01

    This retrospectively collected laboratory-based surveillance data includes 575 healthcare-associated bloodstream infections (BSIs) in 350 patients with hematological malignancy in Tampere University Hospital, Finland, during 1999-2001 and 2005-2010. The most common underlying diseases were acute myelogenous leukemia (n=283, 49%), followed by myeloma (n=87, 15%) and acute lymphocytic leukemia (n=76, 13%). The overall rate was 9.1 BSIs per 1000 patient-days. Gram-positive BSIs predominated and the most common pathogens were coagulase-negative staphylococci (23%), viridans streptococci (11%), enterococci (9%) and Escherichia coli (9%). Fungi caused 2% of BSIs. The 7-day and 28-day case fatalities were 5% and 10% and were highest in BSIs caused by P. aeruginosa (19% and 34%, respectively). The median age of patients with BSI has increased; it was 55.0 years during 1999-2001, compared to 59.0 years in 2005-2007 and 59.0 years in 2008-2010 (p<0.0001). Gram-positive bacteria predominated in this material. Case fatalities were low as compared to previous reports although the median age of patients increased.

  2. High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders.

    Science.gov (United States)

    Caivano, Antonella; Laurenzana, Ilaria; De Luca, Luciana; La Rocca, Francesco; Simeon, Vittorio; Trino, Stefania; D'Auria, Fiorella; Traficante, Antonio; Maietti, Maddalena; Izzo, Tiziana; D'Arena, Giovanni; Mansueto, Giovanna; Pietrantuono, Giuseppe; Laurenti, Luca; Musto, Pellegrino; Del Vecchio, Luigi

    2015-12-01

    Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Waldenstrom's macroglobulinemia (WM), Hodgkin's lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls. EVs were isolated from serum of peripheral blood by ultracentrifuge steps and analyzed by flow cytometry to define count, size, and immunophenotype. MV levels were significantly elevated in WM, HL, MM, AML, and some MPNs and, though at a lesser degree, in CLL and NHL as compared to healthy controls. HL, MM, and MPNs generated a population of MVs characterized by lower size (below 0.3 μm) when compared to controls. MVs from patients specifically expressed tumor-related antigens, such as CD19 in B cell neoplasms, CD38 in MM, CD13 in myeloid tumors, and CD30 in HL. Both total and antigen-specific count of MVs significantly correlated with different HM clinical features such as Rai stage in CLL, International Prognostic Scoring System in WM, International Staging System in MM, and clinical stage in HL. MVs may represent a novel biomarker in HMs.

  3. Utility of the systemic inflammatory response syndrome (SIRS) criteria in predicting the onset of septic shock in hospitalized patients with hematologic malignancies.

    Science.gov (United States)

    Mato, Anthony; Fuchs, Barry D; Heitjan, Daniel F; Mick, Rosemarie; Halpern, Scott D; Shah, Payal D; Jacobs, Samamtha; Olson, Erin M; Schuster, Stephen J; Ujjani, Chaitra; Chong, Elise A; Loren, Alison W; Miltiades, Andrea N; Luger, Selina

    2009-06-01

    The systemic inflammatory response syndrome (SIRS) criteria have not been validated in patients with hematologic malignancies (HM). To determine whether daily assessment of SIRS criteria allows early identification of HM patients who will develop septic shock (SS). Observational, single-center,nested case-control study. Oncology unit of a tertiary care center. 547 consecutive, hospitalized, HM subject were enrolled. Using incidence-density sampling, 184 controls were matched to 46 SS cases. The study exposure was the SIRS score. The study outcome was the development of SS during the hospitalization. 8.4% of subjects developed SS. SIRS scores measured 24 hours prior to SS were significantly higher in cases than in controls (2.1 vs. 1.4,pSIRS cutpoints, fever, tachypnea and tachycardia were each associated with the onset of SS. Population-specific SIRS criteria were empirically derived. Single-center study. Further validation is warranted. SIRS can identify HM patients at risk for SS at least 24 hours before SS onset. These data may lead to evidence-based guidelines using routine vital signs to risk-stratify HM patients for SS.

  4. Application of decitabine in the treatment of hematological malignancies%地西他滨在恶性血液肿瘤治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    周冰

    2013-01-01

    地西他滨(DAC)是一种甲基化抑制剂,其不同于传统的化疗药物,具有独特的作用机制,并代表了新的治疗观念.甲基化存在于几乎所有的细胞内,通过抑制DNA甲基转移酶,引起DNA低甲基化和细胞分化或凋亡来发挥抗肿瘤作用.现就甲基化抑制剂DAC在恶性血液肿瘤治疗方面的应用进行综述.%Decitabine is a methylation inhibitor,which is different from traditional chemotherapy drugs,with new and unique mechanism of action,and represent a new therapeutic concept.Methylation present in almost all cells,by inhibiting DNA methyltransferase,causing hypomethylation of DNA and cell differentiation or apoptosis to anti-tumor effect.In this paper,methylation inhibitor decitabine treatment of hematological malignancies in the application are reviewed.

  5. Discussing and managing hematologic germ line variants.

    Science.gov (United States)

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-11-24

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  6. 儿童血液病血小板无效输注的机制和治疗%The treatment and mechanism of platelet transfusion refractoriness in pediatric hematological disorders

    Institute of Scientific and Technical Information of China (English)

    洪丹; 郑德菲; 卢俊; 肖佩芳; 孙伊娜; 吕慧; 翟宗; 翟钦; 杜智卓

    2015-01-01

    Objective To explore the treatment and mechanism of platelet transfusion refractoriness in pediatric hema-tological disorders.Methods Retrospective analyses were performed from 4 children diagnosed with platelet transfusion refractoriness between 2013 and 2014 in Children's Hospital of Soochow University. Clinical manifestation, laboratory tests, and the effect of plasma exchange were evaluated on pediatric platelet refractoriness.Results Two males and two females with age ranged from 2 years to 11 years and 9 months met the criteria of platelet refractoriness. Three cases were diagnosed as AML-M5 (M5), and one case was diagnosed as severe aplastic anemia (SAA). Platelet refractoriness occurred in one case of M5 after induction chemotherapy, and two cases in the stage of hematopoietic stem cell transplantation (HSCT). The SAA patient showed platelet refractoriness on her admission. The screening for HLA antibodies with the method of Immune Luminex beads streaming technology (Luminex) revealed that HLA-I antibody reaction were positive in three patients. All four patients showed a good response to the treatment of plasma exchange.Conclusions HLA-I class antibodies are closely associated with platelet refracto-riness, the plasma exchange treatment is effective and safe for platelet refractoriness in children.%目的 探讨儿童血液肿瘤患者血小板无效输注的分子学机制及治疗.方法回顾性分析2013年至2014年收治的4例血小板无效输注患儿的临床特征及实验室检查资料,评估血浆置换对儿童血小板无效输注的疗效.结果 4例患儿中男2例、女2例,年龄2岁~11岁9个月,其中3例为急性单核细胞白血病(M5),1例为重型再生障碍性贫血(SAA).1例M5患儿首次化疗后、2例M5患儿造血干细胞移植后发生血小板无效输注,1例SAA患儿入院时即表现为血小板无效输注.免疫磁珠流式液相芯片技术(Luminex)检测,3例患儿HLA-I类抗体阳性,1例患者HLA-I类阴性.

  7. The advantage of using SNP array in clinical testing for hematological malignancies--a comparative study of three genetic testing methods.

    Science.gov (United States)

    Xu, Xinjie; Johnson, Eric B; Leverton, Lisa; Arthur, Ashley; Watson, Quinn; Chang, Faye L; Raca, Gordana; Laffin, Jennifer J

    2013-01-01

    Cytogenetic methods, including G-banded chromosome analysis and fluorescence in situ hybridization (FISH) analysis, serve as a critical part of routine clinical testing for hematological malignancies and provide important diagnostic and prognostic information; however, the limitations of cytogenetic methods, including the requirement for actively dividing cells and lower resolution of G-banded chromosome analysis as well as the inability of both G-banded chromosome analysis and FISH to detect copy number neutral loss of heterozygosity (CN-LOH), can result in a failure to detect genomic abnormalities with diagnostic and prognostic significance. Here, we compared the abnormality detection rate of clinically requested testing (i.e., G-banded chromosome analysis and FISH) with high-resolution oligo (i.e., array comparative genomic hybridization (aCGH)) and single-nucleotide polymorphism (SNP)/oligo hybrid (i.e., SNP-CGH) arrays in a series of patients, in an effort to assess the ability of newer technologies to overcome these limitations. This series found the detection rate for SNP-CGH to be 62.5% for myelodysplastic syndrome (MDS) cases and 72.7% for chronic lymphocytic leukemia (CLL) cases, which are significantly higher than the detection rates of aCGH (31.3% for MDS and 54.5% for CLL) and G-banding and/or FISH (43.8% for MDS and 54.5% for CLL). This demonstrates the advantages of combining SNP-CGH with conventional cytogenetics to provide comprehensive clinical information by detecting clonality, large balanced rearrangements, copy number aberrations, and CN-LOH.

  8. Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis.

    Science.gov (United States)

    Yamamoto, Wataru; Andou, Taiki; Itabashi, Megumi; Koyama, Satoshi; Ishii, Yoshimi; Numata, Ayumi; Motohashi, Kenji; Hagihara, Maki; Matsumoto, Kenji; Fujisawa, Shin

    2016-01-01

    Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.

  9. Anti-T-lymphocyte globulin-based non-myeloablative stem cell transplantation followed by HLA-identical donor lymphocyte infusion for hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    毛平; 王顺清; 王汉平; 李庆山; 许艳丽; 莫文健; 应逸; 朱志刚

    2003-01-01

    Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 106/kg followed by the escalated dosage in the range of (0.5-1.5)×108/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.

  10. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2017-02-27

    Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia

  11. Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a phase I study.

    Science.gov (United States)

    Slavin, Shimon; Ackerstein, Aliza; Or, Reuven; Shapira, Michael Y; Gesundheit, Benjamin; Askenasy, Nadir; Morecki, Shoshana

    2010-10-01

    The feasibility and safety of immunotherapy mediated by intentionally mismatched rIL-2 activated killer lymphocytes (IMAK) with no prior stem cell engraftment was investigated in patients with advanced chemotherapy-resistant hematological malignancies and metastatic solid tumors. Our goals were to maximize anti-cancer activity by using intentionally mismatched donor lymphocytes; amplify killing of target cancer cells by rIL-2 activation of killer cells in vitro and in vivo, and avoid the risk of graft-versus-host disease (GVHD) by anticipated rejection of alloreactive donor lymphocytes. Conditioning consisted of 5 days of fludarabine 25 mg/m(2) or a single dose of cyclophosphamide 1,000 mg/m(2), 2 subcutaneous injections of alpha interferon (IFN) 3 x 10(6) and COX2 inhibitors, followed by administration of IMAK (65 +/- 5 CD3(+)CD56(-); 17 +/- 5 CD3(-)CD56(+)) in conjunction with low dose subcutaneous rIL-2 (6 x 10(6) IU/m(2)/day) for 5 days for continuous activation of alloreactive donor lymphocytes prior to their anticipated rejection. Here, we present our phase 1 clinical study data in a cohort of 40 high-risk patients with metastatic solid tumors and hematological malignancies. Treatment was accompanied by some malaise and occasional self-limited fever but otherwise well tolerated on an outpatient basis. Transient engraftment of donor cells was documented in two patients and only one developed self-limited grade 1 GVHD. Among patients with chemotherapy-resistant disease, long-term progression-free survival was recorded in 5 of 21 evaluable patients with metastatic solid tumors and in four of five patients with hematological malignancies. We conclude that the proposed procedure is feasible, safe, and potentially effective, with some otherwise resistant cancer patients long-term disease-free, thus justifying larger Phase II studies in patients with hematological malignancies and metastatic solid tumors, preferably at a stage of minimal residual disease with the

  12. AMG 319 Lymphoid Malignancy FIH

    Science.gov (United States)

    2016-01-20

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  13. 恶性血液病患者的医院感染特点及易患因素分析%Characteristic and vulnerable factors of nosocomial infection in patients with malignant hematologic disease

    Institute of Scientific and Technical Information of China (English)

    傅丽娟; 殷素珍; 王萍

    2001-01-01

    Objective To explore the characteristic and vulnerable factors of nosocomial infection in patients with malignant hematologic disease. Methods The clinical data of 208 patients with malignant hematologic disease were studied retrospectively. Results Nosocomial infection occurred in 102 patients, with 17 cases of multiple sites infection. 18 patients died of infection. Infection often located on oral mucosa and respiratory tract mucosa. Gram negative bacteria and fungi were the common pathogens. Chemotherapy, leucocytopenia , usage of broad - specrtum antibiotic, long hospitalization were the vulnerable factors of nosocomial infection. Con clusion Patients with malignant hematologic disease should be monitored closely, and those with leucocytes less than 2 × 109 be isolated protectively. Rational application of antibiotics should be emphasized.%了解恶性血液病患者发生医院感染的特点和易患因素。方法对208例恶性血液病患者医院感染情况,进行回顾性 分析。结果 208例病人发生102例感染。多部位感染17例。感染导致死亡18例。感染部位以呼吸道口腔粘膜最多见。感染病原菌主要 为G-菌和真菌。大剂量化疗、白细胞减少、广谱抗菌素使用、住院时间延长,是医院感染的易患因素。结论恶性血液病患者,应加强监 护。白细胞<2.0×109/L者,注意保护性隔离。应强调合理使用抗生素。

  14. Risk factors for infectious endocarditis in 2 patients with neutropenic hematological malignancy%两例粒细胞缺乏患者并发感染性心内膜炎危险因素分析

    Institute of Scientific and Technical Information of China (English)

    杨敏; 黄凌云; 王旭东; 王静波

    2012-01-01

    目的 了解血液病粒细胞缺乏患者并发感染性心内膜炎的临床特点.方法 回顾性分析2010年4、5月两例血液病粒细胞缺乏患者发生感染性心内膜炎过程、危险因素等.结果 两例患者在治疗肺部感染过程中,因病情需要均留置深静脉置管,并且在肺部感染好转时出现高热,并发感染性心内膜炎,赘生物均在左心系统.结论 血液病粒细胞缺乏患者容易发生感染性心内膜炎,可在数天内发生,留置深静脉导管可能是其发生的危险因素,一旦发生预后差,死亡率高,.%OBJECTIVE To investigate the clinical characteristics of infectious endocarditis in the patients with neutropenic hematological malignancy. METHODS Retrospective analysis of the development and risk factors for infectious endocarditis in 2 patients with neutropenic neutropenic hematological malignancy in Apr and May 2010 was performed. RESULTS During the therapy of pneumonia, both of the patients underwent indwelling deep venous catheter and had high fever again although the improvement of pneumonia, complicating with the infectious endocarditis. Echocardiogram demonstrated the excrescence in the left heart. CONCLUSION The patients with neutropenic neutropenic hematological malignancy are prone to the infectious endocarditis within several days, the indwelling deep venous catheterization may be the risk factor, the mortality is high and the prognosis is poor once it occurs.

  15. [From JSLH (The Japanese Society for Laboratory Hematology): An Active Team Approach to Medicine as Laboratory Technologists, through Showing Bone Marrow and Peripheral Blood Samples Directly to Patients with Hematological Malignancy].

    Science.gov (United States)

    Shimizu, Sanae; Kojima, Yukari; Saito, Kyoko; Wada, Hisako; Yamamoto, Masahiro; Morinaga, Koji; Kawai, Yasukazu; Haba, Toshihiro

    2014-11-01

    The clinical path for the treatment of acute myeloid leukemia (AML) patients has been in practice in our hospital since 2003. In the clinical path, laboratory technologists take on the role of explaining the microscopic findings in bone marrow and peripheral blood samples to patients (with or without their families) using the view-sharing microscope in our laboratory. From July 2003 to October 2014, 56 patients were enrolled in the AML clinical path and given an explanation of their bone marrow and peripheral blood samples. The patients' median age was 62, and the median time spent for explanation was 40 minutes. We conducted a questionnaire feedback survey involving those who enrolled, and the results showed significant improvement in the recognition of the disease pathophysiology, treatment efficacy, and the importance of precautions against infectious diseases. Based on the feedback, we have made marked efforts to provide patients with an improved environment during the explanatory session. This includes installing a special display for the patients, drawing a schematic illustration that shows how the blood cells differentiate, and putting them into operation in a hematology ward to promote patient privacy and precautions against infectious diseases. Hematological laboratory technologists have played an important role in patient care in our hospital. To perform their role as effectively as possible, hematological laboratory technologists participate in the conferences of the Department of Hematology and Oncology regularly, in which medical staff members can discuss the conditions and clinical courses of patients. We aim to contribute to patient satisfaction by sophisticating specialized knowledge as hematological laboratory technologists and cooperate with other medical staff members.

  16. Decreased complement mediated binding of antibody//sup 3/-dsDNA immune complexes to the red blood cells of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, R.P.; Horgan, C.; Buschbacher, R.; Brunner, C.M.; Hess, C.E.; O' Brien, W.M.; Wanebo, H.J.

    1983-06-01

    The complement mediated binding of prepared antibody//sup 3/H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.

  17. Assessment of Quality of Life of Patients with Hematologic Malignancies During Chemotherapy%恶性血液病患者化疗期间生活质量评价

    Institute of Scientific and Technical Information of China (English)

    罗科玲

    2012-01-01

    [目的]评价恶性血液病患者化疗期间的生活质量.[方法]所有患者根据其治疗的情况分为初治患者组、巩固化疗患者组、复发难治患者组,采用欧洲癌症研究与治疗组织(EORTC)QLQ-C30 3.0生活质量中文版对107例恶性血液病患者化疗期间进行生活质量评价.[结果]化疗期间,67例患者总体健康状况和社会功能受损严重,评分等级处于差25.2%(27/107)和非常差37.4%(40/107)的等级.相反认知功能、角色功能、情绪状态、躯体功能大部分处于良好状态,其中认知功能最好,89.7%(96/107)的患者认知处于好和非常好的状态,67.1%(72/107)、77.6%(83/107)、73.9%(79/107)患者的角色功能、情绪状态、躯体功能处于好和非常好的等级.在各项躯体症状领域中,64.48%(69/107)、80.37%(86/107)、57.94%(62/107)、67.29%(72/107)患者有中重度的便秘、恶心呕吐、缺乏食欲、疲乏等症状.三组患者在认知功能、社会功能评分差异无显著性,在总体健康状况、躯体功能、角色功能、情绪状态评分上,有显著性差异(P<0.05).在躯体症状评分,疲乏、疼痛、呼吸困难、失眠、腹泻等方面存在显著差异,其他症状无显著性差异.[结论]化疗期间患者总体健康状况和生活质量受到严重影响,须引起家庭、社会的重视和关注.%[Objective]To evaluate the quality of life of patients with hematologic malignancies during chemotherapy. [Methods]Questionnaires QLQ-C30 3. 0(Chinese version) of Kuropean organnization for research and treatment of cancer (KORTC) was used to assess the quality of life of 107 patients with hematologic malignancies during chemotherapy. [Re-sults]Global health status and social function in 25. 2%(27/107) and 37. 4%(40/107) of patients during chemotherapy were impaired gravely and at poor or very poor score grade, but most of cognitive function, role function, emotional state and somatic function were in good condition, and

  18. Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    Science.gov (United States)

    2015-12-14

    Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  19. Neonatal hematology.

    Science.gov (United States)

    Diaz-Miron, Jose; Miller, Jacob; Vogel, Adam M

    2013-11-01

    Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions. © 2013 Published by Elsevier Inc.

  20. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma

    Science.gov (United States)

    Yang, Wen-Chi; Lin, Sheng-Fung

    2015-01-01

    Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM. PMID:26649299

  1. Determinaton of Depression, Anxiety and Hopelessness Situations at Parents whose Children Are Followed in Gulhane Military Medical Faculty, Pediatric Hematology and Oncology Clinics Due to Any Malignancy or Chronic Disease

    Directory of Open Access Journals (Sweden)

    Mustafa Kamil Tuna

    2012-10-01

    Full Text Available Introduction: Chronic systemic diseases in childhood have negatively affecting the quality of life and debilitating effects for both children and parents. In our study, we investigated depression, anxiety and hopelessness situations at parents of children with these diseases. Materials and methods: The study was done at parents of children diagnosed with malignancy or chronic disease in GATA Department of Pediatrics Heath and Disease, Pediatric Hematology and Oncology Clinics. Beck Depression Scale, Beck Anxiety Scale and Beck Hopelessness Scale were applied to the participants. Results: Parents of children, who are followed due to malignancy or chronic disease in department of pediatrics heath and disease, pediatric hematology and oncology clinics, constituted the study group. 60 mothers and 51 fathers as study group and 64 mothers and 45 fathers as control group were enrolled in the study between 1st July 2009 and 1st June 2010. The mean age of the parents in study group was 35,7±5,1 and 33,3 5,6 age in control group. The depression score was significantly higher statistically in study group (p=0,035. No difference was fond for the anxiety and hopelessness scores between the groups (p=0,064 and p=0,695 respectively. There was no difference for depression, hopelessness and anxiety scores between mothers and fathers of the children (p=0,217, p=0,447, p=0,102, respectively. Conclusion: Without gender discrimination the parents of children with malignancy and chronic disease are in the risk group for depression. It is necessary to support the parents both socially and psychologically. [TAF Prev Med Bull 2012; 11(5.000: 577-582

  2. 恶性血液病患者化疗后并发败血症的临床分析%Clinical analysis of septicemia in hematologic malignancies patients after chemotherapy in

    Institute of Scientific and Technical Information of China (English)

    常晓丽; 董征; 孙琪云; 乔建辉; 余长林; 胡锴勋; 艾辉胜; 郭梅

    2013-01-01

    OBJECTIVE To investigate the susceptible factors,bacterial distribution,infection site,prognosis and treatment of septicemia in the hematologic malignancies patients after chemotherapy so as to guide the rational use of antibiotics.METHODS A total of 80 cases of hematologic malignancies patients complicated with septicemia,who underwent the chemotherapy from Jan 2008 to Dec 2011,were enrolled in the study,then the clinical data and the result of drug susceptibility testing were retrospectively analyzed.RESULTS Of totally 80 cases of hematologic malignancies patients complicated with septicemia,85.0% (68 cases) happened during the period of granulocytopenia.The Escherichia coli,Pseudomonas aeruginosa,and Klebsiella pneumoniae were the top three species of pathogens,accounting for 32.5%,20.0%,and 8.8%,respectively.Meropenem and linezolid were the most sensitive antibiotics against the gram-negative bacteria and the gram-positive bacteria.81.6% of the pathogenic bacteria causing the septicemia could be covered by empirical use of carbapenems antibiotics.CONCLUSION The gram-negative bacteria are the predominant pathogens in the hematologic malignancies patients complicated with septicemia after chemotherapy.The de-escalation therapy dominated by the carbapenems antibiotics can improve the cure rate of sepsis.The agranulocytosis,complication of pulmonary infection,septic shock,hematologic disease,empirical medication,and accordance to the drug susceptibility were the factors that could influence the prognosis.%目的 研究恶性血液病患者化疗后并发败血症的易感因素、病原菌分布、感染部位、预后及治疗,为临床合理使用抗菌药物提供参考依据.方法 回顾性分析2008年1月-2011年12月80例恶性血液病患者化疗后并发败血症的临床资料及药敏试验结果.结果 80例恶性血液病并发败血症患者中有68例处于化疗后粒细胞缺乏期占85.0%,;大肠埃希菌、铜绿假单胞

  3. Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.

    Science.gov (United States)

    Nieto, Yago; Shpall, Elizabeth J; Bearman, Scott I; McSweeney, Peter A; Cagnoni, Pablo J; Matthes, Steve; Gustafson, Dan; Long, Michael; Barón, Anna E; Jones, Roy B

    2005-04-01

    The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5). Five patients died from direct regimen-related organ toxicity (2 capillary leak syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m 2 , combined with melphalan (150 mg/m2 ) and carboplatin (1000 mg/m2 ). The MTD cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic enterocolitis. The remaining 25 patients presented the following extramedullary toxicity profile, which was manageable and largely reversible: stomatitis, myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities, and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m2 ). Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis. The response rate among 38 patients with measurable disease was 95%, with 47% complete responses. At a median follow-up of 26 months (range, 7-72 months), the 3-year event-free survival and overall survival were 26% and 36%, respectively. In conclusion, a 4-fold dose escalation of docetaxel, combined with melphalan and

  4. DCB - Cancer Immunology, Hematology, and Etiology Research

    Science.gov (United States)

    Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

  5. Palonosetron versus other 5-HT₃ receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States.

    Science.gov (United States)

    Craver, Chris; Gayle, Julie; Balu, Sanjeev; Buchner, Deborah

    2011-01-01

    This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting. Patients aged ≥ 18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed. Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p = 0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p = 0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p = 0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p = 0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain

  6. Analysis of clinical value of decitabine in the treatment of hematological malignancies%地西他滨用于治疗恶性血液肿瘤的临床价值分析

    Institute of Scientific and Technical Information of China (English)

    姚铠涛; 陈江声; 陈春莉

    2015-01-01

    Objective To analyze clinical value of decitabine in the treatment of hematological malignancies.Methods A total of 110 hematological malignancies patients as study subjects were randomly divided into observation group and control group, with 55 cases in each group. The observation group received decitabine for treatment, and the control group received gemcitabine. Clinical effects and adverse reactions of the two groups were observed.Results The observation group had much better total effective rate as 45.5% than 21.8% of the control group, and its incidence of adverse reactions was obviously lower as 45.5% than 70.9% of the control group. Their differences had statistical significance (P<0.05).Conclusion Decitabine provides precise effect in treating hematological malignancies, along with low incidence of adverse reactions. It contains positive value for clinical promotion.%目的 分析地西他滨用于治疗恶性血液肿瘤的临床价值.方法 110例恶性血液肿瘤患者作为研究对象, 随机分为观察组和对照组, 每组55例.其中观察组患者采用地西他滨治疗, 对照组患者采用吉西他滨治疗, 观察两组的临床疗效和不良反应.结果 观察组治疗总有效率45.5%明显优于对照组21.8%;观察组不良反应发生率45.5%明显低于对照组70.9%, 差异具有统计学意义(P<0.05).结论 地西他滨治疗恶性血液肿瘤疾病具有显著疗效, 不良反应发生率低, 具有积极的临床推广价值.

  7. Risk factors for oral infections in hematological malignancies patients after chemotherapy%血液恶性肿瘤患者化疗后口腔感染的危险因素分析

    Institute of Scientific and Technical Information of China (English)

    王亦素; 林海玉; 林晓骥; 王务萍

    2015-01-01

    OBJECTIVE To explore the risk factors for oral infections in hematological malignancies patients after chemotherapy and put forward the prevention countermeasures so as to provide guidance for clinical prevention of oral infections.METHODS A total of 224 patients with hematological malignancies who received the chemotherapy from Feb 2011 to Oct 2013 were recruited as the study objects,the prospective study was conducted;the univari-ate chi-square test and non-conditional multivariate logistic regression analysis were performed for the risk factors for the oral infections after the chemotherapy.RESULTS The oral infections occurred in 42 of 224 patients under-going the chemotherapy with the infection rate of 18.8%,among whom the patients with buccal infections accoun-ted for 38.1%,the patients with gingival infections 23.8%.The multivariate logistic regression analysis indicated that the age,level of serum albumin less than 40 g/L,absolute value of granulocytes less than 0.5×109/L,poor oral environment,bad oral self-cleaning habits,multiple cycles of chemotherapy,and no alleviation after chemo-therapy were the high risk factors for the oral infections in the hematological malignancies patients after the chemo-therapy.CONCLUSION There are a variety of risk factors for the oral infections in the hematological malignancies patients after the chemotherapy.It is necessary to strengthen the infection control measures and take active inter-ventions to the risk factors so as to reduce the incidence of oral infections.%目的:探讨血液恶性肿瘤患者化疗后并发口腔感染的危险因素及防治对策,为临床预防口腔感染提供参考。方法选取2011年2月-2013年10月收治的224例血液恶性肿瘤接受化疗患者为研究对象,给予前瞻性研究,对化疗后发生口腔感染的可能危险因素进行单因素χ2检验以及多因素非条件logistic 回归分析。结果224例化疗患者中有42例发生口腔感染,感染率18

  8. Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study.

    Science.gov (United States)

    Contejean, Adrien; Lemiale, Virginie; Resche-Rigon, Matthieu; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Darmon, Michael; Jourdain, Mercé; Renault, Anne; Schlemmer, Benoît; Azoulay, Elie

    2016-12-01

    Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p 7 (OR 3.32 (95% CI 2.15-5.15); p undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.

  9. 普通血液病房恶性血液病患者念珠菌定植及侵袭性真菌感染的观察%Candida colonization and invasive fungal infection in hospitalized patients with hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    赖悦云; 鲍立; 卢锡京; 路瑾; 余进; 李若瑜; 黄晓军

    2009-01-01

    Objective To investigate thee status of Candida colonization and the risk factors of invasive fungal infection (IFI) in hospitalized patients with hematological malignancies. Methods 114 patients with hematological malignancies admitted to the hematology wards from May 2004 to April 2005 underwent fungal culture of their samples of urine, feces, and saliva once a week until the end of the sixth week of hospitalization or they were discharged. Culture of blood, sputum, or sterile body fluids were carried out when the patients were suspected to have IFI. Results 165 strains of Candida spp. were isolated from 46 of the 114 patients, C. albicans accounting for 78. 8% and non-albicans Candida for 21.2% respectively. Candida was found in 38 patients (35. 3% ) were found to have colonization of Candida, chiefly C. albicans (76. 3% ). The risk factors of Candida colonization included long duration of leucopenia (WBC 10 d是IFI的危险因素.

  10. Lenalidomide, as a single agent, induces complete remission in a refractory mantle cell lymphoma

    OpenAIRE

    Tempescul, Adrian; Ianotto, Jean-Christophe; Morel, Frederic; Morel, Frédéric; Marion, Veronique; De Braekeleer, Marc; Berthou, Christian

    2009-01-01

    Lenalidomide, as a single agent, induces complete remission in a refractory mantle cell lymphoma phone: +33-298-223504 (Tempescul, Adrian) (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan - Avenue Foch - 29609 - Brest - FRANCE (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan - Avenue Foch - 29609 - Brest - FRANCE (Ianotto, Jean-Christophe) ...

  11. 造血干细胞移植治疗恶性血液病的研究与分析%Hematopoietic stem cell transplantation for treating hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    吴必嘉; 龚峻梅; 郭天剑; 陈万红; 李娜

    2012-01-01

    BACKGROUND: In recent years, with the continuous development of hematology and related fields of basic and clinical research, hematopoietic stem cell transplantation has become an effective means of treatment for hematologicmalignancies, or even the only way to cure certain blood diseases.OBJECTIVE: According to the literature retrieval results, to comparatively analyze the literatures on the hematopoieticstem cell transplantation for treating hematological malignancies in SCI database and to explore the future developmenttendency of hematopoietic stem cell transplantation for treating hematological malignancies.METHODS: A retrieval was performed for the literature of the hematopoietic stem cell transplantation for treatinghematological malignancies, using key words of “hematopoietic stem cell, transplantation, acute myelogenous leukemia,non-hodgkin lymphoma, chronic myelocytic leukemia” between 2001-01 and 2010-12 in SCI database. The retrievalresults were analyzed, and the trends were described in words and graphics.RESULTS AND CONCLUSION: The overall literatures of the hematopoietic stem cell transplantation for treatinghematological malignancies had an upward trend from 2001 to 2010. United States published more literature than othercountries, which play an important role in the field of the hematopoietic stem cell transplantation for treatinghematological malignancies. Most of literatures were published from Fred Hutchinson Cancer Research Center. Thispaper provides a valuable reference for researchers to understand the overview and present situation of this field.%背景:近年来,随着血液学及相关领域基础和临床研究的不断发展,造血干细胞移植已成为治疗恶性血液病的有效手段,甚至是治愈某些血液病的惟一方法.目的:对造血干细胞移植治疗恶性血液病SCI数据库文献资料进行多层次对比分析.方法:通过计算机检索SCI数据库2001/2010有关造血干细胞移植治疗恶性血液

  12. Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Hematologic Malignancies Undergoing Donor Peripheral Blood Stem Cell Transplant

    Science.gov (United States)

    2016-09-06

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B -Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  13. Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2016-10-26

    Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Severe Combined Immunodeficiency; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

  14. Avian hematology.

    Science.gov (United States)

    Jones, Michael P

    2015-01-01

    Avian veterinarians often rely heavily on the results of various diagnostic tests, including hematology results. As such, cellular identification and evaluation of the cellular response are invaluable tools that help veterinarians understand the health or condition of their patient, as well as to monitor severity and clinical progression of disease and response to treatment. Therefore, it is important to thoroughly understand how to identify and evaluate changes in the avian erythron and leukon, as well as to interpret normal and abnormal results.

  15. Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

    Science.gov (United States)

    2016-01-05

    Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood

  16. CLINICAL ANALYSIS OF CASPOFUNGIN IN TREATMENT OF HEMATOLOGICAL MALIGNANCIES COMBINED INVASIVE PULMONARY ASPERGILLOSIS INFECTION%卡泊芬净治疗恶性血液病合并IPA感染临床分析

    Institute of Scientific and Technical Information of China (English)

    梁莉; 申徐良; 张梅香; 张国香; 魏武

    2014-01-01

    目的:评估卡泊芬净治疗恶性血液病合并侵袭性肺曲霉菌(IPA)感染的临床疗效和安全性。方法:2008年1月-2012年12月恶性血液病合并IPA感染患者49例,所有患者均经CT检查和GM试验临床诊断;采用注射用醋酸卡泊芬净进行治疗,根据临床疗效标准,评价卡泊芬净治疗的疗效和安全性。结果:49例患者的治疗总有效率为91.84%(45/49)。卡泊芬净治疗过程中9例发生不良反应,不良反应发生率为18.37%。结论:卡泊芬净有很好的抗真菌活性,是治疗恶性血液病合并肺曲霉菌感染安全有效的药物。%Objective:To evaluate the clinical efficacy and safety of caspofungin in treatment of hematological malignanciescombinedinvasivepulmonaryaspergillosis(IPA)infection.Methods:49hematologicalmalignanciescombined IPA infection patients (2008.1-2012.12) that were diagnosed by CT and galactomannan test were treated with caspofungin. The clinical efficacy and safety of caspofungin were evaluated according to clinical curative effect standard.Results:The total effective rate of 49 patients was 91.84%(45/49) after caspofungin treatment;and the incidence of drug related adverse events was 18.37%(9/49).Conclusions:Caspofungin has good antifungal activity, and it is a safe and effective drug for treating hematological malignancies combinedIPAinfection.

  17. The European Hematology Association Roadmap for European Hematology Research

    DEFF Research Database (Denmark)

    Engert, Andreas; Balduini, Carlo; Brand, Anneke

    2016-01-01

    research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness...... diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs...... across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments...

  18. Efficacy of voriconazole in treatment of invasive fungal infections in elderly patients with hematological malignancies%伏立康唑治疗老年恶性血液病侵袭性真菌感染疗效分析

    Institute of Scientific and Technical Information of China (English)

    陆敏秋; 白砚霞; 李真; 左杏果; 吴梦青; 石磊; 褚彬

    2012-01-01

    OBJECTIVE To clarify the efficacy of voriconazole for the invasive fungal infections (IFI) in the elderly patients with hematological malignancies and observe the adverse reactions. METHODS The clinical data of 50 elderly IFI patients with hematological malignancies who were treated with voriconazole from May 2007 to Dec 2011 were analyzed retrospectively. RESULTS There were 4 cases confirmed, 20 cases clinically diagnosed, and 26 cases suspected; there were 14 cases treated with initial therapy, 36 cases with rescue therapy; the total effective rate was 74. 0%, 4 confirmed cases were proven effective to voriconazok, the effective rate of the clinically . diagnosed cases was 70. 0 %, the suspected diagnosis group 73. 1 %; the effective rate of the initial therapy was 85. 7 % , the rescue therapy 89. 4 % ; the effective rate of the patients receiving intravenous injection was 76. 3 %, the patients treated with simple oral administration 66. 7% , the differences were not statistically significant; there were totally 10 patients infected with Aspergillus, 5 cases were effective and Aspergillus were eradicated. Agranulocytosis affected the efficacy of voriconazole, the response rate of agranulocytosis group was 58. 4% , lower than 88. 5% of the non-agranulocytosis group (P<0. 05) ; the abnormal liver function, visual impairment,and hallucination were the main adverse reactions, which disappeared as drugs were withdrawn, the renal toxicity and cardiac toxicity were not observed. CONCLUSION Voriconazole is effective and safe, as is applied for the treatment of invasive fungal infections in elderly patients with hematologic malignancies.%目的 探讨伏立康唑在老年恶性血液病侵袭性真菌感染患者中的临床疗效及不良反应.方法 对2007年5月-2011年12月的50例老年恶性血液病侵袭性真菌感染患者的临床资料进行回顾性分析.结果 确诊4例,临床诊断20例,拟诊26例;14例患者为初始治疗,36例患者为挽

  19. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Mahmoud Aljurf

    2016-01-01

    Full Text Available Background. We studied DNA chimerism in cell-free DNA (cfDNA in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126 showed that, of 84 patients with 100% donor DNA in PMN, 16 (19% had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19% showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41% showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

  20. The role of ¹⁸F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia.

    Science.gov (United States)

    Gafter-Gvili, Anat; Paul, Mical; Bernstine, Hanna; Vidal, Liat; Ram, Ron; Raanani, Pia; Yeshurun, Moshe; Tadmor, Boaz; Leibovici, Leonard; Shpilberg, Ofer; Groshar, David

    2013-09-01

    We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia.

  1. 获得性21三体恶性血液病的临床和细胞遗传学特征%Clinical and cytogenetic features of hematologic malignancies associated with acquired trisomy 21

    Institute of Scientific and Technical Information of China (English)

    王焕萍; 倪万茂; 陈志妹; 楼基余; 徐欢; 俞运彪; 钱文斌; 金洁

    2008-01-01

    目的 分析21三体恶性血液病患者的临床及细胞遗传学特点.方法 采用骨髓直接法和(或)培养法制备染色体标本,采用R显带技术进行核型分析,并进行临床随访.结果 共发现25例患者存在21三体,其中急性髓系白血病(acute myeloid leukemia,AML)13例,占同期进行染色体检查的AML患者总数的1.5%,包括M5h6例;急性淋巴细胞(acute lymphoblastic leukemia,ALL)8例,占同期进行染色体检查的ALL患者总数的2.2%,其它类型4例.25例中13例为单纯获得性21三体,其余病例均合并其它异常.随访的19例患者的中位生存期为9个月.结论 单纯21三体在AML中以M5b多见,伴21三体异常的恶性血液病预后还存在争议.%Objective To investigate the association between trisomy 21 abnormalities and the clinical and cytogenetie features of hematologic malignancies. Methods Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding. Results Thirteen patients (1.5 % ) with acute myeloid leukemia (AML) including 6 cases of M5b,8 (2.2 % ) with acute lymphoblastie leukemia (ALL) and4 cases with other hematologic malignancies had aquired trisomy 21, and in 13 patients it oceurred as the sole eytogenetic abnormality. The remaining had combination with other abnormalities. The median survival for the 19 patients with trisomy 21 was 9 months. Conclusion M5b was the major type in AML with sole acquired trisomy 21. Trisomy 21 as the sole abnormality appeared to have a poor prognosis.

  2. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies.

    Science.gov (United States)

    Valsasina, Barbara; Beria, Italo; Alli, Cristina; Alzani, Rachele; Avanzi, Nilla; Ballinari, Dario; Cappella, Paolo; Caruso, Michele; Casolaro, Alessia; Ciavolella, Antonella; Cucchi, Ulisse; De Ponti, Anna; Felder, Eduard; Fiorentini, Francesco; Galvani, Arturo; Gianellini, Laura M; Giorgini, Maria L; Isacchi, Antonella; Lansen, Jaqueline; Pesenti, Enrico; Rizzi, Simona; Rocchetti, Maurizio; Sola, Francesco; Moll, Jürgen

    2012-04-01

    Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings.

  3. Refractory duodenal ulcer

    Directory of Open Access Journals (Sweden)

    Al Freihi Hussein

    1995-01-01

    Full Text Available Refractory or intractable ulcer is defined as an ulcer that fails to heal completely after eight to twelve weeks, despite appropriate treatment with a modern antiulcer therapy in a compliant patient. Refractory ulcer should be suspected in individuals diagnosed to have peptic ulcer if their symptoms persist longer than usual: occurrence of complications or simply their ulcers fail to heal, since up to 25% of such patients remain asymptomatic. Conditions associated with refractory ulcer include noncompliance, continuous consumption of nonsteroidal anti-inflam-matory drugs, acid hypersecretion, smoking. male gender and other factors with questionable role like advanced age, large ulcer size, prolonged duration of symptoms and the presence of complication like bleeding. Nonpeptic ulcers like tuberculosis, malignancy, Crohn′s disease and primary intestinal lymphoma should always be considered in the differential diagnosis. Colonization with H. pylori which is well-known as a cause of frequent recurrences, has not been linked with refractoriness. Patients with refractory ulcers must undergo thorough re-evaluation including repeated endoscopies, obtaining biopsies for microbiology and histology and determination of serum-gastrin level. Once diseases with identifiable etiologies have been ruled out, aggressive medical management with single or multiple antiulcer drugs should be instituted. Such treatments will virtually heal all refractory ulcers. Surgery should be reserved for patients whose ulcers fail to respond to optimal medical therapy or those who develop com-plications necessitating surgical intervention.

  4. Comparison of DNA Microarray, Loop-Mediated Isothermal Amplification (LAMP) and Real-Time PCR with DNA Sequencing for Identification of Fusarium spp. Obtained from Patients with Hematologic Malignancies.

    Science.gov (United States)

    de Souza, Marcela; Matsuzawa, Tetsuhiro; Sakai, Kanae; Muraosa, Yasunori; Lyra, Luzia; Busso-Lopes, Ariane Fidelis; Levin, Anna Sara Shafferman; Schreiber, Angélica Zaninelli; Mikami, Yuzuru; Gonoi, Tohoru; Kamei, Katsuhiko; Moretti, Maria Luiza; Trabasso, Plínio

    2017-03-21

    The performance of three molecular biology techniques, i.e., DNA microarray, loop-mediated isothermal amplification (LAMP), and real-time PCR were compared with DNA sequencing for properly identification of 20 isolates of Fusarium spp. obtained from blood stream as etiologic agent of invasive infections in patients with hematologic malignancies. DNA microarray, LAMP and real-time PCR identified 16 (80%) out of 20 samples as Fusarium solani species complex (FSSC) and four (20%) as Fusarium spp. The agreement among the techniques was 100%. LAMP exhibited 100% specificity, while DNA microarray, LAMP and real-time PCR showed 100% sensitivity. The three techniques had 100% agreement with DNA sequencing. Sixteen isolates were identified as FSSC by sequencing, being five Fusarium keratoplasticum, nine Fusarium petroliphilum and two Fusarium solani. On the other hand, sequencing identified four isolates as Fusarium non-solani species complex (FNSSC), being three isolates as Fusarium napiforme and one isolate as Fusarium oxysporum. Finally, LAMP proved to be faster and more accessible than DNA microarray and real-time PCR, since it does not require a thermocycler. Therefore, LAMP signalizes as emerging and promising methodology to be used in routine identification of Fusarium spp. among cases of invasive fungal infections.

  5. Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto.

    Science.gov (United States)

    Menichetti, F; Del Favero, A; Martino, P; Bucaneve, G; Micozzi, A; Girmenia, C; Barbabietola, G; Pagańo, L; Leoni, P; Specchia, G; Caiozzo, A; Raimondi, R; Mandelli, F

    1999-02-01

    To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections, a randomized, placebo-controlled, double-blind, multicenter trial was conducted: 405 neutropenic patients with hematologic malignancies were randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201 patients), or placebo (204 patients). Proven and suspected deep fungal infection occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole recipients and in 4% of placebo recipients, a difference of 3.5 percentage points (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the itraconazole recipients compared with 4 placebo recipients, a difference of 2 percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was documented in four itraconazole recipients (one death) and one placebo recipient (one death). Side effects causing drug interruption occurred in 18% of itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to Candida species.

  6. Loss of Thy-1 (CD90) antigen expression on mesenchymal stromal cells from hematologic malignancies is induced by in vitro angiogenic stimuli and is associated with peculiar functional and phenotypic characteristics.

    Science.gov (United States)

    Campioni, D; Lanza, F; Moretti, S; Ferrari, L; Cuneo, A

    2008-01-01

    Little is known about human mesenchymal stromal cell (hMSC) phenotypic and functional subsets in response to environmental stimuli. The strategy used in this study focused on defining hMSC functional subpopulations based in particular on their Thy-1 (CD90) antigen (Ag) surface expression. The effect of different in vitro microenvironmental conditions on the isolation and expansion of bone marrow-derived (BM) hMSC from hematologic malignancies (HM) and normal samples (NS) was assayed. hMSC clonogenic and differentiation potential, phenotypic profile and long-term capacity to sustain in vitro hemopoiesis were considered in relation to the different expansion protocols. The results showed that angiogenic supplements used in combination with low serum content gave rise to the appearance of Thy-1(-) HM-MSC with high proliferative potential, capable of restoring the typical HM stromal impairment. The expression of the CD271 was partially maintained. We further report an enhancement towards the osteogenic and adipogenic differentiation capacity by the Thy-1(-) HM-MSC subset. Despite the angiogenic treatment, the Thy-1(-) MSC stopped short of full endothelial differentiation. In this paper we provide evidence that in vitro angiogenic stimuli generate HM-MSC lacking CD90 Ag expression. The Thy-1(-) MSC subset is characterized by peculiar functional and phenotypic characteristics, thus supporting the role played by the microenvironment in selecting particular hMSC subsets maintaining normal tissue homeostasis or inducing pathologic processes.

  7. 老年恶性血液病患者化疗后急性心力衰竭的危险因素%Risk factors of acute heart failure in elderly patients with hematologic malignancies after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    李皓亮; 袁义燕

    2013-01-01

    Objective:Study of risk factors in elderly patients with malignant hematological diseases occur in acute heart failure after chemotherapy.Methods:From 2012 March to 2013 March in our hospital in patients with hematologic malignancies therapy in 230 cases, a retrospective analysis of 230 cases with sex , fluid balance weight , hemoglobin , septic shock and sepsis , total course of chemotherapy , renal failure, respiratory failure, neutropenia, and heart disease index.Results:gender, total course of chemotherapy, renal insufficiency and respiratory failure in the two groups, the difference was not statistically significant (P >0.05); agranulocytosis and heart disease between the two groups, significant differences were statistically significant (P <0.05); liquid balance weight,hemoglobin values and infection shock and sepsis in two groups , significant differences were statistically significant (P <0.001).Conclusion:the risk of aged malignant hematonosis patients with acute heart failure after chemotherapy in the complicated factors , early diagnosis , intervention therapy is crucial to the early .%目的:研究观察老年恶性血液病患者在化疗后发生急性心力衰竭的危险因素。方法:选取2012年3月~2013年3月期间在我院住院治疗的恶性血液病患者230例,回顾性分析本组230例患者的性别、液体平衡量、血红蛋白值、感染性休克/脓毒血症、化疗总疗程、肾功能不全、呼吸衰竭、粒细胞缺乏、以及心脏病史等指标。结果:性别、化疗总疗程、肾功能不全以及呼吸衰竭2组比较,差异均无统计学意义(P均>0.05);粒细胞缺乏以及心脏病史2组比较,差异显著均有统计学意义(P均<0.05);液体平衡量、血红蛋白值以及感染性休克/脓毒血症2组比较,差异显著均有统计学意义(P均<0.001)。结论:老年恶性血液病患者在化疗后发生急性心力衰竭的危险因素复杂多样,

  8. Matriz extracelular e enzimas degradatórias na hematopoese e doenças onco-hematológicas Extracellular matrix in hematopoiesis and hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Juliana L. Dreyfuss

    2008-10-01

    differentiation of these cells is attained through the interaction of the cells with the bone marrow microenvironment. The adhesion of hematopoietic progenitors to ECM molecules and the integrin activation are modulated by a variety of cytokines and growth factors, and this modulation seems to be the mechanism of regulation that influences proliferation of hematopoietic cells, transendothelial/transstromal migration and homing. Both in the migration and homing process, and in tumoral invasion the cells undergo the following steps: 1 - Degradation of the ECM by enzymes, including metalloproteinase, collagenase, plasmin, cathepsin, glycosidase and heparanase, secreted by the cells; 2 - Cell migration through the region previously degraded by enzymes; and 3 - Cell adhesion to specific receptors located on the cellular surface, that generally interact with ECM components. In onco-hematologic diseases, the interaction of neoplastic cells with the extracellular matrix also influences aggressiveness and prognosis of the disease.

  9. Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies: a single-institute analysis

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-hong; XU Lan-ping; LIU Dai-hong; CHEN Huan; ZHANG Xiao-hui; HAN Wei; WANG Feng-rong

    2013-01-01

    Background Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients.Our aim was to assess the leukemia-free survival (LFS) and some primary results,such as hematologic recovery,risk of graft-versus-host disease (GVHD),relapse,and long-term survival,after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n=38),bone marrow (UBMT n=28,transplanted before January 2003),or peripheral blood stem cells (UPBSCT n=46,transplanted after January 2003) between July 2000 and July 2008 were analyzed.Results Except that the patients were much younger in the UCBT group (median age,10.5 years in UCBT,30 years in UPBSCT,and 20 years in UBMT),other pre-transplant parameters,such as gender,diagnosis,and the phase of disease,were comparable.All patients received myeloablative regimens,primarily including BUCY; however,there was less antithymocyte globulin (ATG) used for the UBMT patients (2138 in UCBT,0/46 in UPBSCT,and 8/28 in UBMT did not use ATG,P=0.000).Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets.The cumulative allo-engraftment rates were also significantly lower (87.8% vs.97.8% vs.100% for WBC,P=0.000; 73.0% vs.97.5% vs.89.5% for PLT,P=0.000) for UCBT.The incidence of Grade 2-4 and 3-4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%,40.2% and 10.5%,and 77.4% and 41.2%,respectively,for UCBT,UPBSCT,and UBMT,P=0.000).The occurrence of extensive chronic GVHD (cGVHD)was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%,P=0

  10. 恶性血液病病人自我感受负担及影响因素调查分析%Survey and analysis of self perceived burden of patients with malignant hematologic diseases and its influencing fac-tors

    Institute of Scientific and Technical Information of China (English)

    景颖颖; 李燕; 张蕙

    2015-01-01

    Objective:To investigate and analyze the main influencing factors of self perceived burden of patients with malignant hematologic diseases.Methods:A total of 1 1 0 patients with malignant hematologic diseases re-ceived the questionnaire by using the general information questionnaire,daily life ability scale (ADL)and self perceived burden scale (SPBS).Results:The score of self perceived burden of patients with malignant hemato-logic diseases was (34.73±6.48),97.27% of patients had different levels of self perceived burden.The multiple stepwise regression analysis showed that marital status,family per capita monthly income,daily life ability were the influencing factors of patients with malignant hematologic diseases.Conclusion:Patients with malignant he-matologic diseases had obvious self perceived burden usually,the clinical nursing personnel should understand the influencing factors of patients’self perceived burden and give them the corresponding interventions,so as to lighten their self perceived burden and improve their physical and mental health and quality of life.%[目的]调查分析影响恶性血液病病人自我感受负担的主要因素。[方法]采用自行设计的一般资料调查表、日常生活能力量表(ADL)及自我感受负担量表(SPBS )对110例恶性血液病病人进行问卷调查。[结果]恶性血液病病人的自我感受负担得分为34.73分±6.48分,97.27%病人存在不同程度的自我感受负担。多元逐步回归分析结果显示,婚姻状况、家庭人均月收入、日常生活能力等是恶性血液病病人自我感受负担的影响因素。[结论]恶性血液病病人普遍存在明显的自我感受负担,临床护理人员应了解病人自我感受负担的影响因素并给予相应的干预措施,从而减轻恶性血液病病人的自我感受负担,提高其身心健康和生活质量。

  11. 血液病合并侵袭性肺部真菌感染的外科治疗%Surgical treatment of invasive pulmonary fungal infections in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    葛锦峰; 马晓; 郑世营; 蒋东; 马海涛

    2014-01-01

    目的 总结血液病合并侵袭性肺部真菌感染的外科治疗经验.方法 2000年1月至2012年12月,共收治血液病合并侵袭性肺部真菌感染的病患78例,其中男49例,女29例,平均29.6岁.所有患者术前全部接受过相应方案化疗,疗程1~3次不等,平均抗真菌治疗时间4周.58例患者选择常规开胸手术,其中实施肺段切除者2例,肺叶切除者39例,单纯病灶楔形切除者17例;20例患者选择微创胸腔镜手术,其中全腔镜或腔镜辅助下肺叶切除者15例,单纯病灶楔形切除者5例.结果 所有患者皆顺利完成手术,平均手术时间(125.3 ±35.7) min、术中失血(253.1±42.8)ml.术后无严重并发症,渗血超过1 000 ml者8例,持续漏气大于7天者6例.外科住院时间(7.8±2.5)天,无术后30天再手术及死亡病例.随访6~ 24个月,术后预防性抗真菌治疗者38例,无真菌扩散或复发者.结论 血液病并发肺部真菌感染的患者,在内科保守治疗无效时,选择积极的外科手术治疗是安全且有益的.%Objective To summarise the experience of surgical treatment of invasive pulmonary fungal infection in patients with hematologic malignancies.Methods From Jan.2000 to Dec.2012,78 hematologic patients with invasive pulmonary fungal infections,including 49 males and 29 females with average age of 29.6 years,underwent surgical treatment.Preoperatively,all patients with 1 to 3 courses of chemotherapy had received average 4 weeks antifungal treatment.There were 58 cases received conventional open thoracic surgery and 20 cases received VATS including lobectomy,segmentectomy,wedgectomy.Results The procedures were successful,the average operation time w as(125.3 ± 35.7) min and intraoperative blood loss was(253.1 ± 42.8) nl.There were no severe postoperative complications.The main complications were excessive effusion (10.2%) and persistence airleak (7.7%).The hospital days was(7.8 ± 2.5) days,no reoperation and death case in 30 days

  12. Dynamic contrast-enhanced MRI for the evaluation of bone marrow microcirculation in hematologic malignancies before and during thalidomide therapy; Dynamische kontrastverstaerkte MRT zur Beurteilung der Knochenmarksmikrozirkulation bei malignen haematologischen Erkrankungen vor und waehrend einer Thalidomidtherapie

    Energy Technology Data Exchange (ETDEWEB)

    Scherer, A.; Wittsack, H.J.; Engelbrecht, V.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Strupp, C.; Germing, U.; Gattermann, N.; Haas, R. [Duesseldorf Univ. (Germany). Klinik fuer Haematologie, Onkologie und klinische Immunologie; Willers, R. [Duesseldorf Univ. (Germany). Universitaetsrechenzentrum

    2002-03-01

    Purpose. The aim of the study was to measure microcirculation parameters by dynamic contrast-enhanced MRI (d-MRI) and to evaluate the anti-angiogentic effects during treatment with thalidomide in different hematologic malignancies. Methods. In 20 healthy normal persons, 20 patients with myelodysplastic syndromes (MDS), 10 patients with multiple myeloma (MM) and 10 with myelofibrosis (MF) a fast gradient echo sequence (Turbo fast low angle shot 2D) with a pump controlled bolus infusion of gadolinium-DTPA was performed before and in 18 of these after beginning (average of 4,3 months) of a thalidomide therapy. Two pharmacokinetic parameters - the amplitude and exchange-rate-constant - were calculated and a statistical comparison of these values between healthy persons and patients as well as a correlation with the clinical course was executed. Results. Compared with the normal controls the patients showed a higher amplitude (normal persons 14.4{+-}5.2, MDS 24.8{+-}8.1, MF 35.9{+-}4.3, MM 23.4{+-}3.6) and exchange-rate-constant (normal persons 0.124{+-}0.042, MDS 0.136{+-}0.036, MF 0.144{+-}0.068, MM 0.131{+-}0.034). In the d-MRI-follow-up examinations a signficant (p<0.005) reduction of the amplitude and exchange rate constant values was evident in 14 of 18 patients undergoing a thalidomide therapy. Clinically all of these patients showed a therapy responding with complete or partial diseases remission. Conclusions. In patients with hematologic malignancies significantly higher d-MRI-microcirculation parameters of the lumbar spine can be demonstrated than in normal persons. During anti-angiogenetic treatment with thalidomide a decrease of these values was observed in case of a responding to therapy. (orig.) [German] Fragestellung. Unser Ziel war die Beurteilung der Mikrovaskularisation und des antiangiogenetischen Effektes einer Thalidomidtherapie mittels dynamischer kontrastverstaerkter MRT (d-MRT) bei unterschiedlichen haematologischen Erkrankungen. Methodik. Bei 20

  13. Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing αβ+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies.

    Science.gov (United States)

    Muccio, Letizia; Bertaina, Alice; Falco, Michela; Pende, Daniela; Meazza, Raffaella; Lopez-Botet, Miguel; Moretta, Lorenzo; Locatelli, Franco; Moretta, Alessandro; Della Chiesa, Mariella

    2016-03-01

    We analyzed the impact of human cytomegalovirus infection on the development of natural killer cells in 27 pediatric patients affected by hematological malignancies, who had received a HLA-haploidentical hematopoietic stem cell transplantation, depleted of both α/β+ T cells and B cells. In line with previous studies in adult recipients of umbilical cord blood transplantation, we found that human cytomegalovirus reactivation accelerated the emergence of mature natural killer cells. Thus, most children displayed a progressive expansion of a memory-like natural killer cell subset expressing NKG2C, a putative receptor for human cytomegalovirus, and CD57, a marker of terminal natural killer cell differentiation. NKG2C(+)CD57(+) natural killer cells were detectable by month 3 following hematopoietic stem cell transplantation and expanded until at least month 12. These cells were characterized by high killer Ig-like receptors (KIRs) and leukocyte inhibitory receptor 1 (LIR-1) and low Siglec-7, NKG2A and Interleukin-18Rα expression, killed tumor targets and responded to cells expressing HLA-E (a NKG2C ligand). In addition, they were poor Interferon-γ producers in response to Interleukin-12 and Interleukin-18. The impaired response to these cytokines, together with their highly differentiated profile, may reflect their skewing toward an adaptive condition specialized in controlling human cytomegalovirus. In conclusion, in pediatric patients receiving a type of allograft different from umbilical cord blood transplantation, human cytomegalovirus also induced memory-like natural killer cells, possibly contributing to controlling infections and reinforcing anti-leukemia effects. Copyright© Ferrata Storti Foundation.

  14. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

    Science.gov (United States)

    Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

    2016-05-01

    Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

  15. 脐血移植治疗血液系统恶性疾病的临床研究进展%Clinical research progresses in umbilical cord blood transplantation in the treatment of hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    马立元; 郝思国

    2014-01-01

    异基因造血干细胞移植是治愈血液系统恶性疾病的唯一治疗手段,但常因难以获得人类白细胞抗原(human leukocyte antigen,HLA)相合的造血干细胞而受到限制。脐血含有丰富的造血干细胞,可作为造血干细胞移植的干细胞来源。它具有实物冻存、应用方便以及移植物抗宿主病较轻等优点。近年来,应用脐血移植成功地治疗恶性血液肿瘤的报道愈来愈多,脐血移植的基础研究也获得了较大的进步。现就脐血移植的应用现状、研究进展以及如何选择合适的脐血作一综述。%Allogeneic hematopoietic stem cell transplantation is the only treatment method to cure hemato-logic malignancies. However, dififculty in obtaining the human leukocyte antigen (HLA) match donors is a major lim-itation in this therapeutic strategy. Many studies have demonstrated that umbilical cord blood is rich in hematopoietic stem cells and can be used as a source of stem cells of hematopoietic stem cell transplantation. Growing evidence also supports the efifcacy of cord blood transplantation (CBT) to treat patients with haematological malignancies, and the number of CBTs is rapidly increasing. Compared to other sources of stem cells, umbilical cord blood is physical cryo-preserved. Therefore, it is very convenient for transplantation, particular for those who need to receive transplantation sooner. In addition, the incidence and severity of graft versus host disease(GVHD) in CBT are usually relatively lower. Herein, we review considerations regarding status, research progresses and selection of umbilical cord blood in CBT.

  16. Effect of itraconazole on treatment of invasive fungal infections in patients with hematological malignancies%伊曲康唑对恶性血液病患者侵袭性真菌感染的疗效分析

    Institute of Scientific and Technical Information of China (English)

    孙桂珍; 李学亮; 吉布强; 张海燕; 徐彧; 金北平; 张小红

    2012-01-01

    OBJECTIVE To explore the clinical efficacy of itraconazole in treatment of the invasive fungal infections in the patients with hematological malignancies. METHODS A total of 96 patients with hematological malignancies who enrolled hospitals from May 2009 to Dec 2011 were involved in the study, totally 45 cases which were suspected or established the fungal infections were given the sequential treatment of itraconazole; and other 51 patients who were consistent with the empirical treatment standard were given the intravenous itraconazole only, it was regarded as normal that the body temperature returned to normal ; the sequential treatment group adopted the sequential treatment with itraconazole, and it was regarded as effective when the clinical symptoms disappeared; the patients who were in accordance with the suspected or confirmed criteria during the treatment were transferred for the sequential treatment , then the clinical efficacy of the two groups was evaluated after one course. RESULTS Among 51 patients in the empirical treatment group, there were 9 suspected patients, totally 38 out of 42 cases in the empirical group responded well to iraconazole with the effective rate of 90. 48%; while the 51 out of 54 suspected cases in the sequential treatment group responded well with the effective rate of 94. 44%; there were no cases with renal dysfunction and 4 cases with liver abnormalities. CONCLUSION Itraconazole is effective and safe in the treatment of the invasive fungal infections in the patients with hematological malignancies, which is worth of the clinical promotion, but it is necessary to pay attention to the monitoring of the liver function.%目的 研究伊曲康唑在治疗恶性血液病患者侵袭性真菌感染的临床疗效.方法 将医院2009年5月-2011年12月收治的96例恶性血液病患者纳入研究,对于符合真菌感染拟诊病例纳入序贯治疗组(45例),符合真菌感染经验性治疗的病例纳入经验治疗组(51例),

  17. Hypercalcemia of malignancy: An update on pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Aibek E Mirrakhimov

    2015-01-01

    Full Text Available Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care.

  18. Refractory vasculitis

    NARCIS (Netherlands)

    Rutgers, Bram; Kallenberg, Cees G. M.

    2011-01-01

    Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side effects

  19. Refractory vasculitis

    NARCIS (Netherlands)

    Rutgers, Bram; Kallenberg, Cees G. M.

    Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side

  20. 妊娠合并血液系统肿瘤20例临床分析%Clinical Analysis of 20 Patients of Pregnancy Combined with Hematological Malignancy

    Institute of Scientific and Technical Information of China (English)

    金珍琳; 梁彬

    2012-01-01

    Objective To investigate the treatment and prognosis of hematological malignancy associated with pregnancy. Methods Clinical data of 20 patients in pregnancywith hematologicai malignancy, including 10 cases with acute leukemia ( AL) , 3 cases with chronic myeloid leukemia( CML) , 1 case with non - Hodgkin's lymphoma( NHL) and 6 cases with myelodysplastic syndrome( MDS) were analyzed retrospectively. Results The most treatment method was applying combined chemotherapy. Pregnancy outcome was as the following: 3 patients were ended with therapeutic abortion and 1 patient was ended with operation in first trimester,5 were induced abortion in second trimester,7 premature delivery,4 term delivery. During the follow - up,l patient was lost, 13 patient survived,6 died. The median follow - up duration was 45. 4months (from 5 months to 11 years) . Of 11 newborn,all were alive,and the median follow - up duration was 54. 5months ( from 3 months to 11 years). Two cases were hospitallized because of disease,and others all developed normally. Conclusion Hematologicai malignancy has adverse effect both on mother and infant,which tends to increasing the risk of pathological pregnancy,leading to premature infant, low birth weight infant, newborn dysplasia, even anemia and septicemia. Pregnant women usually have favorable outcome through timely diagnosis and appropriate treatment.%目的 探讨妊娠合并血液系统肿瘤的处理及预后.方法 回顾性分析妊娠合并血液系统肿瘤20例临床资料,其中急性白血病10例,慢性粒细胞白血病3例,恶性淋巴瘤1例,骨髓增生异常综合征6例.结果 ①治疗多采用联合化疗;②妊娠结局:孕早期治疗性流产3例,手术1例,中期引产5例,早产7例,足月分娩4例;③随访情况:失访1例,存活13例,死亡6例,中位随访时间45.4个月(5个月~11年);11例新生儿,目前均存活,中位随访时间54.5个月(3个月~11年),2例因病住院治疗,其余均正常.结论 血液系

  1. Artificial intelligence in hematology.

    Science.gov (United States)

    Zini, Gina

    2005-10-01

    Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems.

  2. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Bruun, B; Bangsborg, Jette Marie; Hovgaard, D;

    1988-01-01

    of coagulase-negative staphylococci was higher in the latter period while that of Staphylococcus aureus was lower. Of 67 strains of Enterobacteriaceae tested for an aminoglycoside, 6% were found to be resistant, whereas 8% of 48 Enterobacteriaceae strains were found to be cefotaxime resistant. Methicillin...

  3. 恶性血液病合并血流感染61例临床分析%Clinical Analysis of 61 Cases of Malignant Hematology with Bloodstream Infection

    Institute of Scientific and Technical Information of China (English)

    金凤波; 夏瑞祥; 金广霞; 吴炜; 刘飞

    2012-01-01

    的药物分别为亚胺培南、万古霉素及利奈唑胺.临床对该类患者及早正确使用敏感抗菌药物治疗,可有效控制感染,并可降低BSI导致恶性血液病患者的病死率.%Objective To study the characteristics,treatments and prognosis in the malignant hematology patients with bloodstream infection.Methods From January 2008 to December 2009,61 cases of malignant hematology with bloodstream infection patients,who were treated by department of blood transfusion in the First Affiliated Hospital of Anhui Medical University,were analyzed retrospectively.The antibiotic resistance rates and sensitivity rates of 72 non-duplicate pathogenic isolates were calculated,and the infection related factors and prognosis of malignant hematology with bloodstream infection patients were analyzed,through the issues of patients' neutrophil counts,days of hospitalization,age and initial antimicrobial treatment options.The x2 test was used to analyze the qualitative data,and the t-test was used to analyze the quantitative data.P<0.05 showed that the difference was statistically significant.Results The main pathogens of these 61 patients were Gram-negative bacterium.The total prevalence of extendedspectrum beta-lactamases (EBSLs)-producing strains in E.coli and Klebsiella isolates were 56.25% and 36.60%,respectively.The sensitive rates of ESBLs-producing strains of E.coli to Imipenem,Klebsiella to Imipenem,and Gram-positive cocci to Vancomycin and Linezolid were 100%.Compared with the patients whose neutrophils>0.5 × 109/L,the patients whose neutrophils<0.5 × 109/L were more susceptible to multiple infection (x2.455,P=0.02).Among the 60 patients,the multiple infection was significant different between hospitalization days <20 d and >20 d(x2 =7.576,P=0.006).The mortality was high in patients over the age of 60(x2=3.021,P=0.023).Before the blood culture results returning,the antimicrobial treatment average times of the 35 patients who had used

  4. Refractory and recurrent malignancies with arsenic trioxide MDT analysis influence on prognosis%难治及复发性恶性血液病采用三氧化二砷联合化疗对预后影响

    Institute of Scientific and Technical Information of China (English)

    安婕; 唐雯

    2014-01-01

    目的:观察三氧化二砷联合化疗方案治疗难治及复发性恶性血液病的效果。方法:随机从我院2009年6月~2014年6月收治的难治及复发性恶性血液病患者中抽取60例作为研究对象,根据治疗方案将其分为对照组和观察组,每组各30例。其中对照组使用单纯化疗方案治疗,观察组则使用三氧化二砷联合化疗的方案治疗,对比两组的临床效果和毒性反应。结果:经对比,观察组患者的总有效率为86.67%,显著高于对照组的66.67%,差异具有统计学意义(P<0.05)。同时,观察组的毒性反应发生率为30%,显著低于对照组的66.67%,差异具有统计学意义(P<0.05)。结论:对难治及复发性恶性血液病采用三氧化二砷联合化疗治疗具有显著疗效,降低不良反应,有助于改善患者的预后。%Objective: To explore the use of arsenic trioxide and combination in the treatment of refractory and the prognosis of recurrent malignancies effects and adverse reactions. Methods: Random from our hospital in June 2009~June 2014 patients with refractory and recurrent malignancies treated were extracted 60 cases as the research object, according to the treatment plan will be divided into control group and observation group, 30 cases in each group. , including control group using pure chemotherapy regimen for observation group joint solution with arsenic trioxide and chemotherapy treatment,compared two groups of clinical effect and toxic reaction. Results:By contrast, the observation group the total effective rate of the patients were 86.67%, significantly higher than that of control group 66.67%, and the difference is statistically significant(P<0.05). Incidence of toxic effects of at the same time, the observation group was 30%, significantly lower than the control group 66.67%, and the difference is statistically significant (P<0.05). Conclusion: The refractory and recurrent malignancies with

  5. The European Hematology Association Roadmap for European Hematology Research: a consensus document.

    Science.gov (United States)

    Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

    2016-02-01

    The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

  6. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  7. ABO血型不合异基因造血干细胞移植治疗恶性血液病%ABO-incompatible allogeneic hematopoietic stem cell transplantation for treating malignant hematologic diseases

    Institute of Scientific and Technical Information of China (English)

    邵晓雁; 欧阳建; 陈兵; 许景艳; 杨永公; 周敏

    2008-01-01

    合患者移植后成分输血过程未出现溶血反应,移植后也均未发生迟发性溶血反应.结论:ABO血型不合不影响造血干细胞移植的效果,且较为安全.%BACKGROUND:ABO-incompatibility between donor and recipient is not a barrier for Successful allogeneic hematopoietic stem cell transplantation even though it is well established that major ABO incompatibility may lead to prolonged destruction of donor-derived erythrocytos and prolonged transfusioil requirements.OBJECTIVE:To explore the effect of ABO.incompatible on clinical characteristics in allogeneic-hematopoietic stem cell transplantation.DESIGN:A retrospective observation.SETTING:Department of Hematology.the Affiliated Drum Tower Hospital of Nanjing University Medical School.PARTICIPANTS:Fourteen patients(11 males and 3 feiliales,aged 15-60 years old)with malignant hematologic diseases who received ABO-incompatible allogeneic hematopoietic stem cell transplantation in the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2002 to September 2007 Were recruited for this study.Of the 14 patients,7 were human leukocyte antigen(HLA).matched,and the other 7 were HLA-half-matched.Controls were 11 patients who received ABO-compatibility bone marrow transplantation during the same period.Written informed consents for receiving allogeneic hematopoietic stem cell transplantation were obtained from each reciplent.The donors were sibling sister,sibling brother.son and mother,and they all agreed to provide marrow for transplantation.T1lis experiment was given an approval by the Ethics Committees of the hospital.METHODS:Regimen conditioning:HLA-matched transplantation regimen conditioning consisted of busulfan(Bu)and cyclophosphamide(Cy).HLA-half-matched transplantation regimen conditioning adopted GIAC program from Beijing People's Hospital.The GIAC program consisted of 4 parts:G:granulocyte colony-stimulating factors used for donors;I:stronger immunosuppressive regimen

  8. A molecular biology and phase II study of imetelstat (GRN163L) in children with recurrent or refractory central nervous system malignancies: a pediatric brain tumor consortium study.

    Science.gov (United States)

    Salloum, Ralph; Hummel, Trent R; Kumar, Shiva Senthil; Dorris, Kathleen; Li, Shaoyu; Lin, Tong; Daryani, Vinay M; Stewart, Clinton F; Miles, Lili; Poussaint, Tina Young; Stevenson, Charles; Goldman, Stewart; Dhall, Girish; Packer, Roger; Fisher, Paul; Pollack, Ian F; Fouladi, Maryam; Boyett, James; Drissi, Rachid

    2016-09-01

    Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m(2), 12-24 h before surgery. Telomerase activity was evaluated in fresh tumor from surgery. Post-surgery and in the phase II study, patients received imetelstat IV (days 1 and 8 q21-days) at 285 mg/m(2). Imetelstat pharmacokinetic and pharmacodynamic studies were performed. Of two evaluable patients on the MB trial, intratumoral telomerase activity was inhibited by 95 % compared to baseline archival tissue in one patient and was inevaluable in one patient. Forty-two patients (40 evaluable for toxicity) were enrolled: 9 medulloblastomas, 18 HGG, 4 ependymomas, 9 diffuse intrinsic pontine gliomas. Most common grade 3/4 toxicities included thrombocytopenia (32.5 %), lymphopenia (17.5 %), neutropenia (12.5 %), ALT (7.5 %) and AST (5 %) elevation. Two patients died of intratumoral hemorrhage secondary to thrombocytopenia leading to premature study closure. No objective responses were observed. Telomerase inhibition was observed in peripheral blood mononuclear cells (PBMCs) for at least 8 days. Imetelstat demonstrated intratumoral and PBMC target inhibition; the regimen proved too toxic in children with recurrent CNS tumors.

  9. Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

    Science.gov (United States)

    2017-03-29

    Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

  10. Hematology in 2010: New therapies and standard of care in oncology.

    Science.gov (United States)

    DeVita, Vincent T; Canellos, George P

    2011-02-01

    2010 was not a year of survival breakthroughs in hematologic malignancies. However, in Hodgkin's disease and multiple myeloma new therapies emerged as the standard of care and nilotinib may be considered the treatment choice for newly diagnosed chronic myeloid leukemia.

  11. Trends in hematological cancer in the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Ocias, Lukas F; Larsen, Thomas S; Vestergaard, Hanne;

    2016-01-01

    BACKGROUND: The number of hematological malignancies is expected to increase as the Danish population ages within the next few decades. Despite this, data on the course of hematological cancers among the oldest patients are sparse with many intervention studies focusing on younger age groups. The...

  12. Certain new progresses in experimental hematology in China and more queries on mesenchymal stem cell research

    Institute of Scientific and Technical Information of China (English)

    唐佩弦

    2004-01-01

    @@ Since 1995 stem cell engineering and allied biological study in China has been developing more quickly, particularly in the field of experimental and clinical hematology. Some articles presented in this issue are mainly related to stem cell biology and immuno-hematology, particularly the immuno-mechanism in pathogenesis of blood diseases, immunotherapy for malignant blood diseases as well as novel methodology in laboratory.

  13. Evaluation of febrile neutropenic patients hospitalized in a hematology clinic

    Institute of Scientific and Technical Information of China (English)

    M ucahit Goruk; Mehmet Sinan Dal; Tuba Dal; Abdullah Karakus; Recep Tekin; Nida Ozcan; Orhan Ayyildiz

    2015-01-01

    Objective: To evaluate the febrile neutropenic patients with hematological malignancies hospitalized in hematology clinic with poor hygiene standards. Methods: A total of 124 patients with hematological malignancies (69 male, 55 female) hospitalized in hematology clinic with poor hygiene conditions depending on hospital conditions, between January 2007 and December 2010, were evaluated, retrospectively. Results: In this study, 250 febrile neutropenia episodes developing in 124 hospitalized patients were evaluated. Of the patients, 69 were men (56%) and 55 women (44%). A total of 40 patients (32%) had acute myeloid leukemia, 25 (20%) acute lymphoblastic leukemia, 19 (15%) non-Hodgkin's lymphoma, 10 (8%) multiple myeloma, and 8 (8%) chronic myeloid leukemia. In our study, 56 patients (22%) were diagnosed as pneumonia, 38 (15%) invasive aspergillosis, 38 (15%) sepsis, 16 (6%) typhlitis, 9 (4%) mucormy-cosis, and 4 (2%) urinary tract infection. Gram-positive cocci were isolated from 52%(n = 20), while Gram-negative bacilli 42%(n = 16) and yeasts from 6% (n = 2) of the sepsis patients, respectively. The most frequently isolated Gram-positive bacteria were methicillin-resistant coagulase-negative staphylococci (n=18), while the most frequently isolated Gram-negative bacteria was Escherichia coli (n=10). Conclusions: Febrile neutropenia is still a problem in patients with hematological ma-lignancies. The documentation of the flora and detection of causative agents of infections in each unit would help to decide appropriate empirical therapy. Infection control pro-cedures should be applied for preventing infections and transmissions.

  14. Outcomes following HSCT using fludarabine replacing cyclophosphamide as a new preconditioning regimen for treatment of hematologic malignancies%高危造血干细胞移植患者应用氟达拉滨替代环磷酰胺行预处理12例

    Institute of Scientific and Technical Information of China (English)

    王峰蓉; 许兰平; 刘代红; 陈欢; 张晓辉; 赵婷; 张圆圆; 刘开彦; 黄晓军

    2010-01-01

    Objective To evaluate the hypothesis of fludarabine replacing cyclophosphamide as a new myeloablative preconditioning for the treatment of malignant hematologic diseases in aged and/or intolerable patients receiving allogeniec stem cell transplantation (allo-HSCT). Methods Between January 2008 and November 2008,12 patients, who were intolerant to standard conditioning regimen, received allo-HSCT with HLA identical sibling (n = 9) or mismatched family donors (n = 3),including 1 case of acute lymphoblastic leukemia with Ph chromosome (Ph+ ALL) ,6 cases of acute myelogenous leukemia (AMD,3 cases of myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) and 2 cases of chronic myelogenous leukemia (CML). Stem cell sources were G-CSF mobilized peripheral blood alone (n = 1) ,or with G-CSF mobilized bone marrow (n - 11), with a median of 6. 68 (4. 35 - 7. 86) × 10~8/kg MNC and 1. 50 (0. 31 - 3. 91) × 10~6/kg CD34~+ cells. Eleven patients received revised busulfan and fludarabine regimen with/without antithymocyteglobulin(ATG),and the rest one received TBI and fludarabine regimen. GVHD prophylaxis included cyclosporin A, mycophenolate mofetil and methotrexate. Results Results All patients were well tolerated to the regimen without serious regimen related toxicity. The median time of ANC≥0. 5 × 10~9/L was day 17. 5 (11 - 23), and that of BPC≥20. 0 ×10~9/L was day 14. All patients except one got donor engraftment successfully and attained CR. With a median follow-up of 418 (62-554) days, 10 of 12 patients were alive and disease-free. Conclusion Fludarabine replacing cyclophosphamide as a new preconditioning regimen is well tolerated and safe for allo-HSCT, especially in older patients or/and those with severe concurrent medical conditions.%目的 探讨氟达拉滨(Flu)替代环磷酰胺(Cy)的预处理方案在异基因造血干细胞移植(allo-HSCT)的安全性和疗效.方法 接受allo-HSCT治疗的高龄(≥55岁)和(或)合并脏器功能

  15. Evaluation of febrile neutropenic patients hospitalized in a hematology clinic

    Directory of Open Access Journals (Sweden)

    Mücahit Görük

    2015-12-01

    Conclusions: Febrile neutropenia is still a problem in patients with hematological malignancies. The documentation of the flora and detection of causative agents of infections in each unit would help to decide appropriate empirical therapy. Infection control procedures should be applied for preventing infections and transmissions.

  16. Breakthroughs in hematology

    Directory of Open Access Journals (Sweden)

    Ulrich Jäger

    2013-03-01

    Full Text Available Hematology is a comprehensive discipline covering all oncological and non-oncological aspects of diseases of the blood or related organs. Hematological researchers have been pivotal in the progress which has been made in molecular diagnostics, targeted therapies, and hence personalized medicine. Besides the rapid scientific and clinical developments political and strategic issues have to be addressed: Education of medical personnel needs harmonization throughout Europe; patients all over Europe should have equal access to treatment, and further scientific progress has to be secured through funding on a national, European and international level despite economic restraints. The European Hematology Association (EHA pursues these issues with and for all European hematologists and patients.

  17. Diagnostic hematology of reptiles.

    Science.gov (United States)

    Stacy, Nicole I; Alleman, A Rick; Sayler, Katherine A

    2011-03-01

    The hematologic evaluation of reptiles is an indispensable diagnostic tool in exotic veterinary practice. The diversity of reptile species, their characteristic physiologic features, and effects of intrinsic and extrinsic factors present unique challenges for accurate interpretation of the hemogram. Combining the clinical presentation with hematologic findings provides valuable information in the diagnosis and monitoring of disease and helps guide the clinician toward therapy and further diagnostic testing. This article outlines the normal and pathologic morphology of blood cells of reptile species. The specific comparative aspects of reptiles are emphasized, and structural and functional abnormalities in the reptilian hemogram are described.

  18. Advances in hematology analyzers.

    Science.gov (United States)

    DeNicola, Dennis B

    2011-05-01

    The complete blood count is one of the basic building blocks of the minimum database in veterinary medicine. Over the past 20 years, there has been a tremendous advancement in the technology of hematology analyzers and their availability to the general practitioner. There are 4 basic methodologies that can be used to generate data for a complete blood count: manual methods, quantitative buffy coat analysis, automated impedance analysis, and flow cytometric analysis. This article will review the principles of these methodologies, discuss some of their advantages and disadvantages, and describe some of the hematology analyzers that are available for the in-house veterinary laboratory.

  19. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  20. Anticonvulsant drugs and hematological disease.

    Science.gov (United States)

    Verrotti, A; Scaparrotta, A; Grosso, S; Chiarelli, F; Coppola, G

    2014-07-01

    Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs.

  1. Clinical analysis of allogeneic hematopoietic stem cells transplantation for treatment of 15 children with malignant hematological diseases%异基因造血干细胞移植治疗儿童恶性血液病15例临床分析

    Institute of Scientific and Technical Information of China (English)

    王娴静; 董秀娟; 陈蕾; 马红霞; 焦雪丽; 吴书一; 刘文刚; 赵晓武

    2014-01-01

    目的 观察异基因造血干细胞移植(allo-HSCT)治疗儿童恶性血液病的疗效和相关并发症,探讨allo-HSCT治疗儿童恶性血液病的适应证.方法 回顾性分析15例接受allo-HSCT治疗的儿童恶性血液病患者的临床资料,其中13例为急性白血病,1例为慢性粒细胞白血病(加速期),1例为骨髓增生异常综合征(MDS-REBT);8例为亲缘供者,7例为非亲缘供者;11例行外周血造血干细胞移植治疗,4例行脐血造血干细胞移植治疗;6例为HLA配型全相合,9例为HLA配型不全相合.结果 15例患儿中生存7例,生存期为5个月~6年;5例因复发或重症感染放弃治疗;3例死亡.6例发生急性移植物抗宿主病(GVHD),包括Ⅰ度3例,Ⅱ、Ⅲ、Ⅳ度各1例,其中发生Ⅳ度急性GVHD患儿死亡.2例发生广泛性慢性GVHD,其中1例死亡,另1例生活质量严重受影响.结论 allo-HSCT是治疗儿童恶性血液病的重要方法,其并发症多、风险大,在防治并发症的同时,应严格把握allo-HSCT治疗儿童恶性血液病的适应证.%Objective To observe the therapeutic efficiency and associated complications of allogeneic hematopoietic stem cells transplantation (allo-HSCT) for treatment of children with malignant hematological disease.Methods Fifteen children with malignant hematological disease were subjected to allo-HSCT from Jan 2007 to Jan 2013.Among those 15 patients,13 cases were diagnosed as acute leukemia (AL),1 case as chronic myeloid leukemia (CML),and 1 case as myelodysplastic syndrome (MDS-RAEB).The clinical characters of all cases after transplantation were analyzed retrospectively.Results Seven cases survived from 5 months to 6 years after transplantation.Five cases abandoned treatment because of relapse or severe infections.Three cases developed grade Ⅰ acute graft-versus-host disease (aGVHD),three cases developed grade Ⅱ,Ⅲ and Ⅳ aGVHD respectively,and one case died of Ⅳ aGVHD.Two patients experienced extensive chronic graft

  2. Efficacy and toxicity of caspofungin in empirical treatment of invasive fungal infection in 32 patients with hematological malignancy%卡泊芬净经验性治疗血液疾病合并真菌感染32例临床观察

    Institute of Scientific and Technical Information of China (English)

    赵慧瑾; 钱樱; 陈丽; 沈杨

    2011-01-01

    目的:评估卡泊芬净经验性治疗血液疾病中性粒细胞减少合并疑似侵袭性真菌感染的安全性和疗效.方法:入选32例发热合并中性粒细胞缺乏、基础疾病为血液系统恶性肿瘤的患者.给予卡泊芬净经验性治疗,第1天70 mg,加入生理盐水250 mL,静脉滴注,持续1h,随后每天50 mg,加入生理盐水250 mL,静脉滴注,持续lh.治疗持续时间为体温好转、粒细胞缺乏恢复后继续使用3d;若患者粒细胞缺乏期间体温未好转,最长使用2周.结果:23例(72%)患者在中性粒细胞减少期间体温好转.主要不良事件是转氨酶升高(4/32)和低钾血症(4/32),经治疗均好转.3例患者死亡.所有患者治疗期间均未发生突破性真菌感染事件.结论:卡泊芬净是血液疾病合并真菌感染经验性治疗安全和有效的药物.%Objective To evaluate the safety and efficacy of caspofungin in empirical treatment of invasive fungal infection (IFI) in patients with hematological malignancy. Methods Thirty two patients with underlying hematological malignancy and febrile neutropenia were enrolled. Caspofungin 70 mg was infused intravenously for at least 1 h on the first day, and then reduced to 50 mg for successive days. The treatment lasted until 3 days after recovery of neutropenia. A maximum of 2 weeks of treatment was allowed if the patients didn't recover from fever. Results Twenty three patients (72%) had their temperature returned to normal during the period of neutropenia. The most frequent adverse events were elevation of transaminases (4/32) and hypokalemia (4/32). All the adverse events were reversible. Three patients died. No breaking through fungal infection events occurred. Conclusions Caspofungin is a safe and effective drug for the empirical treatment of hematological malignancy patients complicated with fungal infection.

  3. Detection of 11q23/MLL gene rearrangement in hematological malignancies with fluorescence in situ hybridization assay%间期荧光原位杂交技术检测恶性血液病的11q23/MLL基因重排

    Institute of Scientific and Technical Information of China (English)

    彭智; 冯文莉; 肖志坚; 周迎春; 刘光平; 刘基铎

    2008-01-01

    目的 分析伴有11q23/MLL基因重排的恶性血液病的细胞遗传学特点,探讨荧光原位杂交技术( FISH)在诊断及鉴定恶性血液病11q23/MLL基因重排中的价值.方法 用间期FISH分析11q23/MLL基因易位细胞的30例恶性血液病患者的核型特征, 用MLL双色分离探针绿色标记在 (5′MLL, 光谱绿) 和 (3′MLL, 光谱桔红).结果 应用常规细胞遗传学及间期FISH分析白血病患者30例,结果显示11q23+/MLL+患者9例(30.0%),11q23-/MLL+患者4例(13.3%),11q23+/MLL-患者2例(6.7%),11q23-/MLL-患者15例,检测到部分病例染色体核型分析与间期FISH方法检测11q23异常与MLL基因重排不一致.结论 FISH在检测11q23/MLL基因重排方面与传统的常规细胞遗传学相比具有检出率高的优势,能更有效、直观地分析恶性血液病的染色体异常,对于恶性血液病的诊断以及异常染色体的检出具有广泛的应用前景.%Objective To analyze the cytogenetical characteristic of 11q23/MLL gene rearrangement in hematological malignancies and to investigate the value of fluorescence in situ hybridization (FISH) assay in the diagnosis and appraisal of 11q23/MLL gene rearrangement.Methods FISH assay was performed to analyze the karyotypic characteristic of 11q23/MLL gene rearranged cells in 30 patients with hematological malignancies. The dual color probe was adopted. 5′MLL was labeled with spectrum green and 3′MLL labeled with spectrum orange.Results The incidence of 11q23+/MLL+ in acute leukemia (AL) patients was 30.0% (10 out of 30 cases) and 11q23-/MLL+ was 13.3% (4 cases) , and 11q23+/MLL- was 6.7% (2 cases) and the karyotype of 15 cases was normal. For some patients, different results were obtained by using conentional cytogenetical analysis and interphased FISH assay for detecting 11q23/MLL gene rearrangements.Conclusion FISH assay has greater advantage over cytogenetical study in the analysis of 11q23/MLL abnormality. It is also a promising tool in

  4. Systems hematology: an introduction.

    Science.gov (United States)

    Corey, Seth Joel; Kimmel, Marek; Leonard, Joshua N

    2014-01-01

    Hematologists have traditionally studied blood and its components by simplifying it into its components and functions. A variety of new techniques have generated large and complex datasets. Coupled to an appreciation of blood as a dynamic system, a new approach in systems hematology is needed. Systems hematology embraces the multi-scale complexity with a combination of mathematical, engineering, and computational tools for constructing and validating models of biological phenomena. The validity of mathematical modeling in hematopoiesis was established early by the pioneering work of Till and McCulloch. This volume seeks to introduce to the various scientists and physicians to the multi-faceted field of hematology by highlighting recent works in systems biology. Deterministic, stochastic, statistical, and network-based models have been used to better understand a range of topics in hematopoiesis, including blood cell production, the periodicity of cyclical neutropenia, stem cell production in response to cytokine administration, and the emergence of drug resistance. Future advances require technological improvements in computing power, imaging, and proteomics as well as greater collaboration between experimentalists and modelers. Altogether, systems hematology will improve our understanding of normal and abnormal hematopoiesis, better define stem cells and their daughter cells, and potentially lead to more effective therapies.

  5. Hematologic Complications of Pregnancy

    Science.gov (United States)

    Townsley, Danielle M.

    2013-01-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  6. The risk of melanoma and hematologic cancers in patients with psoriasis.

    Science.gov (United States)

    Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J

    2017-04-01

    The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  7. The Expression and Prognostic Value of the Peripheral Cannabinoid Receptor in Hermatological Malignancies

    NARCIS (Netherlands)

    N. Rayman (Nazik)

    2011-01-01

    textabstractNon-Hodgkin’s lymphoma’s (NHLs) are a heterogeneous group of hematological malignancies with a large variation in clinical presentation, morphological appearance and prognosis. The NHLs make up the largest group (40-50%) of all hematological malignancies. In 2007, 17.700 people in the Ne

  8. Hematological Changes Mimicking Myelodysplastic Syndrome Following Treatment for Osteosarcoma.

    Science.gov (United States)

    Løhmann, Ditte J A; Hasle, Henrik

    2015-04-01

    Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a feared long-term complication of pediatric cancer. Few osteosarcoma patients develop t-MDS/AML, but the frequency of hematological abnormalities after therapy is unknown. We reviewed biochemistry from osteosarcoma patients up to 3 years posttreatment. All children diagnosed with osteosarcoma at our department from 2006 to 2012 without relapse 1 month posttherapy were included (n=14). Serial blood counts posttherapy were analyzed. The median increase of mean corpuscular volume (MCV) from baseline was 8 fL 6 months posttherapy and remained >5 throughout follow-up. All posttreatment levels of MCV were above 90 fL in 5 patients. Six months posttherapy, the median difference for platelets, white blood count, and absolute neutrophil count had decreased from baseline. They remained under baseline throughout follow-up. Hemoglobin remained stable. Ferritin level was associated with increased MCV. MDS with monosomy 7 was diagnosed in 1 patient. Hypoplastic refractory cytopenia was found in another patient showing spontaneous normalization of hematologic values. More than a third of patients treated for osteosarcoma developed hematological abnormalities mimicking early MDS, but only 1 developed t-MDS/AML. Close hematological monitoring of patients recovering from osteosarcoma is essential and it is worth noting that hematological abnormalities are frequent and may be transitory.

  9. Hematologic manifestations of Helicobacter pylori infection

    Science.gov (United States)

    Campuzano-Maya, Germán

    2014-01-01

    Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

  10. 噬菌体展示技术在血液肿瘤诊断治疗中的应用%The Application of Phage Display Technology in the Diagnosis and Therapy of Hematological Malignancies

    Institute of Scientific and Technical Information of China (English)

    王沂; 张春明; 郝建秀; 宋娜玲; 刘金剑; 贺欣; 刘鉴峰; 王德芝

    2012-01-01

    Hematopoietic malignancies are serious hazard to public health. Presently, the most ideal method in diagnosing and treating hematopoietic malignancies is specific molecular diagnosis and targeted therapy. However, the most stubborn difficulty of this method lies in the screening of molecular target. Phage display technology, a powerful approach developed in recent decade, has many advantages, including high throughput screening, mimicking natural epitopes, easy purification, integrating protein function with its coding gene, etc. Phage display technology is widely used in the area of molecular biology, such as screening of functional peptides and proteins, the study of protein interactions, identification of antigens, screening of genetically engineered antibodies, etc, which is very fit for the screening of ideal targets. At present, the application of this technology in hematopoietic malignancies diagnosis and therapy is -focus on phage antibody library and phage random peptide library. This article will introduce the research findings of phage display technology in hematopoietic malignancies diagnosis and therapy, and look forward to the prospect of this technology in this area.%血液肿瘤即造血系统的恶性肿瘤,是一种严重危害公共健康的疾病.目前,血液肿瘤诊断治疗的最理想方法就是分子特异性诊断和靶向治疗,但该方法面临的最大困难就是分子靶点的选择.噬菌体展示技术是近十年发展起来的一种新的生物学技术,具有高通量筛选、模拟天然表位、易于纯化、将蛋白功能与编码基因相统一等优点,广泛应用于功能性蛋白质和多肽的筛选、蛋白质间的识别与相互作用、抗原表位的鉴定、基因工程抗体的筛选等多个分子生物学领域,非常适于理想靶点的选择.目前,噬菌体文库技术在血液肿瘤诊治中的应用主要集中在噬菌体抗体文库和噬菌体随机放库上.本文就噬菌体展示技术在血液

  11. Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Wilfred Delacruz

    2016-01-01

    Full Text Available Non-Hodgkin lymphomas (NHLs are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV- based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX, and cytarabine (hyperCVAD with intrathecal- (IT- MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD. The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted.

  12. Hematological dosimetry. Dosimetrie hematologique

    Energy Technology Data Exchange (ETDEWEB)

    Fluery-Herard, A. (CEA Centre d' Etudes de Fontenay-aux-Roses, 92 (FR). Direction des Sciences du Vivant)

    1991-01-01

    The principles of hematological dosimetry after acute or protracted whole-body irradiation are reviewed. In both cases, over-exposure is never homogeneous and the clinical consequences, viz medullary aplasia, are directly associated with the mean absorbed dose and the seriousness and location of the overexposure. The main hematological data required to assess the seriousness of exposure are the following: repeated blood analysis, blood precursor cultures, as indicators of whole-body exposure; bone marrow puncture, medullary precursor cultures and medullary scintigraphy as indicators of the importance of a local over-exposure and capacity for spontaneous repair. These paraclinical investigations, which are essential for diagnosis and dosimetry, are also used for surveillance and for the main therapeutic issues.

  13. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    Directory of Open Access Journals (Sweden)

    Emmanuel Gyan

    2015-02-01

    Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

  14. Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2017-02-14

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Indolent Non-Hodgkin Lymphoma; Malignant Lymphoma, Large Cell Type; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Non-Hodgkin Lymphoma

  15. Drug-Induced Hematologic Syndromes

    Science.gov (United States)

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  16. Drug-Induced Hematologic Syndromes

    Directory of Open Access Journals (Sweden)

    David M. Mintzer

    2009-01-01

    Full Text Available Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications.

  17. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ribera JM

    2015-06-01

    Full Text Available Josep-Maria Ribera, Albert Ferrer, Jordi Ribera, Eulàlia GenescàClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, SpainAbstract: The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE® monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin’s lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R acute lymphoblastic leukemia (ALL and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.Keywords: acute lymphoblastic leukemia, relapsed/refractory, BiTE® monoclonal antibodies, blinatumomab

  18. Evaluation of febrile neutropenic patients hospitalized in a hematology clinic

    Institute of Scientific and Technical Information of China (English)

    Mcahit; Grk; Mehmet; Sinan; Dal; Tuba; Dal; Abdullah; Karakus; Recep; Tekin; Nida; zcan; Orhan; Ayyildiz

    2015-01-01

    Objective:To evaluate the febrile neutropenic patients with hematological malignancies hospitalized in hematology clinic with poor hygiene standards.Methods:A total of 124 patients with hematological malignancies(69 male,55 female)hospitalized in hematology clinic with poor hygiene conditions depending on hospital conditions,between January 2007 and December 2010,were evaluated,retrospectively.Results:In this study,250 febrile neutropenia episodes developing in 124 hospitalized patients were evaluated.Of the patients,69 were men(56%)and 55 women(44%).A total of 40 patients(32%)had acute myeloid leukemia,25(20%)acute lymphoblastic leukemia,19(15%)non-Hodgkin’s lymphoma,10(8%)multiple myeloma,and 8(8%)chronic myeloid leukemia.In our study,56 patients(22%)were diagnosed as pneumonia,38(15%)invasive aspergillosis,38(15%)sepsis,16(6%)typhlitis,9(4%)mucormycosis,and 4(2%)urinary tract infection.Gram-positive cocci were isolated from 52%(n=20),while Gram-negative bacilli 42%(n=16)and yeasts from 6%(n=2)of the sepsis patients,respectively.The most frequently isolated Gram-positive bacteria were methicillin-resistant coagulase-negative staphylococci(n=18),while the most frequently isolated Gram-negative bacteria was Escherichia coli(n=10).Conclusions:Febrile neutropenia is still a problem in patients with hematological malignancies.The documentation of the flora and detection of causative agents of infections in each unit would help to decide appropriate empirical therapy.Infection control procedures should be applied for preventing infections and transmissions.

  19. The evaluation and optimal use of rituximab in lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Smolewski P

    2012-01-01

    Full Text Available Tadeusz Robak1, Pawel Robak2, Piotr Smolewski21Department of Hematology, 2Experimental Hematology, Medical University of Łódź, Łódź, PolandAbstract: Rituximab is an IgG1, chimeric monoclonal antibody (mAb containing murine light- and heavy-chain variable-region sequences and human constant-region sequences. Rituximab targets the CD20 molecule expressed on normal and malignant B-lymphocytes. At present, rituximab is the most important mAb of clinical value in patients with B-cell lymphoid malignancies. Since approval in 1997, rituximab has become widely used in chronic lymphocytic leukemia (CLL, follicular lymphoma (FL, mantle cell lymphoma (MCL, and diffused large B-cell lymphoma (DLBCL when combined with chemotherapy. Currently, rituximab is commonly combined with first-line chemotherapy for FL and should be offered as maintenance therapy to all appropriate patients with this disease. Randomized Phase III trials demonstrated the superiority of rituximab added to CHOP chemotherapy against CHOP chemotherapy alone in patients with DLBCL. Rituximab alone has limited activity in MCL but can be used in MCL in combination with chemotherapy, despite the benefits not being as impressive as when used against other lymphoma entities. In addition, for the less frequent B-cell lymphomas, small series show considerable activity for most of these entities. Fludarabine and rituximab combination therapies in CLL yielded promising results in several studies. Two large Phase III randomized trials demonstrated the superiority of chemoimmunotherapy with rituximab compared with chemotherapy alone in previously untreated and refractory/relapsed patients with CLL. Therefore, it can be concluded that rituximab, with only few exceptions, can generally be accepted as a standard component of anti B-cell non-Hodgkin's lymphoma therapies. In this review, the pharmacology, mode of action, pharmacokinetics, and current place in the therapy of B-cell lymphoid

  20. Hematologic manifestations of babesiosis.

    Science.gov (United States)

    Akel, Tamer; Mobarakai, Neville

    2017-02-15

    Babesiosis, a zoonotic parasitic infection transmitted by the Ixodes tick, has become an emerging health problem in humans that is attracting attention worldwide. Most cases of human babesiosis are reported in the United States and Europe. The disease is caused by the protozoa of the genus Babesia, which invade human erythrocytes and lyse them causing a febrile hemolytic anemia. The infection is usually asymptomatic or self-limited in the immunocompetent host, or follows a persistent, relapsing, and/or life threatening course with multi-organ failure, mainly in the splenectomized or immunosuppressed patients. Hematologic manifestations of the disease are common. They can range from mild anemia, to severe pancytopenia, splenic rupture, disseminated intravascular coagulopathy (DIC), or even hemophagocytic lymphohistiocytosis (HLH). A 70 year old immunocompetent female patient living in New York City presented with a persistent fever, night sweats, and fatigue of 5 days duration. Full evaluation showed a febrile hemolytic anemia along with neutropenia and thrombocytopenia. Blood smear revealed intraerythrocytic Babesia, which was confirmed by PCR. Bone marrow biopsy was remarkable for dyserythropoiesis, suggesting possible HLH, supported by other blood workup meeting HLH-2004 trial criteria. Human babesiosis is an increasing healthcare problem in the United States that is being diagnosed more often nowadays. We presented a case of HLH triggered by Babesia microti that was treated successfully. Also, we presented the hematologic manifestations of this disease along with their pathophysiologies.

  1. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema.

    Science.gov (United States)

    Fujita, Kohei; Kim, Young Hak; Nakatani, Koichi; Mio, Tadashi

    2015-10-01

    Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases.

  2. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema

    OpenAIRE

    Fujita, Kohei; KIM, YOUNG HAK; Nakatani, Koichi; Mio, Tadashi

    2015-01-01

    Key Clinical Message Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases.

  3. 嵌合抗原受体-T细胞免疫治疗在血液系统恶性肿瘤中的应用进展%Application of CAR-T Cell Immunotherapy in the Treatment of Hematological Malignancy

    Institute of Scientific and Technical Information of China (English)

    克晓燕

    2016-01-01

    Chimeric antigen receptor(CAR)connects single - chain variable fragment and activation motif of T cells, which allows modified T cells possess dual functions of recognizing tumor antigens in an MHC unrestricted way and killing the target cells. The intracellular structures of CAR has changed over time,from the first generation with the expression of single signal molecule,to the second and third generation adding one or two and multiple costimulatory endodomains,and to the fourth generation combining with the domains of coding CAR and/ or the promoter,and suicide gene. They enhance and regulate the persistence and cytotoxicity of modified T cells. This paper summarized the available data on the principle of CAR-T cell immunotherapy,its application in the treatment of hematological malignancy,and the main adverse reactions and response measures. It was found that chimeric antigen receptor - T(CAR-T)cells have received better therapeutic effect in many types of hematological malignancy,remarkably for the CAR-T cell immunotherapy targeting CD19;patients who adopt cell immunotherapy have prolonged survival,improved quality of life,and less adverse reactions. The main adverse reactions of CAR-T cell immunotherapy are on - target toxicity and cytokine release syndrome,which must be paid more attention.%嵌合抗原受体(CAR)将单链抗体可变区与 T 细胞的活化基序相融合,使其修饰的 T 细胞具有非主要组织相容性复合物(MHC)限制性识别肿瘤抗原及杀伤靶细胞的双重功能。CAR 细胞内区的结构从表达单一信号分子的第1代,发展为添加1个及2个以上共刺激分子的第2代和第3代以及增加了编码 CAR 和/或其启动子、自杀基因等的第4代,使 T 细胞在体内的存活时间和杀伤能力明显增强且能够调控。本文就CAR-T细胞免疫治疗的原理、在血液系统恶性肿瘤中的应用以及主要不良反应和应对措施进行分析,发现应用CAR

  4. 重组人血小板生成素治疗血液肿瘤化疗后血小板减少的系统评价%Meta-analysis of Recombinant Human Thromobopoietin in the Treatment of Hematology Malignance Chemotherapy Induced Thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    黄琳; 刘一; 任晓蕾; 赵立波

    2011-01-01

    目的:评价重组人血小板生成素(rhTPO)治疗成人血液肿瘤化疗后血小板减少的有效性与安全性.方法:采用循证医学的方法,计算机检索CBM、CNKI 、MEDLINE、EMBASE、Cochrane图书馆临床对照试验资料库等数据库,收集rhTPO治疗成人血液肿瘤化疗后血小板减少的临床研究证据.结果:共纳入7篇文献.与对照组相比,rhTPO试验组血小板计数最低值、血小板计数恢复的最高值、血小板<50×109·L-1的持续天数、血小板恢复≥100× 109· L-1的天数以及血小板输注量加权均数差值(WMD)(95%可信区间(CI))分别为1.06(-0.08,2.20)、67.19 (32.1, 101.58)、-3.35(-4.51,-2.18)、-2.97(-4.63,-1.32)、- 2.58(-4.92,-0.24),不良反应发生率相对危险度(RR)(95%CI)为4.69( 1.90,11.58).结论:现有研究显示,在治疗成人血液肿瘤化疗后血小板减少方面,rhTPO能够提高血小板恢复的最高值和增加值,缩短化疗后血小板<50×109·L-1的持续天数,加快血小板的恢复速度,并间接减少血小板输注量,且不良反应轻微.然而,目前临床试验设计存在不足,尚需进行设计良好的大样本研究验证.%OBJECTIVE: To evaluate the efficacy and safety of recombinant human thromobopoietin (rhTPO) in the treatment of hematology malignance chemotherapy induced thrombocytopenia (RITP). METHODS: Literature analysis based on evidence-based medicine was performed. The databases of controlled clinical trials including CBM, CNK1, MEDLINE, EMBASE and Cochrane Library were retrieved to collect clinical research documents on the efficacy of rhTPO in the treatment of RITP. RESULTS: 7 studies were included. Meta-analysis showed: compared with control group, WMD (95% CI in rhTPO group of minimum platelet count, maximum platelet count recovery, duration of platelet count<50×109·L-1, duration of platelet recovery≥100× 109·L-1 and platelet transfusion amount were 1.06 (-0.08,2.20),67.19(32.1, 101.58),-3

  5. Safety and efficacy of a combination therapy with Revlimid, Adriamycin and dexamethasone (RAD) in relapsed/refractory multiple myeloma (MM): a single-centre experience

    OpenAIRE

    Caravita, Tommaso; Siniscalchi, Agostina; Tendas, Andrea; Cupelli, Luca; Ales, Micaela; Perrotti, Alessio; Niscola, Pasquale; De Fabritiis, Paolo

    2010-01-01

    Safety and efficacy of a combination therapy with Revlimid, Adriamycin and dexamethasone (RAD) in relapsed/refractory multiple myeloma (MM): a single-centre experience phone: +39-065-1008983 (Siniscalchi, Agostina) (Siniscalchi, Agostina) Department of Hematology S. Eugenio Hospital, ?Tor Vergata? University - Piazzale dell?Umanesimo, 10 - 00100 - Rome - ITALY (Caravita, Tommaso) Department of Hematology S. Eugenio Hospital, ?Tor Vergata? University - Piazz...

  6. Measuring symptoms as a critical component of drug development and evaluation in hematological diseases

    OpenAIRE

    Williams, Loretta A.; Yucel, Emre; Cortes, Jorge E.; Cleeland, Charles S.

    2013-01-01

    With the rapid development of new therapies for patients with hematological malignancies, there is an increasing need for patient report of symptom status during all phases of drug testing. The patient’s perspective on new treatments reflects treatment tolerability as well as symptom benefit, and may assist patients and clinicians in choosing treatments. Inclusion of patient-reported outcomes, more common in solid-tumor than hematological trials, provides early information about symptoms to g...

  7. 卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染的临床观察%Clinical study on neutropenia complicated with deep fungal infection in patients with malignant hematological diseases after chemotherapy.

    Institute of Scientific and Technical Information of China (English)

    汪玉芳; 陈世明

    2013-01-01

    目的 分析卡泊芬净治疗恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染临床效果及安全性.方法 选取2009年3月至2012年5月收治恶性血液病化疗后中性粒细胞缺乏合并深部真菌感染患者50例,采用随机数字表法分为两性霉素B组和卡泊芬净组,分别采用两性霉素B和卡泊芬净静脉滴注治疗;比较两组患者临床治疗总有效率及不良反应发生率等.结果 两性霉素B组总有效率(72.0%)与卡泊芬净组患者(76.0%)比较无显著差异(P>0.05);两性霉素B组不良反应发生率(36.0%)明显高于卡泊芬净组(P 0.05 ). The incidence rate of adverse reactions in caspofungin group ( 0% )was significantly lower than that of amphotericin B group( 36.0% )( P >0.05 ). Conclusion Caspofungin in treatment of deep fungal infection complicated with neutropenia in patients with malignant hematological diseases after chemotherapy has perfect therapeutic efficacy and few adverse reactions.

  8. Application Study on Self-management Programs in the PICC Home Self-management in Patients with Hematologic Malignancy%自我管理项目在恶性血液病患者PICC居家自我护理中的应用探讨

    Institute of Scientific and Technical Information of China (English)

    华银玲

    2016-01-01

    目的:探讨恶性血液病外周静脉置入中心静脉导管患者接受自我管理项目干预在其居家自我护理中的应用效果。方法两组均行PICC并于化疗间歇停止住院返回家中,对照组仅给予针对家庭常规宣教干预;研究组在常规宣教基础上增加自我管理干预措施。记录两组恶性血液病患者干预前后自我护理能力变化情况、PICC相关不良反应发生情况。结果两组干预前具有并无显著差异的自我护理能力(P>0.05);经不同干预后两组ESCA量表评分均较之前有所提高,研究组ESCA量表评分改善效果更优(P0.05), after different interventions, the ESCA scale scores of the two groups were improved, and the ESCA scale score improvement effect in the research group was better(P<0.05), the incidence rate of PICC relevant adverse reaction in the research group was only 8.89% and 28.89% in the control group, and the difference had statistical significance (P<0.05). Conclusion The targeted self-management program intervention measures for patient with hematologic malignancy can obviously improve the home self-nursing ability, which is conducive to ensuring the use safety of PICC and prognosis effect.

  9. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    Science.gov (United States)

    2017-06-30

    Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

  10. 卡泊芬净治疗40例恶性血液病患者合并侵袭性真菌感染临床研究%Clinical study of caspofungin in the treatment of invasive fungal infection in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    夏亮; 夏瑞祥; 曾庆曙; 杨明珍; 王永庆

    2013-01-01

    Objective To evaluate the efficacy and safety of caspofungin in the treatment of invasive fungal infection (IFI) in patients with hematologic malignancies. Methods Data of 40 hematologic malignancies patients received caspofungin (with caspofunjin at a dose of 70 mg in the first day,and then at a dose of 50 mg/d) treatment between January 2010 and December 2011 were retrospectively reviewed.Adverse events and the efficacy were investigated. Results Of the 40 patients, 26 were male and 14 were female, with a median age of 38 years old. One candida glabrata and 1 candida tropical were positive (blood culture);two cases were aspergillus positive (pleural effusion culture). Ten cases of qualified sputum culture were positive, including 4 candida albicans, 2 aspergillus, 2 candida glabrata, 1 candida krusei, and 1 candida tropical. Four cases were proven IFI and 10 probable IFI, 26 possible IFI. In all 40 patients, 17 cases were cured (42.5%) and 8 cases markedly improved (20.0%), 8 cases were progressive(20.0%), and 7 cases were ineffective(17.5%), with an overall effective rate of 62.5%. In effectively treated patients, the median time of fever clearance was 4.5 (l~ll)d. In the group of initial treatment, 17 cases were effective in 21 with an effective rate of 81.0%; in the saving group, 8 cases were effective in 19 with an effective rate of 42.1%. In the process of caspofun— gin treatment, treatment—related adverse reactions were mostly treated and had recoverability. Conclusion Caspofungin may be an effective and safe drug to treat IFI in patients with hematologic malignancies, and can be used as the first choice of antifungal therapy in IFI patients.%目的 探讨卡泊芬净治疗恶性血液病合并侵袭性真菌感染(IFI)的疗效及安全性.方法 回顾分析2010 年1 月至2011年12 月40 例接受卡泊芬净治疗(首日70 mg/d,之后50 mg/d,疗程依患者病情而定)恶性血液病患者的临床资料,观察患者

  11. Clinical observation of allogeneic hematopoietic stem cell transplantation for 20 patients with hematologic malignancies%异基因造血干细胞移植治疗恶性血液病20例临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    潘鹏吉; 王季石; 孙志强; 卢英豪; 李梦醒; 赵鹏; 龙正美

    2012-01-01

    Objective To evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) in treatment of hematologic malignancies and observe hematopoietic reconstitution, graft versus host disease (GVHD) occurrence,transplant-related complications and the outcome of disease.Methods 20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39 (8-59) years. Mobilization of donor’ s stem cells using rhG-CSF program 3 days before transplantation.Conditioning regimen:the patients with HLA-matched used modified Bu/Cy programs,the patients with HLA-mismatched (with 1 to 3 loci mismatched) used the modified Bu/Cy+ ATG program; the patient with T-ALL and the patient with MM used Flu+Bu/Cy program. GVHD prevention programs: mycophenolate mofetil + cyclosporine + short course methotrexate. Results 20 patients were successfully engrafted,the median time of absolute neutrophil count (ANC) > 0.5×109/L was 13 (12-17) days,the median time of Plt > 20×109/L was 16 (12-23) days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CDh cells > 2.5× 106/kg (recipient body weigh) or the collected amount of mononuclear cell > 5.0×10s/kg (recipient body weigh).No severe hemolytic reaction occurred in 11 cases of blood group incompatibility between donor and recipient after transplantation,11 cases (55 %) developed acute GVHD (aGVHD):4 cases Ⅰ degree aGVHD,4 cases Ⅱ degree aGVHD,2 cases Ⅲ degree aGVHD,1 case Ⅳ degree aGVHD,all patients were improved after treatment.All patients attained complete remission (CR) after transplantation.Follow-up 6 (2-14) months,1 patient died in 5 months after transplantation because of leukemia relapse, 1 case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD (cGVHD) and multiple organ failure

  12. [Treatment of hematologic neoplasms during pregnancy].

    Science.gov (United States)

    Tartas, Norma E; Foncuberta, María C; Avalos, Julio C Sánchez

    2007-01-01

    The most common hematological malignancy in pregnant patients is Hodgkin's lymphoma, but other diseases such as chronic and acute leukemia or non Hodgkin's lymphoma have also been reported. In the last decade, new drugs have changed the prognostic of acute promyelocytic leukemia, chronic myeloid leukemia and non Hodgkin's lymphoma. Herein we present updated information on drugs and treatments, new developments, mechanism of action, clinical application, experience on treatment outcomes, adverse effects and teratogenesis, with the objective of orienting hematologists, oncologists and pediatricians. The medical team should offer the most efficient treatment available in order to achieve cure or remission of the disease, and also inform on possible risks for the mother and the fetus, as well as those derived from the delay in treatment application.

  13. Developing Refractories for Exporting

    Institute of Scientific and Technical Information of China (English)

    PANShang-xin

    1996-01-01

    The total output of China refractory products and export volume of China refractory raw materials rank the first in the world,In future the task is to improve the quality of the products to enlarge the variety and to expand export.

  14. Silica Refractory Bricks

    Institute of Scientific and Technical Information of China (English)

    Yu Lingyan; Peng Xigao

    2011-01-01

    @@ 1.Scope This standard specifies the classification,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of silica refractory bricks.This standard is applicable to silica refractory bricks with single weight≤40 kg.

  15. Pediatric hematology and oncology in Iran.

    Science.gov (United States)

    Alebouyeh, Mardawig

    2005-01-01

    Pediatric hematology and oncology (PHO) is a rapidly expandingfield. It has been our goal to meet the needs and increasing demands for comprehensive medical care of children suffering from chronic blood diseases and malignancies. In the past decade we have been able expand and optimize the PHO services throughout Iran, in general and in respect to their prevalence and clinical importance, by trained pediatric hematologist-oncologists, pediatric surgeons and improved para clinical facilities. Major beta-thalassemics receive blood transfusion and chelation therapy according to the current standards mostly at regional blood banks centers. To curb major beta-thalassemia a premarital screening program has been enacted and abortion has been legitimized if major thalassemia is diagnosed by CVS. Hemophiliacs are supervised and treated as indicated by Iranian Hemophilia Comprehensive Care Centers (IHCCC). Screening for transfusion related complications and transmitted viral diseases (HBV, HCV and HIV) in both cohorts are carried out in regular intervals and necessary management will be then carried out as indicated at respective specialized units. Childhood malignancies are treated according to protocols adopted from accredited institutions in the USA and Europe, with almost comparable results. BMT is available for selected patients with beta-thalassemia or malignancies. By going to public we have been able to rise general awareness about chronic blood diseases and childhood malignancies and have initiated establishment of parents groups and formation of NGOs to support these children and their families. Foundation of Iranian Society of Pediatric Hamatology and Oncology (ISPHO) in the year 2000 has been another step forward to consolidate and coordinate the available manpower and facilities. By evaluation of the country's main problems and shortcomings and conduction of collaborative studies and operation planning one will succeed to get the expected feedback and

  16. Development of improved refractories

    Energy Technology Data Exchange (ETDEWEB)

    Wereszczak, A.A.; Ferber, M.K.; Liu, K.C. [Oak Ridge National Lab., TN (United States); Moore, R.E. [Univ. of Missouri, Rolla, MO (United States)

    1997-04-01

    The goal of the proposed project is to provide expertise and facilities for the high temperature mechanical properties characterization of refractory materials which are of interest to the US DOE`s Office of Industrial Technologies Advanced Industrial Materials Project. Initially the project would establish dedicated refractory testing facilities which would be capable of generating representative engineering creep and high temperature modulus of elasticity (MOE) data to a temperature of 3300{degrees}F (1815{degrees}C) in ambient air. The generated engineering creep and MOE data would serve R&D requirements of refractories-manufacturers and its glass-manufacturer end-users and designers. The relevance of this effort to the refractory and glass-making industries would be ensured by coordinating the research activities through a membership with Alfred University`s Center for Glass Research (CGR) Satellite Center at the University of Missouri-Rolla (UMR), an NSF Center. Valid engineering creep and high temperature MOE data currently do not exist for almost all commercial refractories. Refractory end-users such as glass-manufacturers require such data for efficient and economical design of their various glass-melting furnace superstructures (e.g., furnace crowns). Refractories in glass production furnaces may be subjected to extreme temperatures as high as 3200{degrees}F (1760{degrees}C). With the simultaneous imposition of mechanical and thermal stresses, creep deformation of the refractory material will assuredly occur as a consequence. Designers must ensure that the structural integrity is maintained, so these high temperature deformations must be considered for successful glass furnace superstructure design. These criteria can only be satisfied with the utilization of representative engineering creep and high temperature MOE data for the refractory materials that are chosen for the design of the refractory superstructures.

  17. Coexistence of Essential Thrombocythemia, Iron-Refractory Iron Deficiency Anemia and Renal Cell Carcinoma

    Science.gov (United States)

    Tekgündüz, Emre; Altuntaş, Fevzi

    2016-01-01

    Essential thrombocythemia (ET) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm. It is characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow with JAK2V617F mutation. Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder, which is mainly characterized by iron deficiency anemia not responding to oral iron intake, but partially responding to parenteral iron therapy. Recently, it has been shown that IRIDA has stemmed from mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (matriptase-2) expressed by the liver. Renal cell carcinoma (RCC) accounts for 2-3% of all cancers. As the most common solid lesion in the kidneys, it represents approximately 90% of all renal malignancies. Approximately 30% of patients with symptomatic RCCs seem to display paraneoplastic syndromes. The symptom that may result from erythrocytosis is the most well-known paraneoplastic hematological event. Here, we report a patient who presents with coexistence of RCC and thrombocytosis, which hasn’t been caused by hormonal factors that are produced in tumor cells. This patient has been therefore diagnosed with ET. The patient who was expected to display RCC with polycythemia, conversely present with IRIDA. PMID:27103977

  18. Coexistence of essential thrombocythemia, iron-refractory iron deficiency anemia and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sinem Namdaroğlu

    2016-03-01

    Full Text Available Essential thrombocythemia (ET is a Philadelphia chromosome (Ph-negative myeloproliferative neoplasm. It is characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow with JAK2V617F mutation. Iron-refractory iron deficiency anemia (IRIDA is an autosomal recessive disorder, which is mainly characterized by iron deficiency anemia not responding to oral iron intake, but partially responding to parenteral iron therapy. Recently, it has been shown that IRIDA has stemmed from mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (matriptase- 2 expressed by the liver. Renal cell carcinoma (RCC accounts for 2-3% of all cancers. As the most common solid lesion in the kidneys, it represents approximately 90% of all renal malignancies. Approximately 30% of patients with symptomatic RCCs seem to display paraneoplastic syndromes. The symptom that may result from erythrocytosis is the most wellknown paraneoplastic hematological event. Here, we report a patient who presents with coexistence of RCC and thrombocytosis, which hasn’t been caused by hormonal factors that are produced in tumor cells. This patient has been therefore diagnosed with ET. The patient who was expected to display RCC with polycythemia, conversely present with IRIDA.

  19. Treatment of refractory anemia with ring sideroblasts associated with marked thrombocytosis with lenalidomide in a patient testing negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations

    Directory of Open Access Journals (Sweden)

    Ryan Keen

    2016-11-01

    Full Text Available Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts. Herein we present the case of a 68-year-old African American woman with RARS-T who tested negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations. Her treatment with lenalidomide therapy resulted in a five-year durable complete clinical response.

  20. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1996-08-15

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated.

  1. Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.; Barofsky, D.F.

    1991-12-31

    This progress report describes accomplishments under four headings, namely: The study of the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (MAb) targeting tumor associated antigens; Effects of lysosomotropic amines, carboxylic ionophores, and thioamides on the retention of radiolabeled MAbs by tumor cells; Subcellular site of radioimmunoconjugate degradation and the sizes of fragments generated by intracellular metabolism of radiolabeled antibodies; and Patterns of metabolic degradation of radioimmunoconjugates made with different techniques and with different radionuclides.

  2. The molecular mechanism of thalidomide analogs in hematologic malignancies.

    Science.gov (United States)

    Lindner, Stefanie; Krönke, Jan

    2016-12-01

    Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells. The underlying molecular mechanisms for these pleiotropic effects remained obscure until the identification of the cereblon (CRBN) E3 ubiquitin ligase as the primary target of thalidomide and its analogs in 2010. Binding of thalidomide or lenalidomide increases the affinity of CRBN to the transcription factors IKZF1 and IKZF3 and casein kinase 1α (CK1α). Ubiquitination and degradation of these neo-substrates results in IL-2 release and growth arrest of multiple myeloma and MDS cells. The discovery of this previously undescribed mechanism for an approved drug provides a proof-of-concept for the development of new therapeutics that exploit ubiquitin ligases for specific degradation of disease-associated proteins.

  3. Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

    Science.gov (United States)

    2009-01-28

    Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Paroxysmal Nocturnal Hemoglobinuria; Hodgkin's Lymphoma; Non-Hodgkin Lymphoma

  4. Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Jessica M. McDaniel

    2012-01-01

    Full Text Available The immunomodulatory agent, lenalidomide, is a structural analogue of thalidomide approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS and multiple myeloma (MM. This agent is also currently under active investigation for the treatment of chronic lymphocytic leukemia (CLL and non-Hodgkin’s lymphoma (NHL, as well as in drug combinations for some solid tumors and mantle cell lymphoma (MCL. Although treatment with lenalidomide has translated into a significant extension in overall survival in MM and MDS and has superior safety and efficacy relative to thalidomide, the mechanism of action as it relates to immune modulation remains elusive. Based on preclinical models and clinical trials, lenalidomide, as well as other structural thalidomide derivatives, enhances the proliferative and functional capacity of T-lymphocytes and amplifies costimulatory signaling pathways that activate effector responses and suppress inflammation. This paper summarizes our current understanding of T- and natural killer (NK cell pathways that are modified by lenalidomide in hematopoietic neoplasms to inform future decisions about potential combination therapies.

  5. Unexpected second primary malignancies detected by f-18 FDG PET/CT during follow-up for primary malignancy: Two case report

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji In; Lee, Eun Seong; Kim, Tae Sung; Kim, Seok Ki [Nuclear Medicine, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2015-03-15

    As the survival rate of cancer patients has increased over the last few decades, the risk of cancer survivors developing second primary malignancies has gained attention. We report two rare cases of second primary hematologic malignancy detected by 18F-fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) during follow-up for primary solid malignancies. Acute lymphoblastic leukemia developed in a breast cancer patient and non-Hodgkin lymphoma in an anal cancer patient. F-18 FDG PET/CT findings led to the diagnosis of unexpected second primary hematologic malignancy in cancer survivors in these two cases.

  6. Malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Suzanne Alkul

    2016-04-01

    Full Text Available Seventy percent of patients with malignant mesothelioma have had exposure to asbestos fibers. Other patients without this exposure have had chronic pleural inflammation or received radiation to the thorax. Occasionally patients present with no obvious exposure history relevant to the development of malignant mesothelioma. This diagnosis needs to be in the differential diagnosis of all patients with unexplained pleural disease.

  7. Pleural malignancies.

    Science.gov (United States)

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.

  8. Fireclay Refractory Bricks

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiaohui

    2010-01-01

    @@ 1 Scope This standard specifies the classification,brand,shape,dimension,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of fireclay refractory bricks.

  9. Consensus strategy to quantitate malignant cells in myeloma patients is validated in a multicenter study

    NARCIS (Netherlands)

    Willems, P; Verhagen, O; Segeren, C; Veenhuizen, P; Guikema, J; Wiemer, E; Groothuis, L; Buitenweg-de Jong, T; Kok, H; Bloem, A; Bos, N; Vellenga, E; Mensink, E; Sonneveld, P; van der Schoot, HLE; Raymakers, R

    2000-01-01

    Recently the Belgium-Dutch Hematology-Oncology group initiated a multicenter study to evaluate whether myeloma patients treated with intensive chemotherapy benefit from additional peripheral stem cell transplantation. To determine treatment response accurately, we decided to quantitate malignant cel

  10. Cytogenetically unrelated clones in hematological neoplasms.

    Science.gov (United States)

    Heim, S; Mitelman, F

    1989-01-01

    We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.

  11. Clinical observation of treatment with recombinant human thrombopoietin on chemotherapy - induced thrombocytopenia in patients with hematological malignancies%重组人血小板生成素治疗恶性血液病化疗后血小板减少的临床观察

    Institute of Scientific and Technical Information of China (English)

    郝鲁梅; 马树沛

    2011-01-01

    目的 评价国产重组人血小板生成素(rhTPO)对恶性血液病患者化疗后血小板减少的临床疗效和安全性.方法 化疗后血小板≤20×109/L的12例白血病和淋巴瘤患者接受方案和剂量相同的2个周期化疗,第1周期作为自身对照,第2周期当血小板≤50×109/L时皮下注射rhTPO 15 000 U/d为用药组,连续用药8~14 d(血小扳升至≥75×109/L停用),监测血及尿常规、肝肾功能、凝血功能.结果 用药组血小板最低平均值(11±4)×109/L与对照组(9.4±2.9)×109/L比较,差异无统计学意义(P>0.05),血小板<20×109/L的持续天数用药组为(7.6±2.0)d,和对照组[(8.7±2.2)d]比较差异有统计学意义(P<0.05).血小板恢复最高值分别为(253±86)×109/L和(178±53)×109/L,差异有统计学意义(P<0.05).血小板输注量用药组为(21.7±3.9)U,对照组为(24.2±5.1)U,差异无统计学意义(P>0.05).用药组未见严重不良反应.结论 rhTPO可减少恶性血液病化疗后血小板降低的持续时间,提高血小板恢复后水平,且具有良好的安全性.%Objective To evaluate the safety and effectiveness of rhTPO on the treatment of chemotherapy - induced thrombocytopenia in patients with hematological malignancies. Methods Twelve leukemia and lymphoma patients with platelet count ≤20 × 109/L after chemotherapy were enrolled in the current study. They received two courses of chemotherapy with identical regimen and dosage. The first course was used as self - control. In the second course, rhTPO was subcutaneously administered at a dosage of 15 000 U/d for 8 - 14 days (until the platelet count ≥75× 109/L) when platelet count ≤50 × 109/L. Laboratory tests included blood routine and urine routine, serum biochemisty, blood coagulation tests. Results The mean minimal platelet count was( 11 ±4) × 109/L in the treatment goup versus(9.4 ±2.9) ×109/L in the control group, the difference was no significant (P >0.05). The duration of patients

  12. Malignant hyperthermia

    Science.gov (United States)

    ... you need surgery, tell both your surgeon and anesthesiologist before surgery if: You know that you or ... IN. Malignant hyperthermia and muscle-related disorders. In: Miller RD, ed. Miller's Anesthesia . 8th ed. Philadelphia, PA: ...

  13. Eosinophilia in hematologic disorders

    Science.gov (United States)

    Falchi, Lorenzo; Verstovsek, Srdan

    2015-01-01

    Synopsis A finding of eosinophilia in the peripheral blood can be the manifestation of a large number of different medical conditions, including benign or malignant disorders. From a diagnostic standpoint eosinophilia can be divided into reactive (secondary) or clonal (primary). There are three main types of WHO-defined eosinophilia-associated myeloid neoplasms (MN-eos): 1) myeloid and lymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB or FGFR1; 2) chronic eosinophilic leukemia, not otherwise specified (CEL-NOS); and 3) idiopathic hypereosinophilic syndrome (HES). Imatinib mesylate, a PDGFRA and PDGFRB inhibitor, has revolutionized the treatment of molecularly defined MN-eos. Second generation molecules are available for patients who fail imatinib. Novel agents, such as the anti-IL5 antibody mepolizumab, have been successfully used for the treatment of HES. The discovery of new, recurrent molecular alterations in patients with MN-eos may improve the diagnosis and therapy of this group of patients. This review focuses on the hematologist’s approach to a patient with eosinophilia as well as treatment options for patients with eosinophilic myeloid neoplasms. PMID:26209894

  14. RHI Refractories Opens Dalian Plant

    Institute of Scientific and Technical Information of China (English)

    Stefan Pirker

    2004-01-01

    @@ End of November the opening ceremony of the RHI Refractories Dalian plant took place in the presence of 250 guests from China and Europe. RHI Refractories welcomed highly official guests from the Dalian City and the Dalian Development Area, the Supervisory Board of RHI, the company's biggest shareholder, the Board of Management, representatives of customers in China as well as Professors of China's refractory academic field. The ceremony' s highlight was the speech of Professor Zhong Xiangchong from Zhengzhou University, member of the China Academy of Science, who pointed out RHI Refractories' long and successful history of refractory innovations during the last decades and the future possibilities of collaboration with RHI Refractories.

  15. Progress on the diagnosis and treatment of refractory leukemia%难治性白血病诊治进展

    Institute of Scientific and Technical Information of China (English)

    王季石; 卢英豪

    2009-01-01

    It is difficult for the patients of refractory leukemia to complete remission (CR) and long-term disease-free survival (DFS), and it was always been the hot spots of research in the field of hematologic malignancies. The diagnostic criteria of refractory leukemia were adjusted constantly at domestic and foreign, the high-risk factors about refractory leukemia were found constantly too. New molecular markers that represent mutations or gene overexpression have been identified such as FMS-like tyrosine kinase-3 and nucleophosmin,which will enhance the ability to more accurately prognosticate for patients with acute myeloid leukemia. The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Multiple new agents with tremendous potential were in development and clinical trials. Such as applying resistance reversal agents,enhancing molecular targeted therapy, improving the technology of hematopoietic stem cell transplantation,empoldering the new drugs, and forming a new chemotherapy program etc. Monoclonal antibodies and peptide vaccination with leukemia-associated antigens also brought the hopes of increasing the remission and cure rates for patients with acute myeloid leukemia.%难治性白血病因其本身特性难达完全缓解和长期无病生存,始终是恶性血液病领域研究的热点和难点,国内外关于难治性白血病的诊断标准在不断调整,引起白血病难治高危的因素也在不断的被发现;新的分子标志,基因突变或某些基因高表达,如FLT3跨膜区内部串联重复等,这些分子标志将决定急性白血病患者的预后.治疗难治性或复发性急性髓细胞性白血病仍然具有挑战性.多种新药正在开发和临床试验.临床许多新的治疗方法正在探讨.如应用耐药逆转剂、加强分子靶向治疗、改进造血干细胞移植和开发新药、组成新的化疗方案等;单克隆抗体和多肽疫苗与白血病相关抗原为治愈急性白血病带来了希望.

  16. 42 CFR 493.941 - Hematology (including routine hematology and coagulation).

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Hematology (including routine hematology and coagulation). 493.941 Section 493.941 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency...

  17. Hematological disorders and pulmonary hypertension

    Science.gov (United States)

    Mathew, Rajamma; Huang, Jing; Wu, Joseph M; Fallon, John T; Gewitz, Michael H

    2016-01-01

    Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH. PMID:28070238

  18. FLT3/ITD基因突变在不同血液肿瘤患者的表达及其临床意义%Detection of FLT3/ITD gene mutations in patients with hematologic malignancy and their clinical Significance

    Institute of Scientific and Technical Information of China (English)

    Bing Xu; Guoshu Chen; Xiaodan Luo; Jiahong Tang

    2009-01-01

    Objective:To analyze Fms-like tyrosine kinase 3(FLT3)/intemal-tandem duplications(ITD)murations in various kinds of hematologic malignancy patients.Methods:FLT3/ITD gene mutations were detected by polymerase chain reaction (PCR)in 103 acute myeloid leukemia(AML)cases,63 acute lymphocytic leukemia(ALL)cases,53 chronic myelogenous leukemia(CML)cases in chronic phase(CML-CP),34 CML cases in biast crisis(CML-BC),11 chronic lymphatic leukemia(CLL)cases,36 myelodysplastic syndrome (MDS)cases,9 multiple myeloma(MM)cases and 13 non-hodgkin's lymphoma (NHL)cases with marrow infiltration.Results:The expressions of FLT3/ITD gene mutations were detected in 22.3% AML cases.in 6.5%CML-BC cases.in 5.6%MDS cases and in 2.6%ALL cases.The two ALL cases with FLT3/ITD mutation were diagnosed as ALL-L2 with morphology and both with myeloid antigen expression,but finally were diagnosed as acute mixed-lineage leukemia after immunology examination.FLT3/ITD gene muIations were not detected in CML-CP,MM.NHL and CLL cases.In the 23 AML patients with FLT3/ITD gene mutation,including 2 of 8 M1(2.5%),8 of 33 M2(24-2%),7 of 24 M3(29.3%),2 of 11 M4(18.2%).3 of 21 M5(14.3%),1 of 5 M6(20%),and 0 of 1 M7 cases,and there were no significant differences in the positive rates of FLT3/ITD mutations between the FAB subtypes(P>0.05).Statistical analyses showed that in AML patients,FLT3/ITD was associated with a higher pefipheral blood white cell(WBC)counts[(41.23±32.56)x 100/L vs (11.36±9.89)x109/L(P<0.01)],higher percentage of bone marrow blast cells[(72.78±21.79)%vs(51.26±20.78)%(P<0.05)],and higher cumulative relapse rates(63.6%vs 27.7%,P<0.025)than those negative.Conclusion:FLT3/ITD gene mutation mainly pccurred in AML patients.and might be a strong prognostic factor which was associated with high peripheral WBC counts.bone marrow blast cell proportion and a increased relapse risk in AML.Detection of FLT3/ITD gene mutation might provide insights to explore a more accurate genotyping of

  19. Refractory peptic ulcer disease.

    Science.gov (United States)

    Napolitano, Lena

    2009-06-01

    Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.

  20. Idelalisib therapy of indolent B-cell malignancies: chronic lymphocytic leukemia and small lymphocytic or follicular lymphomas

    Directory of Open Access Journals (Sweden)

    Madanat YF

    2016-03-01

    Full Text Available Yazan F Madanat,1 Mitchell R Smith,2 Alexandru Almasan,3 Brian T Hill2 1Department of Internal Medicine, 2Department of Hematology and Medical Oncology, Taussig Cancer Institute, 3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma are indolent B-cell lymphoproliferative disorders that mainly affect an older population. Although the majority of patients in need of treatment derive significant benefit from conventional chemotherapeutic agents as well as monoclonal antibodies, less toxic and more effective treatments are needed. Novel agents that inhibit the B-cell receptor signaling pathway have shown promising outcomes in these disorders. Idelalisib is a potent selective oral inhibitor of phosphatidylinositol 3-kinase delta and has shown significant clinical activity in B-cell malignancies. In this review, we summarize the clinical trial data using idelalisib as monotherapy or in combination with rituximab for the treatment of relapsed/refractory disease. The adverse effect profile includes autoimmune disorders such as transaminitis, colitis, and pneumonitis. Given the efficacy and manageable toxicity profile of idelalisib, it is being increasingly incorporated into the management of indolent B-cell malignancies. Keywords: idelalisib, PI3Kδ inhibitors, chronic lymphocytic leukemia, follicular lymphoma

  1. Malignant Catatonia

    Directory of Open Access Journals (Sweden)

    Ayca Ozkul

    2010-12-01

    Full Text Available Catatonia is a syndrome characterized by mutism, immobility, negativism, stereotypy, mannerisms, echophenomena, perseveration and passive obedience. The underlying causes can be psychiatric or may be associated with general medical status or neurological diseases. Additionally catatonia has two subtypes as malignant and nonmalignant catatonia. Main symptoms of malignant catatonia are hyperthermia and autonomic symptoms such as tachycardia, tachypnea and hyperhidrosis. It is important to make the diagnosis as early as possible for an appropriate medical treatment. Clinicians should be aware of the fatal outcome of the disease.

  2. Malignant hyperthermia

    Directory of Open Access Journals (Sweden)

    Michael P Phy

    2016-01-01

    Full Text Available Malignant hyperthermia is a rare metabolic crisis triggered by volatile anesthetics and/or succinylcholine. It is important to remember that hyperthermia is not always present and may even present late in the course. Early recognition of the most common signs and symptoms is critical to diagnosis and treatment. Malignant hyperthermia was associated with a high mortality rate, but this has decreased with the use of dantrolene.  Although this is frequently reported in the anesthesia and surgical literature, it is important that critical care units that use succinylcholine as part of their intubation sequence be prepared to identify and treat this serious syndrome.

  3. Malignant glaucoma

    Directory of Open Access Journals (Sweden)

    Sebastião Cronemberger

    2012-10-01

    Full Text Available The aim of this review is to discuss current knowledge about pathophysiology and clinical, therapeutic and prophylactic approaches for malignant glaucoma. This type of glaucoma can occur after different surgical procedures. It can also occur in aphakic, phakic and pseudophakic eyes and develop spontaneously in individuals with no ocular surgical history, or associated with topical miotics. Currently, the ultrasound biomicroscopy has provided many interesting and useful findings for diagnosis and monitoring the treatment of malignant glaucoma. It occurs more often in short eyes in which pre operative measurements of the anterior chamber depth and axial length are extremely important for its prophylaxis and diagnosis.

  4. Dynamic Testing of Gasifier Refractory

    Energy Technology Data Exchange (ETDEWEB)

    Michael D. Mann; Wayne S. Seames; Devdutt Shukla; Xi Hong; John P. Hurley

    2005-12-01

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by refractory materials under slagging coal gasification conditions. The goal of this work is to devise a mechanism of refractory loss under these conditions. The controlled-atmospheric dynamic corrodent application furnace (CADCAF) was utilized to simulate refractory/slag interactions under dynamic conditions that more realistically simulate the environment in a slagging coal gasifier than any of the static tests used previously by refractory manufacturers and researchers. High-alumina and high-chromia refractory bricks were tested using slags obtained from two solid fuel gasifiers. Testing was performed at 1475 C in a reducing atmosphere (2% H{sub 2} in N{sub 2}) The CADCAF tests show that high-chrome refractories have greater corrosion resistance than high-aluminum refractories; coal slag readily diffuses into the refractory through its grain boundaries; the refractory grains are more stable than the matrix in the tests, and the grains are the first line of defense against corrosion; calcium and alkali in the slag are more corrosive than iron; and silicon and calcium penetrate the deepest into the refractory. The results obtained from this study are preliminary and should be combined with result from other research programs. In particular, the refractory corrosion results from this study should be compared with refractories removed from commercial gasifiers.

  5. Refractory Minerals in Henan Province

    Institute of Scientific and Technical Information of China (English)

    JIN Qinguo; LI Jing; LIU Jiehua; LIU Yanjun

    2004-01-01

    Henan province is very rich in refractory minerals of many varieties including silica, dolomite, graphite,pearlite, sepiolite, olivine, and sillimanite group minerals, besides the abundant reserves of fireclay and bauxite,which lay a good foundation for the development of the refractories industry of the province. The paper introduces the reserves, distribution and character of the refractory minerals in Henan province.

  6. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation.

    Science.gov (United States)

    Kanagal-Shamanna, Rashmi; Loghavi, Sanam; DiNardo, Courtney D; Medeiros, L Jeffrey; Garcia-Manero, Guillermo; Jabbour, Elias; Routbort, Mark J; Luthra, Rajyalakshmi; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2017-06-28

    A subset of patients with familial platelet disorder with propensity to myeloid malignancy and germline RUNX1 mutation develops hematological malignancies, often myelodysplastic syndrome/acute myeloid leukemia, currently recognized in the 2016 WHO classification. Patients who develop hematologic malignancies are typically young, respond poorly to conventional therapy, and need allogeneic stem cell transplant from non-familial donors. Understanding the spectrum of bone marrow morphologic and genetic findings in these patients is critical to ensure diagnostic accuracy and develop criteria to recognize the onset of hematologic malignancies, particularly myelodysplastic syndrome. However, bone marrow features remain poorly characterized. To address this knowledge gap, we analyzed the clinicopathologic and genetic findings of 11 patients from 7 pedigrees. Of these, 6 patients did not develop hematologic malignancies over a 22-month follow-up period; 5 patients developed hematologic malignancies (3 acute myeloid leukemia; 2 myelodysplastic syndrome). All patients had thrombocytopenia at initial presentation. All 6 patients who did not develop hematologic malignancies showed baseline bone marrow abnormalities: low-for-age cellularity (n=4), dysmegakaryopoiesis (n=5), megakaryocytic hypoplasia/hyperplasia (n=5), and eosinophilia (n=4). Two patients had multiple immunophenotypic alterations in CD34-positive myeloblasts; 1 patient had clonal hematopoiesis. In contrast, patients who developed hematologic malignancies had additional cytopenia(s) (n=4), abnormal platelet granulation (n=5), bone marrow hypercellularity (n=4), dysplasia in ≥2 lineages including megakaryocytes (n=3) and acquired clonal genetic aberrations (n=5). In conclusion, our study demonstrated that specific bone marrow abnormalities and acquired genetic alterations may be harbingers of progression to hematological malignancies in patients with familial platelet disorder with germline RUNX1 mutation

  7. MUCORMYCOSIS IN HEMATOLOGIC PATIENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    García-Romero Maria Teresa

    2011-01-01

    Full Text Available Most invasive fungal infections occur in patients with hematologic malignancies and the prevalence has increased steadily in recent years due to intensive cytotoxic chemotherapies, stem cell transplantation, myeloablative radiation therapy, and the use of corticosteroids, cyclosporine or new immunosuppressive agents. Although Candida is the main fungal agent involved in invasive fungal infection (IFI, an increasing number of infections are caused by molds, mostly Aspergillus spp, but in the last 20 years other emerging fungal pathogens such as Zygomycetes causing mucormycosis have appeared with higher mortality rates. The rhinocerebral and pulmonary forms of mucormycosis together with disseminated disease have the highest mortality (78-100%. Zygomycetes characteristically invade blood vessels, causing thrombosis and infarction with necrosis and scarring. Rapid diagnosis of zygomycosis is vital for management and therapy since these infections progress rapidly. Treatment should combine early aggressive surgical excision of the necrotic lesions, restoration of immune function if possible, and amphotericin B at a dose of 1-1.5 mg/kg or a new antifungal such as posaconazole.

  8. End of life care in hematology: still a challenging concern.

    Science.gov (United States)

    Niscola, Pasquale; Tendas, Andrea; Scaramucci, Laura; Giovannini, Marco

    2014-01-01

    The majority of patients with hematological malignancies (HM) may experience troublesome symptoms and complicating clinical syndromes throughout all phases of disease. Therefore, among the current concepts concerning the comprehensive management of hematological patients, palliative care should exert a more ever expanding role, in particular in the advanced phases of disease, as there are special clinical needs (such as blood transfusions and anti-infective treatments), presented by this peculiar category of cancer patients. However, reported experiences on advanced HM patients claimed a too intensive level of medical care during the last week of life for which the needs of future and collaborative researches in order to set a proper allocation of medical resources and the optimal end-of-life care in the hematologic setting are highly awaited. Indeed, the most important aspect of caring for these suffering patients is to ameliorate or restore their quality of life (QoL) though a highly humanized approach, whereas technological and pharmacological measures should be limited enough to control the symptoms burden and the several kinds of sufferance that may complicate the final phase of disease course.

  9. Status epilepticus: Refractory and super-refractory.

    Science.gov (United States)

    Dubey, Deepanshu; Kalita, Jayantee; Misra, Usha K

    2017-01-01

    Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

  10. Extracorporeal life support for refractory ventricular tachycardia

    Science.gov (United States)

    Joseph, Nicholas; Hofmann, James P.; Saranteas, Theodosios; Papadimos, Thomas J.

    2017-01-01

    Extracorporeal life support (ECLS) is a very effective bridging therapy in patients with refractory ventricular tachycardia (VT) associated with cardiogenic shock. A moribund patient in extremis, is not amenable to optimization by standard ACC/AHA guidelines. New approaches and novel salvage techniques are necessary to improve outcomes in patients with refractory clinical settings such as malignant ventricular arrhythmias, cardiac arrest, cardiogenic shock and/or pulmonary failure until further management options are explored. Data base searches were done using key words such as ECLS, VT, cardiac arrest, VT ablation, venoarterial extra-corporeal membrane oxygenation (VA-ECMO). The use of ECLS has been described in a few case reports to facilitate VT ablation for incessant VT refractory to medical therapy. For patients with, out-of- hospital ventricular fibrillation (VF) and VT, Minnesota Resuscitation Consortium has implemented emergent advanced perfusion and reperfusion strategy, followed by coronary angiography and primary coronary intervention to improve outcome. The major indications for ECLS are cardiogenic shock related to acute myocardial infarction, myocarditis, post embolic acute cor pulmonale, drug intoxication and post cardiac arrest syndrome with the threat of multi-organ failure. ECLS permits the use of negative inotropic antiarrhythmic drug therapy, facilitates the weaning of catecholamine administration, thereby ending the vicious cycle of catecholamine driven electric storm. ECLS provides hemodynamic support during ablation procedure, while mapping and induction of VT is undertaken. ECLS provides early access to cardiac catheterization laboratory in patients with cardiac arrest due to shockable rhythm. The current evidence from literature, supports the use of ECLS to ensure adequate vital organ perfusion in patients with refractory VT. ECLS is a safe, feasible and effective therapeutic option when conventional therapies are insufficient to support

  11. Cyto diagnosis and cytomorphologic analysis of hematolymphoid malignancy in serous effusion:a study of 23 cases

    Institute of Scientific and Technical Information of China (English)

    何淑蓉

    2012-01-01

    Objective To evaluate the value of cytomorphologic and immunocytochemical approaches in the diagnosis of hematologic neoplasms in serious effusion. Methods The cytospin and Thinprep smears of effusion specimens were prepared from 23 cases of lymphoid malignancies with histological

  12. Refractory headache: classification and nomenclature.

    Science.gov (United States)

    Levin, Morris

    2008-06-01

    There are a number of reasons to attempt to define and classify refractory headache disorders. Particularly important are the potential benefits in the areas of research, treatment, and medical cost reimbursement. There are challenges in attempting to classify refractory forms of headaches, including the lack of biological or other objective markers and a lack of consensus among practitioners as to what qualifies as refractoriness, or even if a separate category for refractory migraine and other refractory headaches needs to be established. A definition of refractory migraine has been proposed by Schulman et al in this issue ("Defining Refractory Migraine [RM] and Refractory Chronic Migraine [RCM]: Proposed Criteria for the Refractory Headache Special Interests Section of the American Headache Society"), which should be tested for validity and usefulness. It seems reasonable to consider adding this defined syndrome to the International Classification of Headache Disorders, second edition (ICHD-II). In this article, options for adding refractory headache syndromes to the ICHD are discussed with pros and cons for each. Two "best" options for adding the disorder "refractory migraine" to the ICHD are presented along with an illustrative case example.

  13. Zygomycosis in Two Hematologic Cases

    Directory of Open Access Journals (Sweden)

    M. T. García-Romero

    2011-01-01

    Full Text Available Zygomycosis are invasive mould infections, rarely diagnosed in hematologic patients. Most of the cases published are in patients with prolonged neutropenia, along with other risk factors such as the use of prior broad-spectrum antibiotics (including new antifungal agents, such as voriconazole, diabetes mellitus (with or without ketoacidosis, malnutrition, iron overload (with or without the use of deferoxamine. These infections have poor prognosis due to the involvement of vital anatomic structures and late diagnosis. Until recent years, the treatment was based on high doses of amphotericin B plus surgical debridement. Here we present two patients with hematologic diseases (one with leukemia, the second with aplastic anemia with an impaired immune system and the diagnosis of zygomycosis. The survival of one of them was mainly due to early diagnosis and surgical debridement; unfortunately the second was misdiagnosed as an extensive ecchymosis due to thrombocytopenia and died with CNS involvement.

  14. Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies.

    Science.gov (United States)

    Oshima, Kumi; Kanda, Yoshinobu; Nakahara, Fumio; Shoda, Eriko; Suzuki, Takahiro; Imai, Yoichi; Watanabe, Takuro; Asai, Takashi; Izutsu, Koji; Ogawa, Seishi; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2006-11-01

    We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 micro g/ml, the peak alemtuzumab concentration in this patient was only 1.44 micro g/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation.

  15. Breast cancer as second malignant neoplasm after acute myeloid leukemia: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Govind Babu

    2016-01-01

    Full Text Available Cancer survivors after successful treatment of hematological and lymphoid malignancies are at an increased risk for second malignant neoplasms. As the overall survival has increased in these cancers, solid tumors are emerging as a serious long-term complication. In this article, we describe such a rare occurrence, in literature, of breast cancer after the treatment of acute myeloid leukemia.

  16. In Vitro Leukoagglutination: A Rare Hematological Cause of Spurious Leukopenia

    Directory of Open Access Journals (Sweden)

    Sadia Sultan

    2017-08-01

    Full Text Available Leukopenia secondary to leukocytic agglutination is caused by an ethylene diamine tetra acetic acid (EDTA which may appear in both benign and malignant states. Ethylene diamine tetra acetic acid induced platelets clumping in peripheral blood has been well established, but invitro leukocytic aggregation is very rarest hematological finding. Pseudo-leukopenia resulting from leukoagglutinins has been reported in the cirrhotic state, infections, autoimmune disorders, uremia, in immunosuppressed state or in various malignancies. Though the condition seems to be benign but very important to be detected as these artifactual findings lead to unnecessary investigations and remarkably changed the overall management plan. Here we report the case of a young patient with this rare finding who was admitted to our hospital with progressive labor pains. The analysis of ethylene diaminetetraacetic acid (EDTA, anticoagulated blood was done on automated hematology analyzer reveals leukopenia. The peripheral smear examination revealed multiple aggregates of leukocytes. On repeat sampling in citrate anticoagulant, the complete blood count showed total leukocytic count of 16.5x109/L with absolute neutrophilic count of 11.5x109/L. This is a rare case of spurious leukopenia secondary to in-vitro leukocytic agglutination provoked by EDTA anticoagulant.

  17. Advances and prospect of hematology

    Directory of Open Access Journals (Sweden)

    Jian-min WANG

    2011-03-01

    Full Text Available Over the past decade,promising progress has been made in hematology by domestic and oversea researchers,such as the biological features of hematopoietic stem cells,underlying mechanism involving epigenetics of hematological disease and the intervention measures thereof,molecular diagnosis and targeted therapy,optimization of therapeutic protocol for hematopoietic stem cell transplantation,selection of alternative donors,and prevention and treatment of complications post transplantation.Development of hematology in the future will focus on the following fields.Chromosome translocation and gene mutation are key diagnostic criteria in the new version of WHO classification of tumors of hematopoietic and lymphoid tissues.And the detections of these aberrant alterations make tailored therapy and follow-up of therapeutic effects possible.And more attention should be placed on the translational research of stem cell and niche,as well the pathogenesis of hematopoietic diseases including aberrant histone acetylation,DNA methylation and expression of abnormal micro RNA,which will promote the further understanding of the pathogenesis of hematopoietic diseases and made targeted therapy as well as personalized medicine possible.In addition,the prevention and treatment of complications of stem cell transplantation are made through the optimization of conditioning regimen,the combination of different drugs as well as cellular immunization,which should greatly improve the effects of hematopoietic stem cell transplantation,and bring benefits to the patients and can be utilized in the medical rescue in military events.

  18. TET proteins and 5-methylcytosine oxidation in hematological cancers.

    Science.gov (United States)

    Ko, Myunggon; An, Jungeun; Pastor, William A; Koralov, Sergei B; Rajewsky, Klaus; Rao, Anjana

    2015-01-01

    DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting, and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of ten-eleven-translocation (TET) family dioxygenases that oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies.

  19. A "bone marrow score" for predicting hematological disease in immunocompetent patients with fevers of unknown origin.

    Science.gov (United States)

    Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Yang, Sheng-Hsiang; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Chun-Yu; Liu, Jin-Hwang; Chen, Po-Min; Hsu, Hui-Chi; Fung, Chang-Phone; Tzeng, Cheng-Hwai; Hsiao, Liang-Tsai

    2014-12-01

    Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, "bone marrow (BM) score", to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease. Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort. For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively. As immunocompetent FUO patients with hematological disease have poor prognoses, the "BM score" is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.

  20. Refractory gastroesophageal reflux disease

    OpenAIRE

    Joaquim Prado P. Moraes-Filho

    2012-01-01

    CONTEXT: Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Its pathophysiology, diagnosis and treatment have frequently been analyzed but it is interesting to review some aspects of the GERD refractory patients to the proton pump inhibitors treatment. The treatment encompasses behavioral measures and pharmacological therapy. The majority of the patients respond well to proton pump inhibito...

  1. Colectomy for refractory constipation

    DEFF Research Database (Denmark)

    Raahave, Dennis; Loud, Franck Bjørn; Christensen, Elsebeth;

    2010-01-01

    OBJECTIVE: This study evaluated the type of colectomy, postoperative complications, functional results, and satisfaction in patients with constipation refractory to conservative therapy. Further, colonic transit time (CTT), faecal load (coprostasis), and colon length (redundancies) were compared...... had at hemicolectomy, 11 patients a subtotal colectomy and 3 patients an ileostomy. Two patients had an anastomotic leak and one died. In 11 patients, further surgery was necessary, because of recurrent constipation. Abdominal pain disappeared and defecation patterns improved significantly to 1-4 per...

  2. Refractory status epilepticus

    Directory of Open Access Journals (Sweden)

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  3. Clinical Observation on the Changes of Serum Immune Parameter in Patients with Hematological Malignancies Transfused with Irradiation Aphaeresis Platelet%输注辐照血小板后血液病患者免疫参数变化的临床观察

    Institute of Scientific and Technical Information of China (English)

    张一琼; 杨晨敏

    2012-01-01

    count primary reference material for traceability. Methods The uncertainty of the primary was prepared by stabilizing the blood cells, adjusting the concentration and subpackaging the blood. The reference material was evaluated according to ISO Guide 35 and "Technical Norm of Primary Reference Material", including homogeneity study, stability study and characterization by the standard analyzer which can be traceable to reference method directly. The uncertainty from homogeneity, stability, and characterization were evaluated. The combined uncertainty and extended uncertainty were calculated. The uncertainty between the primary reference material and the secondary reference material were compared. Results The results of one-way analysis of variance of WBC, RBCHb and PLT showed that the reference material was homogeneous (JP>0. 05). The between-bottle homogeneity uncertainty (u bb) of the above parameters were 0. 04 × 109/L, 0. 022 × 1012/L, 0. 1 g/L and 2. 2 × 109/L respectively. The reference material was stable in 26 weeks by trend analysis (P>0. 05). The stability uncertainty (ults.) of the above parameters were 0. 08×10VL, 0. 023×1012/L, 1. 1 g/L and 3. 6×109/L respectively. The characterization uncertainty (uchar) of the above parameters were 0. 09×10VL, 0. 059 × 1012/L, 1. 2 g/L and 4. 1×10VL respectively. After calculating the combined uncertainty and extended uncertainty, the assigned values were (5. 4±0. 3) × 109/L, (4. 42±0. 13) × 1012/L, (137±3)g/L and (187±12) × 109/L respectively. The primary reference material is smaller than that of the secondary reference material. Conclusion The candidate reference material had preferable homogeneity and stability, and the method of characterization of the candidates is accurate and reliable. The uncertainty of all parameters of the primary reference material is smaller than that of the secondary reference material.Objective Research on the changes of serum immune parameter in patients with hematological

  4. Pediatric and adult patients (aged from 1 to 70 years) with hematologic malignancies (leukemia, myeloma, lymphoma), candidates for allogeneic transplantation from HLA-identical or HLA-mismatched family is from the register. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available patologie maligne ematologiche (leucemia, mieloma, linfoma), candidati a trapianto allogenico da donatore H...rogressive è definita come aumento del 25% della maggior parte dei parametri di malattia (blastica della leucemia

  5. The European Hematology Association Roadmap for European Hematology Research : a consensus document

    NARCIS (Netherlands)

    Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

    2016-01-01

    The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology rese

  6. The European Hematology Association Roadmap for European Hematology Research : a consensus document

    NARCIS (Netherlands)

    Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

    2016-01-01

    The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology rese

  7. Refractories Utilizability for Slagging Gasifiers

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Slagging coal gasification process became a highlight of coal chemical industry in China during the last decade. Refractory lining's life of slagging gasifiers is one of the most critical factors for a cost -effective operation. The paper introduces current status of coal gasification in China, lining structure of slagging gasifiers and performance of refractory lining. It also summarizes the major factors impacting on refractory wear in slagging coal gasifiers in four Chinese chemical plants, based on ten years of industrial experience. The utilizability is discussed in terms of cost -effectiveness of high chromia refractories and possibility of the alternatives.

  8. Primary or secondary antifungal prophylaxis in patients with hematological maligancies: efficacy and damage

    Directory of Open Access Journals (Sweden)

    Gedik H

    2014-04-01

    Full Text Available Habip Gedik,1 Funda Şimşek,1 Taner Yildirmak,1 Arzu Kantürk,1 Deniz Arica,2 Demet Aydin,2 Naciye Demirel,2 Osman Yokuş21Department of Infectious Diseases and Clinical Microbiology, 2Department of Hematology, Ministry of Health Okmeydani Training and Research Hospital, İstanbul, TurkeyBackground: Patients with hematological malignancies often develop febrile neutropenia (FN as a complication of cancer chemotherapy. Primary or secondary antifungal prophylaxis is recommended for patients with hematological malignancies to reduce the risk of invasive fungal infection (IFI. This study retrospectively evaluated the efficacy and potential harm of administration of primary and secondary antifungal prophylaxis to patients with hematological malignancies at one hospital.Methods: All patients with hematological malignancies older than 14 years of age who had experienced at least one FN attack during chemotherapy while being treated at one hospital between November 2010 and November 2012 were retrospectively evaluated.Results: A total of 282 FN episodes in 126 consecutive patients were examined during a 2-year study period. The mean patient age was 51.73±14.4 years (range: 17–82 years, and 66 patients were male. Primary prophylaxis with posaconazole was administered to 13 patients and systemic antifungal treatment under induction or consolidation chemotherapy to seven patients. Of 26 patients who received secondary antifungal prophylaxis with either oral voriconazole (n=17 or posaconazole (n=6 during 46 FN episodes, systemic antifungal therapy was administered in 16 of 38 episodes and three of eight episodes, respectively. Secondary antifungal prophylaxis with caspofungin was found effective in treating six FN episodes in three patients who had experienced at least two persistent candidemia attacks. The mortality rates associated with IFI were 9% in the first year, 2% in the second year, and 6% overall. The mortality rates associated with candidemia

  9. Orind Refractories Limited

    Institute of Scientific and Technical Information of China (English)

    Mr R. Mishra; Group Manging Director

    2005-01-01

    @@ "Sight can be acquired, Vision cannot". Orind Refractories Limited (ORIND), China was formed with this rare vision. At a time when the world was testing the tepid waters of China; Mr. Ravin Jhunjhunwala, Chairman of ORIND and the management of ORIND India had looked over the Great Wall to begin a journey of success. Incorported on 18th August 1994 with an initial investment of USD 5 million, ORL caters to the ever-demanding needs of the steel industry and beyond. Incidentally ORIND was the first wholly owned India company to set up base in China. Pesently, ORIND China has a 616 strong work force including 23 expatriates.

  10. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...... in pharmacological management of chronic atrial fibrillation....

  11. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-cell Neoplasms

    Science.gov (United States)

    Holkova, Beata; Perkins, E. Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Shrader, Ellen; Talreja, Neha; Wellons, Martha D.; Hogan, Kevin T.; Roodman, G. David; Coppola, Domenico; Kang, Loveleen; Dawson, Jana; Stuart, Robert K.; Peer, Cody; Figg, William D.; Kolla, Sarah; Doyle, Austin; Wright, John; Sullivan, Daniel M.; Roberts, John D.; Grant, Steven

    2011-01-01

    Purpose A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximally tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B cell malignancies (multiple myeloma, indolent and mantle cell lymphoma). Experimental Design Patients received bortezomib by IV push on days 1, 4, 8 and 11. Patients also received alvocidib on days 1 and 8 by 30 min bolus infusion followed by a 4 hour continuous infusion. Treatment was on a 21 day cycle, with indefinite continuation for patients experiencing responses or stable disease. Dose escalation employed a standard 3+3 design until the MTD was identified based upon DLTs. Pharmacokinetic studies and pharmacodynamic studies were performed. Results Sixteen patients were treated. The MTD was established as 1.3 mg/m2 for bortezomib and 30 mg/m2 for alvocidib (both the 30 min bolus and 4 hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common non-hematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate 44%). Pharmacokinetic results were typical for alvocidib, and pharmacodynamic studies yielded variable results. Conclusions The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non-Hodgkin’s lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. PMID:21447728

  12. Development of Refractories for Continuous Casting

    Institute of Scientific and Technical Information of China (English)

    TIAN Shouxin; JIN Congjin; YAO Jinfu; LI Zeya

    2004-01-01

    The paper introduces refractories for continuous casting, especially, refractories for continuous casting for clean steel in baosteel. Developing direction of refractories for continuous casting has been pointed out to satisfy the new metallurgical operating practice.

  13. Effects of aerobic exercise on hematologic indices of women with rheumatoid arthritis: A randomized clinical trial

    OpenAIRE

    2016-01-01

    Background: To investigate the effects of moderate aerobic exercise on the hemoglobin, hematocrit, and red blood cell (RBC) mass of women with rheumatoid arthritis (RA). Materials and Methods: This randomized clinical trial was conducted at the Specialized Clinic of Physical Medicine and Rehabilitation, Al-Zahra Hospital of Isfahan, during a 4-month period in 2014. We included patients with RA who did not have any malignancy and hematologic disorder. Two groups — one group receiving aerobic t...

  14. Hematology of infancy and childhood: Third edition

    Energy Technology Data Exchange (ETDEWEB)

    Nathan, D.G.; Oski, F.A.

    1987-01-01

    These two volumes consist of 14 sections, each containing several chapters. The section titles are: History, Neonatal Hematology, Bone Marrow Failure, Disorders of Erythrocyte Production, Hemolytic Anemias, Disorders of Hemoglobin, The Phagocyte System, The Immune System, Oncology, Storage Disease, Coagulation, Genetics, Transfusion Therapy, and Hematologic Manifestations of Systemic Diseases.

  15. Approaches to refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Jerome Engel

    2014-01-01

    Full Text Available Epilepsy is one of the most common serious neurological conditions, and 30 to 40% of people with epilepsy have seizures that are not controlled by medication. Patients are considered to have refractory epilepsy if disabling seizures continue despite appropriate trials of two antiseizure drugs, either alone or in combination. At this point, patients should be referred to multidisciplinary epilepsy centers that perform specialized diagnostic testing to first determine whether they are, in fact, pharmacoresistant, and then, if so, offer alternative treatments. Apparent pharmacoresistance can result from a variety of situations, including noncompliance, seizures that are not epileptic, misdiagnosis of the seizure type or epilepsy syndrome, inappropriate use of medication, and lifestyle issues. For patients who are pharmacoresistant, surgical treatment offers the best opportunity for complete freedom from seizures. Surgically remediable epilepsy syndromes have been identified, but patients with more complicated epilepsy can also benefit from surgical treatment and require more specialized evaluation, including intracranial EEG monitoring. For patients who are not surgical candidates, or who are unwilling to consider surgery, a variety of other alternative treatments can be considered, including peripheral or central neurostimulation, ketogenic diet, and complementary and alternative approaches. When such alternative treatments are not appropriate or effective, quality of life can still be greatly improved by the psychological and social support services offered by multidisciplinary epilepsy centers. A major obstacle remains the fact that only a small proportion of patients with refractory epilepsy are referred for expert evaluation and treatment.

  16. Refractory Celiac Disease

    Directory of Open Access Journals (Sweden)

    K Khatami

    2014-04-01

    Full Text Available Refractory celiac disease (RCD is when malabsorption symptoms and villous atrophy persist despite strict adherence to a gluten free diet (GFD for more than 12 months and other causes of villous atrophy have been ruled out.  RCD is considered a rare disease and almost exclusively occurs in adults. Persistent diarrhea, abdominal pain, weight loss are the most common symptoms in RCD. Also, anemia, fatigue, malaise, thromboembolic events and coexisting autoimmune disorders are frequent. Diagnosis of RCD is based on other causes of unresponsiveness to the GFD, particularly collagenous sprue, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma. Many disorders such as autoimmune enteropathy, tropical sprue, common variable immunodeficiency, and intolerance to non-gluten dietary proteins may have similar histological findings but not necessarily identical with CD and therefore should be excluded. Repeat intestinal biopsy may help to differentiate causes of non-responsive CD associated with ongoing villous atrophy (e.g., gluten contamination, small-bowel bacterial overgrowth, RCD. There are 2 subtypes of RCD according to absence (type I or presence (type II of an abnormal intraepithelial lymphocyte population. RCD type 1 usually becomes better with a combination of aggressive nutritional support, adherence to GFD, and pharmacologic therapies such as prednisone, budesonide and azathioprine. For RCD type 2, more aggressive therapeutic approach is needed since clinical response to therapies is less certain and may evolve into aggressive enteropathy associated T-cell lymphoma and the prognosis is poor.   Key words: Celiac Disease, Refractory.  

  17. Posaconazole in the management of refractory invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Stefan Langner

    2008-09-01

    Full Text Available Stefan Langner, Philipp B Staber, Peter NeumeisterDivision of Hematology, Department of Internal Medicine, Medical University of Graz, AustriaAbstract: The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodysplastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other difficult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections.Keywords: posaconazole, refractory invasive fungal infections, salvage therapy

  18. PET/CT in paediatric malignancies - An update

    Directory of Open Access Journals (Sweden)

    Subramanyam Padma

    2016-01-01

    Full Text Available 18F-fluorodeoxyglucose positron emission tomography (FDG-PET is a well-established imaging modality in adult oncological practice. Its role in childhood malignancies needs to be discussed as paediatric malignancies differ from adults in tumor subtypes and they have different tumor biology and FDG uptake patterns. This is also compounded by smaller body mass, dosimetric restrictions, and physiological factors that can affect the FDG uptake. It calls for careful planning of the PET study, preparing the child, the parents, and expertise of nuclear physicians in reporting pediatric positron emission tomography/computed tomography (PET/CT studies. In a broad perspective, FDG-PET/CT has been used in staging, assessment of therapy response, identifying metastases and as a follow-up tool in a wide variety of pediatric malignancies. This review outlines the role of PET/CT in childhood malignancies other than hematological malignancies such as lymphoma and leukemia.

  19. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer.

    Science.gov (United States)

    Feng, Kaichao; Guo, Yelei; Dai, Hanren; Wang, Yao; Li, Xiang; Jia, Hejin; Han, Weidong

    2016-05-01

    The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer (NSCLC). In this phase I clinical study (NCT01869166), patients with epidermal growth factor receptor (EGFR)-positive (>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune- related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR(+) T cells was 0.97×10(7) cells kg(-1) (interquartile range (IQR), 0.45 to 1.09×10(7) cells kg(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC.

  20. Refractory chronic migraine

    DEFF Research Database (Denmark)

    Martelletti, Paolo; Katsarava, Zaza; Lampl, Christian

    2014-01-01

    and in the uncontrolled application of therapeutic techniques not yet validated.The European Headache Federation Expert Group on rCM presents hereby the updated definition criteria for this harmful subset of headache disorders. This attempt wants to be the first impulse towards the correct identification......The debate on the clinical definition of refractory Chronic Migraine (rCM) is still far to be concluded. The importance to create a clinical framing of these rCM patients resides in the complete disability they show, in the high risk of serious adverse events from acute and preventative drugs...... of these patients, the correct application of innovative therapeutic techniques and lastly aim to be acknowledged as clinical entity in the next definitive version of the International Classification of Headache Disorders 3 (ICHD-3 beta)....

  1. Refractory status epilepticus.

    Science.gov (United States)

    Fernandez, Andres; Claassen, Jan

    2012-04-01

    Refractory status epilepticus (RSE) has a high morbidity and mortality. There are currently no definitive data to guide both the optimal choice of therapy and treatment goals. This review focuses on RSE diagnosis and outcome and discusses both commonly used and anecdotal therapies for RSE. The challenges in performing randomized controlled trials (RCTs) in neurocritical care and more specifically for the treatment of RSE are illustrated by the early termination of the first RCT of RSE due to low recruitment that compared propofol to barbiturates. Recent case series include the successful treatment of recurrent RSE with ketamine, intravenous lacosamide as an add-on treatment, the use of combination antiepileptics (phenytoin, levetiracetam, and pregabalin), and surgical treatments (vagal nerve and deep brain stimulation) for the control of RSE. A number of different therapeutic options are available for the treatment of RSE but none have been shown to be superior to others at this point.

  2. Refractory chronic cluster headache

    DEFF Research Database (Denmark)

    Mitsikostas, Dimos D; Edvinsson, Lars; Jensen, Rigmor H

    2014-01-01

    Chronic cluster headache (CCH) often resists to prophylactic pharmaceutical treatments resulting in patients' life damage. In this rare but pragmatic situation escalation to invasive management is needed but framing criteria are lacking. We aimed to reach a consensus for refractory CCH definition...... for clinical and research use. The preparation of the final consensus followed three stages. Internal between authors, a larger between all European Headache Federation members and finally an international one among all investigators that have published clinical studies on cluster headache the last five years....... Eighty-five investigators reached by email. Proposed criteria were in the format of the International Classification of Headache Disorders III-beta (description, criteria, notes, comments and references). Following this evaluation eight drafts were prepared before the final. Twenty-four (28...

  3. Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer.

    Directory of Open Access Journals (Sweden)

    Ursula M Schick

    Full Text Available Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS. The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE and the Women's Health Initiative (WHI. We detected clonal mosaicism in 169 individuals (1.4% and large clonal mosaic events (>2 mb in 117 (1.0% individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia, the carriers had a 5.5-fold increased risk (95% CI: 3.3-9.3; p-value = 7.5×10(-11 of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value = 7.3×10(-14. Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.

  4. Confirmation of the Reported Association of Clonal Chromosomal Mosaicism with an Increased Risk of Incident Hematologic Cancer

    Science.gov (United States)

    Crane, Paul K.; Weston, Noah; Ehrlich, Kelly; Newton, Katherine M.; Wallace, Robert; Bookman, Ebony; Harrison, Tabitha; Aragaki, Aaron; Crosslin, David R.; Wang, Sophia S.; Reiner, Alex P.; Jackson, Rebecca D.; Peters, Ulrike; Larson, Eric B.; Jarvik, Gail P.; Carlson, Christopher S.

    2013-01-01

    Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women’s Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3–9.3; p-value = 7.5×10−11) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9–41.6; p-value = 7.3×10−14). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications. PMID:23533652

  5. 单次大剂量足叶乙甙联合G-CSF用于恶性血液病患者自体外周血造血干细胞动员的临床研究%Clinical study on high-dose etoposide with granulocyte colony-stimulating factor for mobilization of autologous peripheral blood stem cells in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    沈文怡; 吴汉新; 李建勇; 洪鸣; 张闰; 陆化; 刘澎; 钱思轩; 徐卫; 仇红霞

    2012-01-01

    目的 探讨单次大剂量足叶乙甙(Vp16)静脉注射联合粒细胞集落刺激因子(G-CSF)用于恶性血液病患者自体外周血造血干细胞(APBSC)动员的有效性和安全性.方法 80例恶性血液病患者包括急性白血病(AL)20例、多发性骨髓瘤(MM)23例、非霍奇金淋巴瘤(NHL)35例、霍奇金淋巴瘤(HL)2例,均采用Vp16 1.6 g /m2匀速持续静脉注射10 h,外周血中性粒细胞计数(ANC)降至1×109/L时开始给予G-CSF 10 μg·kg-1·d-1皮下注射,至采集结束.WBC>5.0×109/L时开始APBSC采集,目标值:单个核细胞(MNC)≥6.0×108/kg且CD34+细胞≥2.0×106/kg.患者经预处理后回输自体外周血干细胞.观察动员采集过程中血液学指标变化、采集细胞数量、造血重建时间、不良反应等.结果 足叶乙甙应用后11(7~25) d开始干细胞采集,中位采集次数为2(1~5)次.80例患者中,APBSC动员失败3例,均为急性非淋巴细胞白血病(ANLL)患者;既往其他方案动员自体干细胞失败的6例患者中5例动员成功,1例既往阿糖胞苷动员失败的ANLL-M5患者足叶乙甙动员仍失败;77例患者CD34+细胞中位数为4(1.59~24.68)×106/kg,其中3例患者CD34+细胞未达2×106/kg,但移植后造血顺利重建.对20例AL和23例MM患者采集物行微量残留病检测,未发现采集物残留肿瘤细胞污染.所有患者均良好耐受动员、采集过程.80例患者在干细胞动员过程中,Ⅳ度白细胞减少发生率为36.25%(29/80),感染发生率为23.75%(19/80).结论 单次大剂量足叶乙甙联合G-CSF动员APBSC总体成功率高,不良反应可控,是恶性血液病患者动员采集APBSC安全有效的方案.%Objective To explore the effectivity and safety of single high-dose(HD) etoposide(Vp16) with granulocyte colony-stimulating factor(G-CSF) for mobilization of autologous peripheral blood stem cells(PBSC) in patients with hematologic malignancies. Methods 80 patients of hematologic malignancies including 20 patients

  6. Two cases of malignant glaucoma unresolved by pars plana vitrectomy

    Directory of Open Access Journals (Sweden)

    Hosoda Y

    2014-04-01

    Full Text Available Yoshikatsu Hosoda, Tadamichi Akagi, Nagahisa YoshimuraDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, JapanAbstract: Malignant glaucoma, which is characterized by a shallow or flat anterior chamber with high intraocular pressure, can usually be resolved by pars plana vitrectomy with anterior hyaloidectomy. We describe two cases in which malignant glaucoma was refractory to conventional treatment and complete vitrectomy. Case one an 88-year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and subsequently developed malignant glaucoma. Four months after transient recovery by pars plana vitrectomy, the malignant glaucoma recurred. She underwent peripheral iridectomy and local zonulectomy with successful control of her intraocular pressure. In case two, an 85-year-old man had a history of pseudoexfoliation glaucoma. Seven months after phacoemulsification and intraocular lens implantation, he developed malignant glaucoma that was refractory to pars plana vitrectomy. He underwent peripheral iridectomy, goniosynechialysis and trabectome surgery resulting in the successful control of his intraocular pressure. In rare cases of malignant glaucoma refractive to vitrectomy, peripheral iridectomy with or without local zonulectomy is a reasonable and minimally invasive surgical procedure.Keywords: malignant glaucoma, pars plana vitrectomy, peripheral iridectomy

  7. Sample Preparation for Monolithic Refractories Part 1: Refractory Castables

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiaohui; Peng Xigao

    2010-01-01

    @@ 1 Scope This standard specifies the definition and test methods of flowability of dense and insulating refractory castables,and moulding equipment,moulding methods,curing and drying conditions of castables samples.

  8. Invasive fungal diseases in children with hematologic disorders

    Directory of Open Access Journals (Sweden)

    Ünsal Günay

    2009-12-01

    Full Text Available Objective: Fungal infection is a significant problem, causing of infective deaths of leukemic patients. The situation in developing countries is not well documented. The purpose of this study was characterizing IFD by analyzing data retrospectively to determine the incidence, predisposing factors, diagnostic methods, efficacy of treatment, and the outcome in pediatric patients with hematological disorders. Materials and Methods: There were 160 children with leukemia (22 AML, 129 ALL and 9 with aplastic anemia (AA. The diagnostic criteria for IFD were defined according to the EORTC/MSG, 2008. IFD was classified as proven or probable. Empiric antifungal treatment with L-AmB was commenced by day 5-7 of persistent fever. Patients with invasive aspergillosis (IA who were refractory to primary treatment were commenced on voriconazole (VCZ. Salvage therapy as combination of VCZ and caspofungin was given to those with progressive infection. Results: The incidence of IFD was found 23 (14.3%. 19 with leukemia (14 ALL, 5 AML and 4 with aplastic anemia were diagnosed as IFD. IA was the dominant cause of infection (n=17 and the rest (n: 6 had candidiasis. Ten children had “proven” infection and 13 children were defined as “probable”. The most frequent site of infection was lungs. In our series, the most frequently used diagnostic methods were clinical findings (100% and radiologic methods (84%. The success rate of treatment for candidiasis and IA were found 60%, 71% respectively. IFD related death rate was found 30%.Conclusion: IFD is still a major morbidity and mortality reason in children with hematologic disorders. However, the availability of new antifungal treatments and diagnostic tests will improve the survival rates in these children.

  9. Evaluation and management of patients with refractory ascites

    Institute of Scientific and Technical Information of China (English)

    Bahaa Eldeen Senousy; Peter V Draganov

    2009-01-01

    Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis,malignancy or infection and non-compliance with medications and low sodium diet have been excluded,the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis (LVP) and transjugular intrahepatic portasystemic stent-shunt (TIPS) are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morbidity and mortality (most surgical options) rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.

  10. Present Situation of Refractories for Baosteel

    Institute of Scientific and Technical Information of China (English)

    TAI Li; SHEN Keyin

    2004-01-01

    The paper reviews the present situation of refractories for Baosteel, including refractories for iron-making system, converters, ladles and tundishes. Descriptions have been also conducted on the environment protection and reutilization of refractories in Baosteel, together with somesuggestions for refractories suppliers to meet the advancement in iron and steel making technology of Baosteel.

  11. Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Chapa-Rodríguez, Adrián; Rodríguez-Martínez, Marisol; Colunga-Pedraza, Perla Rocío; Marfil-Rivera, Luis Javier; Gómez-Almaguer, David

    2012-01-01

    Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms.

  12. Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Chapa-Rodríguez, Adrián; Rodríguez-Martínez, Marisol; Colunga-Pedraza, Perla Rocío; Marfil-Rivera, Luis Javier; Gómez-Almaguer, David

    2012-01-01

    Background Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. Objective The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. Methods An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. Results One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. Conclusion No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms. PMID:23049401

  13. Malignant hyperthermia

    Directory of Open Access Journals (Sweden)

    Pollock Neil

    2007-04-01

    Full Text Available Abstract Malignant hyperthermia (MH is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with

  14. Self-flow Refractory Castables

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiaohui; Peng Xigao

    2010-01-01

    @@ 1 Scope This standard specifies the term and definition,classification, technical requirements, test methods,quality appraisal procedures, packing, marking, transportation, storage, and quality certificate of self-flow refractory castables.

  15. Alumina-magnesia Refractory Castables

    Institute of Scientific and Technical Information of China (English)

    Wang Jing

    2010-01-01

    @@ 1 Scope This standard specifies the classification,technical requirements,test methods,quality appraisal procedures,packing,marking,transportation,storage,and quality certificate of alumina-magnesia refractory castables.

  16. Evaluation of the Hematological, Hypoglycemic, Hypolipidemic and ...

    African Journals Online (AJOL)

    The effect of the leaf extract on serum glucose and triglyceride, total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), elevated high density lipoprotein (HDL), body weight and hematological ... Article Metrics.

  17. Thermal effects on bluegill hematology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Murray, S.A.

    1983-03-01

    Temperature effects on hematological responses of adult bluegill were examined for constant vs fluctuating temperature regimes, for ambient vs high temperature, and for intake vs discharge at an operating power plant. Multivariate statistical methods were used to determine temperature effects. An increased erythrocyte fragility was associated with fluctuating temperature regimes as well as with the suboptimal temperature regime. Thrombocytosis with a concomitant leukopenia was observed for the higher fluctuating and higher acclimating temperatures. Reduced erythrocytic sedimentation rates were observed for the higher temperatures. Although hematology may vary depending on fish size, good hematological indicators of potential thermal stress were associated with red blood cell morphology, particularly cell size and/or shape. However, in situ hematological responses of bluegill at an operating power plant were apparently not affected by the associated thermal gradients.

  18. Interactive Hematology and Digital Learning Online

    OpenAIRE

    Rønning, Morten

    2004-01-01

    In the fall of 2001, the University of Oslo decided to prioritize the usage of digital learning systems, and offered funds for their development. We decided to use the opportunity to create a web-based, interactive learning system (1), covering basic physiological and clinical hematology. During initial development, the project was expanded to a general Content-Management System (2) for creating web-based information sites, while maintaining focus on hematology. Method The system was d...

  19. Epistaxis in Visceral Leishmaniasis with Hematological Correlation

    OpenAIRE

    Sigdel, B.; Bhandary, S.; Rijal, S

    2012-01-01

    Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Result...

  20. Hematologic responses to hypobaric hyperoxia.

    Science.gov (United States)

    Larkin, E. C.; Adams, J. D.; Williams, W. T.; Duncan, D. M.

    1972-01-01

    Study of the effects of hypoxia, activity, and G forces on human hematopoiesis in an attempt to elucidate these phenomena more precisely. Eight subjects were exposed to an atmosphere of 100% O2 at 258 mm Hg for 30 days, and thereafter immediately exposed to transverse G forces, simulating the Gemini flights' reentry profile. All subjects displayed a significant continuous decline in red cell mass during the exposure period, as measured by the carbon monoxide-dilution method. The Cr51 method also indicated a decline in red blood corpuscle mass. The decrease in red cell mass was due to suppression of erythropoiesis and to hemolysis. After exposure to hyperoxia, all subjects exhibited elevated plasma hemoglobin levels, decreased reticulocyte counts, and decreased red cell survivals. CO production rates and urine erythropoietin levels were unchanged. Two hours after termination of exposure to hyperoxia, all subjects exhibited increased reticulocyte counts which were sustained for longer than two weeks. The progressive decrease in red cell mass was promptly arrested on return to ground level atmospheres. Within 116 days after exposure to hyperoxia, the hematologic parameters of all eight subjects had returned to control levels.

  1. Comparison of Curative Efficacy after G-CSF-mobilized Sibling HLA-matched Peripheral Blood Hematopoietic Stem Cell Transplantation Versus that Combined with BMT for Patients with Hematologic Malignancies in a Single Center%同胞HLA相合供体外周血造血干细胞移植与其联合骨髓移植治疗恶性血液病疗效的单中心比较分析

    Institute of Scientific and Technical Information of China (English)

    任富鹏; 刘会兰; 孙自敏; 耿良权; 王兴兵; 丁凯阳

    2011-01-01

    本研究回顾性分析并比较了粒细胞集落刺激因子(G-CSF)动员的同胞HLA相合(sibling matched,sm)异基因外周血造血干细胞移植(sm-allo-PBHSCT)及sm-allo-PBHSCT联合骨髓移植(BMT)治疗恶性血液病的临床疗效.本中心自2001年10月至2010年10月有100例恶性血液病患者接收移植,其中sm-allo-PBHSCT组38例,sm-allo-PBHSCT+BMT组62例,根据病人情况选择清髓性及减低强度的预处理方案.所有患者均采用环孢素A(CsA)联合霉酚酸酯(MMF)方案预防移植物抗宿主病(GVHD).结果表明,两组造血重建快,中性粒细胞绝对值(ANC)≥0.5×109/L的中位时间均为12天,血小板数≥20×109/L的中位时间分别为15天(sm-allo-PBH-SCT)和16天(sm-allo-PBHSCT+BMT).两组急性GVHD、Ⅲ-Ⅳ度急性GVHD、慢性GVHD发生率分别为37.1%和34.2%、7.89%和8.06%、36.11%和41.38%,差异无统计学意义.两组复发率分别为13.16%和12.90%,3年的无病生存率分别为57.1%和61.3%.高危患者2年总生存率(OS)分别为(41.4±12.8)%和(60.9±9.6)%(p=0.017).结论:G-CSF动员的sm-allo-PBHSCT+BMT与sm-allo-PBHSCT治疗恶性血液病一样安全有效,对于高危患者可能更有利.%This study was aimed to retrospectively analyze and compare the clinical curative efficacy of patients with hematologic malignancies after G-CSF-mobilized sibling HLA-matched (sm) peripheral blood hematopoietic stem cell transplantation (sm-allo-PBHSCT) and sm-allo-PBHSCT combined with bone marrow transplantation (BMT). 100 patients received sm-allo-HSCT in a single center from October 2001 to October to 2010, included 38 patients received sm-allo-PBHSCT and 62 patients received sm-allo-PBHSCT combined with BMT. The myeloablative or reduced intensity conditioning regimens were chosen according to the condition of patients. All patients received standard cyclosporine (CsA) and mycophenolate mofetil (MMF) as prophylaxis for GVHD. The results showed that the rapid hematopoietic reconstitution was

  2. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques

    2013-01-01

    Ovarian tissue cryopreservation and transplantation is a real option to preserve and restore fertility in young cancer patients. However, there is a concern regarding the possible presence of malignant cells in the ovarian tissue, which could lead to recurrence of the primary disease after...... reimplantation. A review of the existing literature was done to evaluate the risk of transplanting malignant cells in case of the main malignant indications for ovarian tissue cryopreservation. For ovarian tissue from patients with hematologic malignancies, it is of paramount importance to identify minimal...... residual disease before ovarian tissue transplantation. Indeed, these pathologies, reviewed here in detail, are considered to be most at risk of ovarian metastasis....

  3. Impact of alternate fuels on industrial refractories and refractory insulation applications. An Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Wei, G.C.; Tennery, V.J.

    1976-09-01

    The effects of use of alternate fuels such as distillate oils, residual oils, coal, producer gas, and electricity on refractory insulation are evaluated. Sections are included on alternate fuels for 1976 to 1980, assessment by industry of fuel conversion impact on industrial refractories in the period 1976 to 1980, interactions of alternate fuel combustion products with refractories and refractory insulation, and analysis of degradation mechanisms in refractories and refractory materials. (JRD)

  4. Seronegative and occult hepatitis C virus infections in patients with hematological disorders.

    Science.gov (United States)

    Helaly, Ghada Fahmy; Elsheredy, Amel Gaber; El Basset Mousa, Adel Abd; Ahmed, Hayat Khalifa Fadlalla; Oluyemi, Abd El-Gaffar Sabry

    2017-01-01

    Studies of the association between seronegative or occult (OCI) hepatitis C virus (HCV) infection, and hematological disorders have yielded controversial results. The aim of this study was to investigate seronegative and OCI HCV infections in among patients with different hematological disorders. This study included 90 anti-HCV-negative patients with either benign or malignant hematological disorders (group I), along with 20 age- and sex-matched apparently healthy subjects, who served as controls (group II). We tested for HCV RNA in sera and PBMCs by RT-nested PCR and for liver enzyme activity. Seronegativity and OCI were detected in 66.7 % and 20 % respectively, of the studied cases (group I). OCI was more evident in Hodgkin lymphoma and thalassemia. A significant increase in AST activity was observed in the seronegative and OCI groups and in ALT and AST in HCV-seronegative or OCI and negative HCV patients (p ≤ 0.05). Seronegativity and OCI are a significant clinical problem in patients with hematological disorders, warranting wider use of molecular tests combined with periodic evaluations of liver functions for diagnostic purposes.

  5. Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole.

    Science.gov (United States)

    Gerber, Bernhard; Guggenberger, Roman; Fasler, David; Nair, Gayathri; Manz, Markus G; Stussi, Georg; Schanz, Urs

    2012-09-20

    We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment.

  6. Radiation Effects in Refractory Alloys

    Science.gov (United States)

    Zinkle, Steven J.; Wiffen, F. W.

    2004-02-01

    In order to achieve the required low reactor mass per unit electrical power for space reactors, refractory alloys are essential due to their high operating temperature capability that in turn enables high thermal conversion efficiencies. One of the key issues associated with refractory alloys is their performance in a neutron irradiation environment. The available radiation effects data are reviewed for alloys based on Mo, W, Re, Nb and Ta. The largest database is associated with Mo alloys, whereas Re, W and Ta alloys have the least available information. Particular attention is focused on Nb-1Zr, which is a proposed cladding and structural material for the reactor in the Jupiter Icy Moons Orbiter (JIMO) project. All of the refractory alloys exhibit qualitatively similar temperature-dependent behavior. At low temperatures up to ~0.3TM, where TM is the melting temperature, the dominant effect of radiation is to produce pronounced radiation hardening and concomitant loss of ductility. The radiation hardening also causes a dramatic decrease in the fracture toughness of the refractory alloys. These low temperature radiation effects occur at relatively low damage levels of ~0.1 displacement per atom, dpa (~2×1024 n/m2, E>0.1 MeV). As a consequence, operation at low temperatures in the presence of neutron irradiation must be avoided for all refractory alloys. At intermediate temperatures (0.3 to 0.6 TM), void swelling and irradiation creep are the dominant effects of irradiation. The amount of volumetric swelling associated with void formation in refractory alloys is generally within engineering design limits (>10 dpa). Very little experimental data exist on irradiation creep of refractory alloys, but data for other body centered cubic alloys suggest that the irradiation creep will produce negligible deformation for near-term space reactor applications.

  7. The european hematology association roadmap for european hematology research: A consensus document

    NARCIS (Netherlands)

    A. Engert (Andreas); C.L. Balduini (Carlo); A. Brand (Anneke); B. Coiffier (B.); C. Cordonnier (Charlotte); H. Döhner (Hartmut); De Wit, T.D. (Thom Duyvené); Eichinger, S. (Sabine); W.E. Fibbe (Willem); Green, T. (Tony); De Haas, F. (Fleur); A. Iolascon (Achille); T. Jaffredo (Thierry); Rodeghiero, F. (Francesco); Sall Es, G. (Gilles); J.J. Schuringa; J.-L. André (Jean-Luc); I. André-Schmutz (Isabelle); A. Bacigalupo; P-Y. Bochud (Pierre-Yves); M.L. den Boer (Monique); C. Bonini (Chiara); C. Camaschella (Clara); A. Cant (Andrew); M.D. Cappellini (Maria); M. Cazzola; Celso, C.L. (Cristina Lo); M.A. Dimopoulos (Meletios); Douay, L. (Luc); E.A. Dzierzak (Elaine); H. Einsele (Hermann); A.J.M. Ferreri (Andrés J.M.); De Franceschi, L. (Lucia); Gaulard, P. (Philippe); B. Göttgens (Berthold); A. Greinacher (Andreas); P. Gresele (Paolo); J. Gribben (John); De Haan, G. (Gerald); Hansen, J.-B. (John-Bjarne); A. Hochhaus (Andreas); Kadir, R. (Rezan); S.V. Kaveri (Srini); Kouskoff, V. (Valerie); Kühne, T. (Thomas); Kyrle, P. (Paul); P. Ljungman; Maschmeyer, G. (Georg); S. Mendez-Ferrer (S.); Milsom, M. (Michael); Mummery, C. (Christine); G.J. Ossenkoppele (Gert); A. Pecci (Alessandro); F. Peyvandi (Flora); J.N.J. Philipsen (Sjaak); P.H. Reitsma; J.M. Ribera (Josep Maria); Risitano, A. (Antonio); Rivella, S. (Stefano); W. Ruf (Wolfram); Schroeder, T. (Timm); Scully, M. (Marie); G. Socie (Gerard); F.J.T. Staal (Frank); S. Stanworth (Simon); Stauder, R. (Reinhard); S. Stilgenbauer (S.); Tamary, H. (Hannah); K. Theilgaard-Mönch (K.); Thein, S.L. (Swee Lay); H. Tilly (Herve); M. Trneny (Marek); Vainchenker, W. (William); A.M. Vannucchi (Alessandro); Viscoli, C. (Claudio); Vrielink, H. (Hans); Zaaijer, H. (Hans); Zanella, A. (Alberto); Zolla, L. (Lello); J.J. Zwaginga (Jaap); Martinez, P.A. (Patricia Aguilar); E. van den Akker (Eric); Allard, S. (Shubha); N.P. Anagnou (Nicholas); Andolfo, I. (Immacolata); Andrau, J.-C. (Jean-Christophe); Angelucci, E. (Emanuele); D.J. Anstee (David J.); Aurer, I. (Igor); H. Avet-Loiseau (Hervé); Y. Aydinok (Yesim); Bakchoul, T. (Tamam); Balduini, A. (Alessandra); Barcellini, W. (Wilma); Baruch, D. (Dominique); Baruchel, A. (André); J. Bayry (Jagadeesh); Bento, C. (Celeste); A. van den Berg (Anemone); Bernardi, R. (Rosa); Bianchi, P. (Paola); A. Bigas (Anna); A. Biondi (Andrea); Bohonek, M. (Milos); Bonnet, D. (Dominique); Borchmann, P. (Peter); Borregaard, N. (Niels); Brækkan, S. (Sigrid); M.R.M. Van Den Brink (Marcel R. M.); Brodin, E. (Ellen); L. Bullinger (Lars); C. Buske (Christian); Butzeck, B. (Barbara); J. Cammenga (Jörg); G. Campo (Gianluca); I. Carbone; Cervantes, F. (Francisco); S. Cesaro; P. Charbord (Pierre); F.H.J. Claas (Frans); Cohen, H. (Hannah); Conard, J. (Jacqueline); Coppo, P. (Paul); Vives Corron, J.-L. (Joan-Lluis); Da Costa, L. (Lydie); Davi, F. (Frederic); H.R. Delwel (Ruud); Dianzani, I. (Irma); Domanović, D. (Dragoslav); Donnelly, P. (Peter); Drnovšek, T.D. (Tadeja Dovč); M. Dreyling (Martin); Du, M.-Q. (Ming-Qing); Dufour, C. (Carlo); C. Durand (Charles); Efremov, D. (Dimitar); A. Eleftheriou (Androulla); Elion, J. (Jacques); M. Emonts (Marieke); M. Engelhardt (Monika); Ezine, S. (Sophie); J.H.F. Falkenburg (Frederik); Favier, R. (Remi); M. Federico (M.); P. Fenaux (Pierre); J. Fitzgibbon (Jude); Flygare, J. (Johan); R. Foà; L. Forrester (Lesley); Galacteros, F. (Frederic); Garagiola, I. (Isabella); C. Gardiner (Chris); Garraud, O. (Olivier); Van Geet, C. (Christel); H. Geiger (Hartmut); J. Geissler (Jan); U. Germing (Ulrich); Ghevaert, C. (Cedric); D. Girelli (Domenico); Godeau, B. (Bertrand); Gökbuget, N. (Nicola); H. Goldschmidt (Hartmut); A.C. Goodeve; T. Graf (Thomas); Graziadei, G. (Giovanna); Griesshammer, M. (Martin); Gruel, Y. (Yves); F. Guilhot (François); Von Gunten, S. (Stephan); I.C. Gyssens (Inge); J.P. Halter (Joerg P.); C.N. Harrison (Claire N.); C.L. Harteveld (Cornelis); Hellström-Lindberg, E. (Eva); Hermine, O. (Olivier); Higgs, D. (Douglas); Hillmen, P. (Peter); Hirsch, H. (Hans); Hoskin, P. (Peter); G. Huls (Gerwin); Inati, A. (Adlette); Johnson, P. (Peter); Kattamis, A. (Antonis); Kiefel, V. (Volker); M. Kleanthous (Marina); Klump, H. (Hannes); Krause, D. (Daniela); Hovinga, J.K. (Johanna Kremer); Lacaud, G. (Georges); Lacroix-Desmazes, S. (Sébastien); Landman-Parker, J. (Judith); Legouill, S. (Steven); Lenz, G. (Georg); M. Von Lilienfeld-Toal (Marie); M.M. von Lindern (Marieke); Lopez-Guillermo, A. (Armando); Lopriore, E. (Enrico); Lozano, M. (Miguel); E. Macintyre; M. Makris (M.); Mannhalter, C. (Christine); J.H.A. Martens (Joost); S. Mathas (Stephan); Matzdorff, A. (Axel); A. Medvinsky (Alexander); Menendez, P. (Pablo); G. Migliaccio (Giovanni); Miharada, K. (Kenichi); Mikulska, M. (Malgorzata); V. Minard (Véronique); Montalbán, C. (Carlos); De Montalembert, M. (Mariane); E. Montserrat (Emili); P.-E. Morange (P.); Mountford, J. (Joanne); Muckenthaler, M. (Martina); C. Müller-Tidow (Carsten); Mumford, A. (Andrew); B. Nadel (Bertrand); Navarro, J.-T. (Jose-Tomas); El Nemer, W. (Wassim); Noizat-Pirenne, F. (France); O’Mahony, B. (Brian); J. Oldenburg (Johannes); Olsson, M. (Martin); R.A. Oostendorp (Robert); A. Palumbo (Antonio); F. Passamonti (Francesco); R. Patient (Roger); De Latour, R.P. (Regis Peffault); F. Pflumio (Françoise); Pierelli, L. (Luca); Piga, A. (Antonio); Pollard, D. (Debra); M.H.G.P. Raaijmakers (Marc H.G.P.); J. Radford (John); Rambach, R. (Ralf); Koneti Rao, A.; Raslova, H. (Hana); Rebulla, P. (Paolo); Rees, D. (David); V. Ribrag (Vincent); A.W. Rijneveld (Anita); Rinalducci, S. (Sara); T. Robak (Tadeusz); Roberts, I. (Irene); Rodrigues, C. (Charlene); F.R. Rosendaal (Frits); Rosenwald, A. (Andreas); Rule, S. (Simon); R. Russo (Roberta); Saglio, G. (Guiseppe); Sanchez, M. (Mayka); Scharf, R.E. (Rüdiger E.); Schlenke, P. (Peter); Semple, J. (John); J. Sierra (Jorge); So-Osman, C. (Cynthia); Soria, J.M. (José Manuel); K. Stamatopoulos (K.); Stegmayr, B. (Bernd); H. Stunnenberg (Henk); D.W. Swinkels (Dorine); Barata, J.P.T. (João Pedro Taborda); T. Taghon (Tom); Taher, A. (Ali); E. Terpos (Evangelos); Thachil, J. (Jecko); Tissot, J.D. (Jean Daniel); I.P. Touw (Ivo); Toye, A. (Ash); Trappe, R. (Ralf); Traverse-Glehen, A. (Alexandra); Unal, S. (Sule); S. Vaulont (Sophie); V. Viprakasit (Vip); Vitolo, U. (Umberto); R. van Wijk (Richard); Wójtowicz, A. (Agnieszka); S. Zeerleder (Sacha); B. Zieger (Barbara)

    2016-01-01

    textabstractThe European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hem

  8. The european hematology association roadmap for european hematology research : A consensus document

    NARCIS (Netherlands)

    A. Engert (Andreas); C.L. Balduini (Carlo); A. Brand (Anneke); B. Coiffier (Bertrand); C. Cordonnier (Charlotte); H. Döhner (Hartmut); De Wit, T.D. (Thom Duyvené); Eichinger, S. (Sabine); W.E. Fibbe (Willem); Green, T. (Tony); De Haas, F. (Fleur); A. Iolascon (Achille); T. Jaffredo (Thierry); F. Rodeghiero (Francesco); G. Salles (Gilles); J.J. Schuringa (Jan Jacob)

    2016-01-01

    textabstractThe European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hem

  9. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study

    Science.gov (United States)

    Bernard, Frederic; van Noesel, Max; Barkaoui, Mohamed; Bardet, Odile; Mura, Rosella; Arico, Maurizio; Piguet, Christophe; Gandemer, Virginie; Armari Alla, Corinne; Clausen, Niels; Jeziorski, Eric; Lambilliote, Anne; Weitzman, Sheila; Henter, Jan Inge; Van Den Bos, Cor

    2015-01-01

    An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ–positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses of Ara-C (1 g/m2 per day) plus cladribine (9 mg/m2 per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity. PMID:26194764

  10. ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

    Directory of Open Access Journals (Sweden)

    Ungur R

    2015-10-01

    Full Text Available Rodica Ungur,1,2 Adrian Tempescul,3 Christian Berthou,3 Cristina Bagacean,1,2 Doinel Radeanu,1 Adriana Muresan,1 Mihnea Zdrenghea1,21Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, 2Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest Teaching Hospital, Brest, FranceAbstract: Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.Keywords: cerebral lymphoma, PCNSL, refractory, relapsed, platinum

  11. Uso de olanzapina e eletroconvulsoterapia em um paciente com esquizofrenia catatônica refratária e antecedentes de síndrome neuroléptica maligna Olanzapina y ECT en un enfermo con esquizofrenia catatónica refractaria y alto riesgo de síndrome neuroléptico maligno Olanzapine and ECT combined therapy in a refractory catatonic subtype schizophrenia patient with previous neuroleptic malignant syndrome episodes

    Directory of Open Access Journals (Sweden)

    Pedro Gomes de Alvarenga

    2005-12-01

    Full Text Available Este artigo descreve a história clínica e o manejo de um paciente masculino adulto com esquizofrenia catatônica refratária a dois neurolépticos típicos (haloperidol e clorpromazina e a outro agente atípico (risperidona, e com antecedente de dois episódios de síndrome neuroléptica maligna em vigência de neurolépticos típicos. Os autores optaram pela associação de eletroconvulsoterapia (ECT e olanzapina (7,5 mg. Foram obtidos consideráveis benefícios para o paciente.Presentamos un relato clínico referente a la historia precedente y al desarrollo de un enfermo varón con esquizofrenia catatónica refractaria a los neurolépticos convencionales (clorpromazina y haloperidol y a otro agente de nueva generación (risperidona. El enfermo presentó, en dos ocasiones, síndrome neuroléptico maligno, provocado por el uso de los neurolépticos convencionales. Los autores emplearon ECT y olanzapina (7,5 mg obteniendo considerable éxito clínico.This article describes the clinical history and management of an adult male patient with refractory catatonic schizophrenia to two typically used neurolpetic medications (haloperidol and chlorpromazine and to another atypical agent (risperidone.The patient had also presented two neuroleptic malignant syndrome episodes due to typical neuroleptic agents. The authors combined ECT and olanzapine (7.5 mg as treatment, and a considerable clinical improvement was obtained.

  12. Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms

    Science.gov (United States)

    Holkova, Beata; Kmieciak, Maciej; Perkins, E. Brent; Bose, Prithviraj; Baz, Rachid C.; Roodman, G. David; Stuart, Robert K.; Ramakrishnan, Viswanathan; Wan, Wen; Peer, Cody J; Dawson, Jana; Kang, Loveleen; Honeycutt, Connie; Tombes, Mary Beth; Shrader, Ellen; Weir-Wiggins, Caryn; Wellons, Martha; Sankala, Heidi; Hogan, Kevin T.; Colevas, A. Dimitrios; Doyle, L. Austin; Figg, William D.; Coppola, Domenico; Roberts, John D.; Sullivan, Daniel; Grant, Steven

    2014-01-01

    Purpose This phase I study was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma [MM], indolent lymphoma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma). Experimental Design Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. Results A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common non-hematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. Conclusions The combination of bortezomib and alvocidib is tolerable and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory MM or indolent non-Hodgkin's lymphoma. As the non-hybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. PMID:25248382

  13. Effect of electroconvulsive therapy on hematological parameters.

    Science.gov (United States)

    Chaturvedi, S; Chadda, R K; Rusia, U; Jain, N

    2001-11-30

    Although a complete blood count is part of the evaluation before the use of electroconvulsive therapy (ECT), there are no known hematological contraindications for the procedure. A preliminary study was done on 31 randomly selected psychiatric patients (chronic schizophrenia, n=10; acute depression, n=8; acute mania, n=6; acute psychosis, n=6; delusional disorder, n=1) receiving ECT to study its hematological effects. Blood samples were drawn just before and 0, 1 and 2 h after ECT. Hemoglobin (Hb%), total and differential leukocyte count (TLC and DLC), red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and platelet count were measured on a fully automated hematology analyzer (Sysmex K-1000). Significant changes were found in TLC, percentage of polymorphs and lymphocytes, and Hb%. Changes in other parameters were not statistically significant. More such studies are needed to substantiate these observations and to understand the mechanism and implication of these effects.

  14. HEMATOLOGIC FINDINGS IN OPERATING ROOM STAFFS

    Directory of Open Access Journals (Sweden)

    H SOLTANI

    2000-03-01

    Full Text Available Introduction. Long term exposure to trace amounts of anesthetic vapors and gases may produce hematologic and hepatic disorders in human. Since operating room (OR staffs are exposed to these agents, we decided to study their hematopoietic and hepatic systems in comparison with ordinary ward staffs. Methods. Seventy staffs from OR were compared with a matched similar number of ward staffs about their hematologic and hepatic laboratory findings in a historical cohort study. Findings. Mean of leukocyte and platelet counts were significantly lower in OR staffs, but in normal range. Mean of monocyte count was significantly higher in OR staffs. No significant differences were found between two groups for other hepatic and hematologic tests. Fatigue and headache were reported in OR staffs more than others. Conclusion. These findings may warn a risk to OR staffs but, it is not clear and requires further controlled studies.

  15. Company Profile Dengfeng Chunsheng Refractories Co., Ltd.

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Dengfeng Chunsheng Refractories Co., Ltd. is an industrial enterprise integrating refractories research, design, manufacturing and engineering service into one and was entitled as one of China's high-quality silica bricks production and export bases.

  16. SINTERED REFRACTORY TUNGSTEN ALLOYS. Gesinterte hochschmelzende wolframlegierungen

    Energy Technology Data Exchange (ETDEWEB)

    Kieffer, R.; Sedlatschek, K.; Braun, H.

    1971-12-15

    Dependence of the melting point of the refractory metals on their positions in the periodic system - alloys of tungsten with other refractory metals - sintering of the alloys - processing of the alloys - technological properties.

  17. [Malignant soft tissue tumors].

    Science.gov (United States)

    Schauer, A; Altmannsberger, M

    1984-01-01

    This article is a survey of actual aspects. With regard to frequency, the malignant fibrous histocytoma comes first, followed by lipo- and fibrosarcoma, synovial sarcoma, malignant schwannoma, malignant tumours proceeding from arteries and veins and the unstriated musculature. Staging and grading of these tumours are difficult. Until now their overall TNM-classification was not possible due to insufficient hard criteria.

  18. Interferon-γ-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines

    OpenAIRE

    2014-01-01

    Background Despite encouraging results with the proteasome inhibitor bortezomib in the treatment of hematologic malignancies, emergence of resistance can limit its efficacy, hence calling for novel strategies to overcome bortezomib-resistance. We previously showed that bortezomib-resistant human leukemia cell lines expressed significantly lower levels of immunoproteasome at the expense of constitutive proteasomes, which harbored point mutations in exon 2 of the PSMB5 gene encoding the β5 subu...

  19. Magnesia-Chrome Refractories for Flash Furnace

    Institute of Scientific and Technical Information of China (English)

    LI Yong; CHEN Kaixian; LU Xinghua; LIU Jianlong; SUN Jialin; HONG Yanruo

    2002-01-01

    The rapid development of our country's heavy nonferrous metallurgical technology and the revolution in new type of heavynon-ferrous metallurgical furnace have imposed more critical demand on the refractory materials ,i. e. high quality and long service life. This paper presents the domestic status of the refractories for flash furnace , briefly describes the wear of the refractory used , and it is considered that the domestic in refractories for flashfurnace can be surely realized.

  20. Reuse and Reproduction of Used Refractories

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The paper analyzed the recycle condition and developing trend of used refractories China and other countries, including research achievements of recycles of used refractories such as MgO-C bricks, Al2O3-MgO-C bricks, Al2O3-SiC-C castable and MgO-Cr2O3 bricks. Recycled refractories exhibit the same or even better properties as compared with the original. In addition, prospects for recycle of used refractories are also discusseded.

  1. Obinutuzumab for relapsed or refractory indolent non-Hodgkin's lymphomas.

    Science.gov (United States)

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

    The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin's lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc-Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma.

  2. Distinct inflammatory mediator patterns characterize infectious and sterile systemic inflammation in febrile neutropenic hematology patients.

    Directory of Open Access Journals (Sweden)

    Christine Wennerås

    Full Text Available BACKGROUND: Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. METHODS: In this prospective study, febrile (>38°C neutropenic patients (n = 42 with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures, a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10 as infected or non-infected was tested. RESULTS: A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. CONCLUSIONS: It is possible to separate patients with infectious inflammation from those

  3. Management of chronic refractory cough.

    Science.gov (United States)

    Gibson, Peter G; Vertigan, Anne E

    2015-12-14

    Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.

  4. Refractory disease in autoimmune diseases

    NARCIS (Netherlands)

    Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda

    2011-01-01

    Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It c

  5. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

  6. 全血细胞分析仪与外周血涂片对检测恶性血液病患者白细胞分类结果的比较%Comparison of blood cell analyzer and peripheral blood smear on the white cell classification results in patients with malignant hematological diseases

    Institute of Scientific and Technical Information of China (English)

    陈小君; 孟淑娟

    2015-01-01

    Objective To reduce the error of white blood cell classification , compensate the cell morphology identification ability, and improve the accuracy of peripheral white blood cell classification of the blood cell analyzer. Methods Samples of 75 patients with hematological diseases were collected from the Tangshan Iron and Steel Hospital. After anticoagulated by EDTA-K2, samples were used for the detection of CBC+diff using the Sysmex XT-1800i whole blood five classification system , at the same time abnormal white blood cell classification specimen prepared two pieces of two blood smears were prepared from the same sample and stained with Wright-Giemsa staining and counted for different types of white blood cells such as neutrophils, lymphocytes and monocytes. Results By the comparison of determination of blood smear and blood cell counting instrument, differences mainly display in the counting of lymphocytes and monocytes by blood smear method and the blood counting instrument were significantly different (47.35±18.14)vs(38.40±17.60);(6.80±2.12)vs(12.68±1.40)(t=12.650, P<0.05;t=15.200,P<0.05). Conclusion The discrepancy generated in the blood counting instrument might be due to the chromosome abnormalities in the patients white blood cells , resulting in the over estimate of monocytes and under estimate of lymphocytes, therefore compensate by blood smear examination is important.%目的:降低血细胞分析仪对血液病患者白细胞分类计数的出错率,弥补血细胞分析仪对细胞形态识别能力的不足,提高外周白细胞分类的准确性。方法收集唐钢医院75例血液病患者标本,经EDTA-K2抗凝采用Sysmex XT-1800i全血五分类血细胞仪进行CBC+diff检测,同时对异常白细胞分类标本制备血涂片2张,经瑞氏-吉姆萨染色后在显微镜下进行白细胞分类计数,观察嗜酸性粒细胞、中性粒细胞、淋巴细胞、单核细胞等指标。结果将血涂片计数与血细胞仪

  7. Hypercalcemia of malignancy and new treatment options

    Directory of Open Access Journals (Sweden)

    Sternlicht H

    2015-12-01

    Full Text Available Hillel Sternlicht,1 Ilya G Glezerman1,2 1Division of Nephrology and Hypertension, Weill Cornell Medical College, 2Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA Abstract: Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP. Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient’s symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet. Finally, anti

  8. Hematological outcome in neonatal alloimmune hemolytic disease

    NARCIS (Netherlands)

    Rath, Mirjam Eva Aafke

    2013-01-01

    This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the

  9. Hematological outcome in neonatal alloimmune hemolytic disease

    NARCIS (Netherlands)

    Rath, Mirjam Eva Aafke

    2013-01-01

    This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the

  10. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    T. A. Мitinа

    2015-01-01

    Full Text Available 49 patients aged 28 to 81 years old (median age of 55 years old with relapsed or refractory multiple myeloma (MM were enrolled in the study. The relapse was diagnosed in 25 (51 % patients, the refractory disease was determined in 24 (49 % patients (including primary refractory disease in 14 (28.6 % patients. The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %. Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP. The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR in 1 (2 % patient; very good partial response (VGPR in 4 (8 % patients; partial response (PR in 26 (53 % patients; minimal response (MR in 2 (4 % patients; stable disease (SD in 8 (16.3 % patients, and progressive disease (PD in 8 (16.3 % patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 % patients. The objective response rate, including MR, was seen in 33 (67.1 % patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

  11. PICU血液肿瘤患儿粒细胞减少症伴脓毒性休克的临床特点与预后%Characteristics and outcomes of septic shock in onto-hematological malignancy children with granulocytopenia in the pediatric intensive care unit

    Institute of Scientific and Technical Information of China (English)

    李璧如; 王莹; 张建; 赵醴; 钱娟; 杨燕文; 任宏

    2009-01-01

    目的 探讨PICU住院的血液肿瘤患儿化疗后骨髓抑制期或再生障碍性贫血(骨髓增生低下)状态下粒细胞减少症并发脓毒性休克的临床特点及影响预后的因素.方法 对我院2002年1月至2008年5月PICU收治的40例血液肿瘤患儿粒细胞减少症并发脓毒性休克临床资料进行回顾性分析.结果 本组40例患儿,存活12例,死亡18例,放弃治疗10例,病死率60%(剔除放弃病例).在发生脓毒性休克时全部病例体温均显著升高(>38.5℃),C反应蛋白也明显升高.肺部感染是其主要病因(35%),其次为胃肠道感染(30%).本组血培养阳性结果 20例,其中革兰阴性杆菌14例(14/20,70%),铜绿假单胞菌为首位(8/14,57%).存活组与死亡组血糖、血浆白蛋白水平、血pH值、标准碱剩余、乳酸和小儿死亡危险评分比较,差异均有显著性(P38.5 ℃) when they had septic shock; C-reaction protein (CRP) was significantly elevated. The main causes were pulmonary infections (35%) ,gastrointestinal tract infections (30%). Twenty patients had positive blood culture results, among whom 14 were Gram-negative bacilli infections (14/20,70%) and pseudomonas aemginosa was the main pathogen (8/14,57%). There were significant differences in serum glucose,serum albumin level,pH,standard base excess(SBE) ,serum lactic acid level and the Pediatric Risk Index Score for Mortality Ⅲ (PRISM Ⅲ) between the survival group and the death group (P<0.05). The mortality were 41% and 85% in patients with septic shock between primary remission or secondary remission group and relapse or non-remission group, and there was significantly difference (P<0.05). For the septic shock with dysfunction of 1,2,3 ,or more organs,mortality were 0,27% ,89%, 100% (excluded the quitted cases), and there was significantly difference (P<0.05). Conclusion For granulocytopenia children who were in bone marrow inhibition phase with malignancy post-chemotherapy or had bone marrow

  12. Androgen receptor gene mutations in hormone-refractory prostate cancer.

    Science.gov (United States)

    Wallén, M J; Linja, M; Kaartinen, K; Schleutker, J; Visakorpi, T

    1999-12-01

    Prostate cancer is considered to be one of the most hormone-dependent human malignancies. As a key mediator of hormonal response, the androgen receptor (AR) is believed to have an important role in the progression of prostate cancer. Mutations in the coding region of the AR gene have been found in both untreated and hormone-refractory prostate cancer, but the frequency of such mutations at different stages of the disease is poorly documented and even contradictory results have been published. In the present study, the frequency of AR gene mutations was determined in 30 locally recurrent and two metastatic hormone-refractory prostate tumours using the polymerase chain reaction (PCR), non-radioactive single strand conformation polymorphism (SSCP), and sequencing. The length of the polymorphic CAG repeat, which is inversely correlated with the ability of the AR to activate transcription, was also analysed as well as the GGC repeat. Twelve samples were known to contain an AR gene amplification. Altogether, one point mutation (Gly(674)-->Ala) and one microsatellite mutation (CAG(20)-->CAG(18)) were found, both in cancers containing the AR gene amplification. The mean lengths of the polymorphic CAG and GGC repeats were similar to those observed in the normal population. These results favour the view that mutations in the AR gene are rare in hormone-refractory prostate cancer and do not play an important role, at least, in local relapse. Instead, the amplification and consequent overexpression of the wild-type AR gene seem to be the most common alteration involving the AR in hormone-refractory prostate cancer.

  13. Miles Technicon H.2 automated hematology analyzer.

    Science.gov (United States)

    1992-11-01

    Automated hematology analyzers are used in all large hospitals and most commercial laboratories, as well as in most smaller hospitals and laboratories, to perform complete blood counts (including white blood cell, red blood cell, and platelet counts; hemoglobin concentration; and RBC indices) and white blood cell differential counts. Our objectives in this study are to provide user guidance for selecting, purchasing, and using an automated hematology analyzer, as well as to present an overview of the technology used in an automated five-part differential unit. Specifications for additional automated units are available in ECRI's Clinical Laboratory Product Comparison System. We evaluated the Miles Technicon H.2 unit and rated it Acceptable. The information in this Single Product Evaluation is also useful for purchasing other models; our criteria will guide users in assessing components, and our findings and discussions on some aspects of automated hematology testing are common to many available systems. We caution readers not to base purchasing decisions on our rating of the Miles unit alone, but on a thorough understanding of the issues surrounding automated hematology analyzers, which can be gained only by reading this report in its entirety. The willingness of manufacturers to cooperate in our studies and the knowledge they gain through participating lead to the development of better products. Readers should refer to the Guidance Section, "Selecting and Purchasing an Automated Hematology Analyzer," where we discuss factors such as standardization, training, human factors, manufacturer support, patient population, and special features that the laboratory must consider before obtaining any automated unit; we also provide an in-depth review of cost issues, including life-cycle cost analyses, acquisition methods and costs of hardware and supplies, and we describe the Hemacost and Hemexmpt cost worksheets for use with our PresValu and PSV Manager CAHDModel software

  14. Chromia refractory brick with carbon treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, James P.; Kwong, Kyei-Sing

    2017-03-21

    The disclosure provides a refractory brick system comprising a chromia refractory brick for operation in the slagging environment of an air-cooled gasifier. The chromia refractory brick comprises a ceramically-bonded porous chromia refractory having a porosity greater than 9% and having carbon deposits residing within the pores. The brick may be further comprised of Al.sub.2O.sub.3. The air-cooled gasifier generates a liquefied slag in contact with the refractory brick and generally operates at temperatures between 1250.degree. C. and 1575.degree. C. and pressures between 300 psi to 1000 psi, with oxygen partial pressures generally between 10.sup.-4 and 10.sup.-10 atm. The refractory brick performs without substantial chromium carbide or chromium metal formation in the low oxygen partial pressure environment. The inclusion of carbon without chromium carbide formation provides for significant mitigation of slag penetration and significantly reduced refractory wear.

  15. Refractory Intracranial Hypertension due to Fentanyl Administration Following Closed Head Injury

    Directory of Open Access Journals (Sweden)

    Sara E Hocker

    2013-01-01

    Full Text Available BackgroundAlthough the effects of opioids on intracranial pressure have long been a subject of controversy, they are frequently administered to patients with severe head trauma. We present a patient with an uncommon paradoxical response to opioids.Case ReportA patient with refractory intracranial hypertension after closed head injury was managed with standard medical therapy with only transient decreases in the intracranial pressure. Only after discontinuation of opiates did the intracranial pressure become manageable without metabolic suppression and rescue osmotic therapy, implicating opiates as the etiology of refractory intracranial hypertension in this patient. ConclusionsClinicians should consider opioids as a contributing factor in malignant intracranial hypertension when findings on neuroimaging do not explain persistent and refractory intracranial hypertension.

  16. Donor Lymphocyte Infusions Used to Treat Mixed-Chimeric and High-Risk Patient Populations in the Relapsed and Nonrelapsed Settings after Allogeneic Transplantation for Hematologic Malignancies Are Associated with High Five-Year Survival if Persistent Full Donor Chimerism Is Obtained or Maintained.

    Science.gov (United States)

    Caldemeyer, Lauren E; Akard, Luke P; Edwards, John R; Tandra, Anand; Wagenknecht, Dawn R; Dugan, Michael J

    2017-07-13

    Mixed chimerism (MC), a persistent or increasing number of host cells after allogeneic hematopoietic stem cell transplantation (HSCT), is a predictor of disease relapse. Donor lymphocyte infusions (DLI) have the potential to enhance the graft-versus-malignancy (GVM) effect, reducing the risk of relapse in patients with MC. Hence, in addition to utilizing DLI in the relapsed setting, there is a motivation to pursue pre-emptive DLI for patients in complete remissions after HSCT. To assess the safety and efficacy of DLI, records of 86 patients who received DLI between 2003 and 2015 at a single institution were studied retrospectively. Patients who received DLI included 50 patients with relapsed/residual (RR) disease, 29 patients with emerging MC without detectable disease, and 7 patients in an "other" cohort who had neither RR disease nor emerging MC after HSCT. DLI were administered using a dose-escalation protocol. After DLI, 93% of MC patients converted to full donor chimerism (FDC). Nonrelapsed patients (MC and other) reported high overall survival (OS) at 1 and 5 years (83% at 1 year, 70% at 5 years for MC; 86% at 1 year, 69% at 5 years for other) and was statistically superior to 5-year OS for RR patients (nonrelapsed 69% versus RR 28%; P = .00032). Improved survival correlated with successful conversion to FDC after DLI for RR and MC cohorts: 71% 2-year OS for patients converted to FDC versus 13% for patients who failed to achieve FDC (P year progression-free survival (PFS) of 71% compared with 18% 5-year PFS in the RR group (P < .0001). Relapse/progressive disease was the most frequent cause of death (41%). Seven MC (24%), 2 other (29%), and 39 RR patients (78%) relapsed or did not respond after DLI. Overall, 6 patients (7%) died of graft-versus-host disease after DLI. Our results demonstrate a successful dose-escalation approach for nonrelapsed patients that correlated with high survival and a high rate of achieving FDC in MC and RR populations. DLI

  17. Alloimmune refractoriness to platelet transfusions.

    Science.gov (United States)

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  18. Gab Adapter Proteins as Therapeutic Targets for Hematologic Disease

    Directory of Open Access Journals (Sweden)

    Sheetal Verma

    2012-01-01

    Full Text Available The Grb-2 associated binder (Gab family of scaffolding/adaptor/docking proteins is a group of three molecules with significant roles in cytokine receptor signaling. Gabs possess structural motifs for phosphorylation-dependent receptor recruitment, Grb2 binding, and activation of downstream signaling pathways through p85 and SHP-2. In addition, Gabs participate in hematopoiesis and regulation of immune response which can be aberrantly activated in cancer and inflammation. The multifunctionality of Gab adapters might suggest that they would be too difficult to consider as candidates for “targeted” therapy. However, the one drug/one target approach is giving way to the concept of one drug/multiple target approach since few cancers are addicted to a single sig