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Sample records for acute lymphocytic leukemia

  1. Acute Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  2. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    International Nuclear Information System (INIS)

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-01-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child

  3. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; 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 Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic 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 Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  4. Campylobacter jejuni Bacteremia in a Patient With Acute Lymphocytic Leukemia

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    Anvarinejad, Mojtaba; Amin Shahidi, Maneli; Pouladfar, Gholam Reza; Dehyadegari, Mohammad Ali; Mardaneh, Jalal

    2016-01-01

    Introduction Campylobacter jejuni is a slender, motile, non-spore-forming, helical-shaped, gram-negative bacterium. It is one of the most common causes of human gastroenteritis in the world. The aim of this study was to present a patient with acute lymphocytic leukemia (ALL), who was infected with Campylobacter jejuni. Case Presentation We describe the medical records of a pediatric ALL patient with bacteremia caused by C. jejuni, who was diagnosed at Amir hospital, Shiraz, Iran. This 14-year-old male visited the emergency department of Amir hospital with night sweats, severe polar high-grade fever, reduced appetite, and nausea in August 2013. Given the suspected presence of an anaerobic or microaerophilic microorganism, aerobic and anaerobic blood cultures were performed using an automated blood cultivator, the BACTEC 9240 system. In order to characterize the isolate, diagnostic biochemical tests were used. Antibiotic susceptibility testing was done with the disk diffusion method. The primary culture was found to be positive for Campylobacter, and the subculture of the solid plate yielded a confluent growth of colonies typical for Campylobacter, which was identified as C. jejuni by morphological and biochemical tests. The isolate was resistant to ciprofloxacin, cefotaxime, cephalexin, piperacillin/tazobactam, nalidixic acid, aztreonam, cefuroxime, cefixime, ceftazidime, and tobramycin. Conclusions C. jejuni should be considered in the differential diagnosis as a potential cause of bacteremia in immunosuppressed patients. In cases where the BACTEC result is positive in aerobic conditions but the organism cannot be isolated, an anaerobic culture medium is suggested, especially in immunocompromised patients. PMID:27621914

  5. Basal ganglia calcification on CT-scanning in children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Smith, D.; Bloch, S.; Al-Rashid, R.A.

    1980-01-01

    Calcification occurring in the basal ganglia in children with acute hympocytic leukemia following therapy is uncommon and to the best of our knowledge has not been reported prior to therapy. Eleven cases of bilateral symmetrical calcification in the basal ganglia were noted in 2350 CT scans, two being in children with acute lymphocytic leukemia. In one of the two cases, calcification was present prior to therapy. (orig.)

  6. Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

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    Ito, Shoko; Fujiwara, Shin-Ichiro; Mashima, Kiyomi; Umino, Kento; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-05-01

    The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

  7. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  8. Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Siviero-Miachon, Adriana Aparecida; Spinola-Castro, Angela Maria; Lee, Maria Lúcia de Martino; Andreoni, Solange; Geloneze, Bruno; Lederman, Henrique; Guerra-Junior, Gil

    2013-01-01

    Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process

  9. Identification of TP53 as an Acute Lymphocytic Leukemia Susceptibility Gene Through Exome Sequencing

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    Powell, Bradford C.; Jiang, Lichun; Muzny, Donna M.; Treviño, Lisa R.; Dreyer, ZoAnn E.; Strong, Louise C.; Wheeler, David A.; Gibbs, Richard A.; Plon, Sharon E.

    2014-01-01

    Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes. PMID:23255406

  10. CRUSTED SCABIES IN A PATIENT WITH ACUTE LYMPHOCYTIC LEUKEMIA

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    Mamatha

    2015-06-01

    Full Text Available A 17 year s old male patient presented with diffuse, ill defined, hyperpigmented, scaly plaques on the body, for the past 15 days. Lesions were more over the groin and also on both elbows and wrists. Patient is a known case of acute lymphocytic leukaemia, diagnosed a t the age of 13 years and has been on treatment ever since. A KOH ( 10% mount of the scales showed the presence of sarcoptes scabiei and skin biopsy with haematoxylin and eosin showed fragments of mite in the excised skin.

  11. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro

    International Nuclear Information System (INIS)

    Kawasaki, E.S.; Clark, S.S.; Coyne, M.Y.; Smith, S.D.; Champlin, R.; Witte, O.N.; McCormick, F.P.

    1988-01-01

    The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, the authors have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome

  12. Method of automating of the separation of blasts and lymphocytes in the diagnosis of acute myeloid leukemia

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    Blindar, V. N.; Nikitaev, V. G.; Polyakov, E. V.; Matveeva, I. I.

    2017-01-01

    The work deals with the separation of the lymphocytes of healthy patients from blasts of patients with acute myeloblastic leukemia (different variants of the disease). In this study the evaluation of textural characteristics has been done for nuclei of blood cells for cells classification and for the determination of a variant of acute myeloblastic leukemia.

  13. MR imaging of osteonecrosis of the knee in children with acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Karimova, E.J. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Kaste, Sue C. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States)

    2007-11-15

    This essay illustrates various patterns of progression of osteonecrosis of the knee and the relationship between early MR imaging findings and radiologic outcome in children with acute lymphocytic leukemia. It also includes a review of nonosteonecrosis signal abnormalities, which are common in the knee region and are often transient. Such abnormalities must be distinguished from osteonecrosis, which can lead to joint collapse and predispose to secondary arthritis. (orig.)

  14. Detection of acute lymphocyte leukemia using k-nearest neighbor algorithm based on shape and histogram features

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    Purwanti, Endah; Calista, Evelyn

    2017-05-01

    Leukemia is a type of cancer which is caused by malignant neoplasms in leukocyte cells. Leukemia disease which can cause death quickly enough for the sufferer is a type of acute lymphocyte leukemia (ALL). In this study, we propose automatic detection of lymphocyte leukemia through classification of lymphocyte cell images obtained from peripheral blood smear single cell. There are two main objectives in this study. The first is to extract featuring cells. The second objective is to classify the lymphocyte cells into two classes, namely normal and abnormal lymphocytes. In conducting this study, we use combination of shape feature and histogram feature, and the classification algorithm is k-nearest Neighbour with k variation is 1, 3, 5, 7, 9, 11, 13, and 15. The best level of accuracy, sensitivity, and specificity in this study are 90%, 90%, and 90%, and they were obtained from combined features of area-perimeter-mean-standard deviation with k=7.

  15. Effects of central-nervous-system irradiation on neuropsychologic functioning of children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Soni, S.S.; Marten, G.W.; Pitner, S.E.; Duenas, D.A.; Powazek, M.

    1975-01-01

    Two neuropsychologic studies were performed to determine the long-term effects of ''prophylactic'' cranial or craniospinal irradiation on the psychologic and neurologic functions of children with acute lymphocytic leukemia. In a prospective study, 34 patients with leukemia who received either craniospinal irradiation or cranial irradiation combined with intrathecal methotrexate were evaluated by standardized neurologic and psychologic examinations before and after irradiation. Their performance was compared with that of 27 controls who received irradiation to parts of the body other than the cranium. In a retrospective study, 11 patients with leukemia receiving prophylactic craniospinal irradiation and 12 controls with the disease not receiving such therapy were followed from the second year after either irradiation or the initial hematologic remission. Eighteen months after irradiation in the prospective study and four years after irradiation in the retrospective study, no noteworthy neurologic or psychologic differences were found between subjects and controls

  16. Nutritional assessment and serum zinc and copper concentration among children with acute lymphocytic leukemia: a longitudinal study

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    Ursula Rohr Sgarbieri

    Full Text Available CONTEXT AND OBJECTIVE: When undergoing chemotherapy and/or radiotherapy, children with acute lymphocytic leukemia may present important nutritional disorders because of the gastrointestinal toxicity of most chemotherapy agents or the effects of radiation on the organism. These patients may also present changes in their serum concentrations of trace elements such as zinc and copper. The present study aimed to follow anthropometric parameters and serum levels of zinc and copper in a group of children under treatment for acute lymphocytic leukemia. DESIGN AND SETTING: Longitudinal study, at the Pediatric Section of Hospital das Clínicas, Ribeirão Preto, Brazil. METHODS: Forty-five children with acute lymphocytic leukemia were studied. Anthropometric parameters such as weight and height and the daily intakes and serum levels of copper and zinc were recorded at diagnosis and during the treatment. RESULTS: During the initial phase of the treatment, there was an increase in energy intake accompanied by weight gain. However, during the later phases of treatment there was a reduction in energy intake with accompanying weight loss. Decreased growth rate during treatment was more pronounced in children with high-risk acute lymphocytic leukemia, probably due to radiation therapy. Serum zinc levels remained basically unaltered during the treatment, whereas copper levels decreased dramatically with the beginning of treatment. CONCLUSIONS: The treatment given to children with acute lymphocytic leukemia has an important effect on their linear growth rate and nutritional status, and also on their serum copper levels.

  17. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    International Nuclear Information System (INIS)

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-01-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas

  18. Meningosis prophylaxis with intrathecal /sup 198/Au-colloid and methotrexate in childhood acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Metz, O.; Stoll, W.; Plenert, W.

    1982-01-01

    Since 1972, telecobalt irradiation plus intrathecal methotrexate (ITMTX) has been successfully replaced in Jena by intrathecal colloidal radioactive gold (/sup 198/Au) plus ITMTX for meningosis prophylaxis in leukemia. Seventy-three children with acute lymphocytic leukemia (ALL) were given 1.24-4.89 mCi (45.8-181 MBq) of colloidal 198Au IT after successful initiation of remission. During cytostatic therapy, the following relapses occurred: meningosis leucaemica, five patients (6.8%); bone-marrow relapse and the meningosis leucaemica, one patient; and bone-marrow relapse, 20 patients (27.4%). In 18 children, combination chemotherapy was terminated after two and a half or three years of treatment. After that time, one meningeal relapse and six bone-marrow relapses occurred. Within the first 24 hours after application of radioactive gold, headaches, vomiting, and fever occurred in less than 10% of the children. An apathy syndrome, leukecephalopathy, or severe infections, were not observed in a single case. Radioactive gold spreads in the subarachnoid space and is phagocytized by the arachnoidea. The tumoricide effect extends selectively over the space of distribution of the latent meningosis leucaemia. The cerebral parenchyma remains unaffected by radiation. Thus, radioactive gold may be preferable to telecobalt irradiation in preventing central nervous system leukemia

  19. The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Moss, H.A.; Nannis, E.D.; Poplack, D.G.

    1981-01-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia

  20. Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Erikson, J.; Griffin, C.A.; Ar-Rushdi, A.

    1986-01-01

    In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as breakpoint cluster region (bcr). The same cytogenetically indinstinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study the authors have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL they found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, they observed normal size bcr and c-alb transcripts in an ALL cell line carrying the t(9;22) translocation. They conclude, therefore, that if c-alb is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML

  1. [Research progress on cellular and molecular genetics of acute non-lymphocytic leukemia].

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    Xiong, Wen-Yan; Tu, San-Fang; Lu, Zhi-Gang; Li, Yu-Hua

    2010-04-01

    With the extensive application of cellular and molecular genetic techniques in the research of acute leukemia (AL), the diagnosis of AL type has been developed from FAB typing which was based on morphological classification in 1976 to MICM typing in 2001. This progress highlights the importance of cellular and molecular genetic changes in the diagnosis of leukemia. The cellular and molecular genetic abnormalities in acute leukemia can make the stratification of risk and give the guidance for prognosis and treatment, which is also critical for the development of new drugs. This article has focused on chromosomal abnormalities, fusion gene expression and their relationship with the leukemia diagnosis, prognosis and treatment. This article is also a concise review on several common gene mutations in cytogenetics of ANLL for the assessment of disease prognosis. In recent years, further exploration of molecular cytogenetic mechanisms of various types of leukemia in ANLL contributed to the development of new therapeutic strategy for leukemia.

  2. Liver and spleen MRI findings in virus-associated hemophagocytic syndrome in a patient with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Zilkha, A.; Madan, V.; Leonidas, J.C.; Valderrama, E.

    1998-01-01

    Virus-associated hemophagocytic syndrome is characterized by the phagocytosis of erthythrocytes and other blood elements in multiple organ systems, especially the liver and spleen. Magnetic resonance imaging (MRI) can suggest this diagnosis in the proper clinical setting by demonstrating multiple, rounded signal voids in the spleen corresponding to hemosiderin deposition. We report a patient with virus-associated hemophagocytic syndrome during the course of acute lymphocytic leukemia and MRI findings that suggested the preoperative diagnosis. (orig.)

  3. Liver and spleen MRI findings in virus-associated hemophagocytic syndrome in a patient with acute lymphocytic leukemia

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    Zilkha, A.; Madan, V.; Leonidas, J.C. [Division of Pediatric Radiology, Island Jewish Medical Center, New Hyde Park, NY (United States); Valderrama, E. [Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY (United States)

    1998-12-01

    Virus-associated hemophagocytic syndrome is characterized by the phagocytosis of erthythrocytes and other blood elements in multiple organ systems, especially the liver and spleen. Magnetic resonance imaging (MRI) can suggest this diagnosis in the proper clinical setting by demonstrating multiple, rounded signal voids in the spleen corresponding to hemosiderin deposition. We report a patient with virus-associated hemophagocytic syndrome during the course of acute lymphocytic leukemia and MRI findings that suggested the preoperative diagnosis. (orig.) With 1 fig., 4 refs.

  4. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-01-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  5. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

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    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-11-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  6. Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

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    Jain, Punit; Kanagal-Shamanna, Rashmi; Wierda, William; Ferrajoli, Alessandra; Keating, Michael; Jain, Nitin

    2017-09-01

    Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  7. Skeletal scintigraphy and radiography at onset of acute lymphocytic leukemia in children

    International Nuclear Information System (INIS)

    Clausen, N.; Gotze, H.; Pedersen, A.; Riis-Petersen, J.; Tjalve, E.

    1983-01-01

    /sup 99m/Technetium skeletal scintigraphy performed at the time of diagnosis was compared with pain and radiographs in 24 children with acute lymphocytic leukemia. Localized intense uptake of the labeled compound in one or several metaphyses and increased uptake in diaphyses were typical findings by scintigraphy. The skeleton of each child was subdivided into 18 regions, and investigated for the presence of pain and for possible radiographic and scintigraphic abnormalities. In a total of 432 regions (18 regions in each of 24 children), pain was present in 23 regions, radiographic anomalies in 54 regions, and abnormal technetium uptake in 98 regions. Signs and symptoms were most often found in the lower extremities. Pain and radiographic or scintigraphic abnormalities were not regularly found in the same skeletal regions. The individual number of radiographic abnormalities was negatively correlated with age, whereas the number of regions with abnormal technetium uptake was positively correlated with age. No significant correlation was found between the number of abnormal scintigraphic or radiographic regions and the clinical outcome of the disease

  8. Effects of cranial radiation on hearing in children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Thibadoux, G.M.; Pereira, W.V.; Hodges, J.M.; Aur, R.J.

    1980-01-01

    The hearing sensitivity of 61 children with acute lymphocytic leukemia who were admitted to our Total Therapy IX study between December 1975 and July 1977 was studied. Their treatment included combined chemotherapy, 2400 rads of cranial radiation, and intrathecal methotrexate. Subjects initially received an otologic examination and middle ear function testing. Audiometric testing was not done until ears were free of outer or middle ear pathology. If the child had no outer or middle ear disease, audiometric thresholds were obtained for the test frequencies: 500, 1000, 2000, 4000, 6000, and 8000 Hz. Pure-tone thresholds were obtained before irradiation (61 patients) and at 6, 12, and 36 months thereafter (49, 46, and 22 patients, respectively). The median age of time of baseline testing was 10 years, 2 months. A paired sample test based on group data was used to test whether there were any significant changes from the threshold values at 6, 12, and 36 months after irradiation. Thresholds were not significantly affected for any test frequency at any test time. Assessments of individual audiograms indicated that none of the children had any significant reductions in hearing levels at the end of the third year after cranial irradiation

  9. Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

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    Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

    2011-01-13

    Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

  10. Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

    Directory of Open Access Journals (Sweden)

    Stefano Mattioli

    Full Text Available Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS as risk factors for Acute non-Lymphocytic Leukemia (AnLL were investigated.Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR and 95% confidence intervals (95%CI conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene.Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05. An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07. No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS.This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

  11. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Waddell

    2017-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  12. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Waddell, Benjamin; Belcher, Chris; Willey, Emily

    2017-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  13. MR detection of transient leukoencephalopathy in children treated for acute lymphocytic leukemia and correlation with subsequent neuropsychological deficiencies

    International Nuclear Information System (INIS)

    Wilson, D.A.; Nitscchke, R.; Sexauer, C.; Bowman, M.; Chaffin, M.; Prince, J.R.

    1990-01-01

    This paper determines with MR imaging the leukoencephalopathic (LE) in children undergoing chemotherapy for acute lymphocytic leukemia (ALL) and the significance of these changes in predicting subsequent neuropsychological (NP) deficiencies. Cranial MR imaging was performed on 25 children at diagnosis (1st week), beginning consolidation (7th week), halfway through consolidation (15th week), beginning maintenance (26th week), and at 1-y intervals following diagnosis. Each T2-weighted axial sequence was graded according to normal (0), mild (1), moderate (2), or severe (3) LE changes. Fifteen children to date have undergone a battery of standard NP tests. The LE changes and NP deficiencies were correlated

  14. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  15. Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  16. The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    Cheng, Yuping; Luo, Zebin; Yang, Shilong; Jia, Ming; Zhao, Haizhao; Xu, Weiqun; Tang, Yongmin

    2015-02-01

    Absolute lymphocyte count (ALC) after therapy has been reported to be an independent prognostic factor for clinical outcome in leukemia. This study mainly analyzed ALC at interim of therapy on day 22 (ALC-22) and the ratio of ALC-22 to ALC at diagnosis (ALC-0) on the impact of survival and the relation of ALC to lymphocyte subsets in 119 pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients. Univariate analysis revealed that ALC-22/ALC-0 ratio <10% was significantly associated with inferior overall survival (OS) (hazard ratio (HR)=12.24, P=0.0014) and event-free survival (EFS) (HR=3.3, P=0.0046). In multivariate analysis, ALC-22/ALC-0 ratio remained an independent prognostic factor for OS (HR=6.92, P=0.0181) and EFS (HR=2.78, P=0.0329) after adjusting for age, white blood cell (WBC) count and minimal residual disease (MRD) status. A Spearman correlation test showed that CD3+ T cells had a negative correlation with ALC-0 (r=-0.7204, P<0.0001) and a positive correlation with ALC-22 (r=0.5061, P=0.0071). These data suggest that ALC-22/ALC-0 ratio may serve as a more effective biomarker to predict survival in pediatric B-ALL and ALC is mainly associated with CD3+ T cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. MLL-AF4 fusion transcripts in Acute Lymphocytic Leukemia patientsin Children hospital of Tabriz

    Directory of Open Access Journals (Sweden)

    Amir Monfaredan

    2014-08-01

    Full Text Available Background: MLL-AF4 positive Leukemias comprise about 50-70% of acute lymphoid leukemias in children and about 5% of adolescents and adults Despite recent advances in the treatment of hematologic malignancies of children with ALL in particular, but it seems that poor results are obtained from treating this type of malignancy. Perhaps it is due to the lack of enough knowledge about the expression pattern of the fusion gene induced by chromosomal translocations. This study aims to consider several aspects of the common chromosomal disorder, t (4 11: due to lack of accurate statistical results for this type of translocation in our country, acceptable results are provided Sprevalence of isoforms of recombinant genes involved in MLL-AF4 are explained. Materials and methods: Of 36 patients with ALL between 4 months -11 years of age, peripheral blood sampling was done and total RNA extracted and cDNA was made. Then cDNA was amplified in two steps with the PCR and Nested PCR reactions. After electrophoresis the products were compared and analyzed in comparison with the internal control. Results: The results showed that MLL-AF4 recombinant gene expression in the age between 4 to 12 months range is maximum in the second stage by Nested PCR. Also the highest frequency of fusion isoforms of the gene involved in the same age range is e11-e4 isoform with the frequency of 0.13. Conclusion: It seems that investigation of translocation and chromosomal abnormalities using molecular techniques is one of the most accurate and suitable methods for identifying chromosomal characteristics in patients with acute leukemia, particularly ALL.

  18. Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform.

    Science.gov (United States)

    Magnani, Chiara F; Turazzi, Nice; Benedicenti, Fabrizio; Calabria, Andrea; Tenderini, Erika; Tettamanti, Sarah; Giordano Attianese, Greta M P; Cooper, Laurence J N; Aiuti, Alessandro; Montini, Eugenio; Biondi, Andrea; Biagi, Ettore

    2016-08-09

    Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy.

  19. Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926.

    Science.gov (United States)

    Lin, Tara L; Wang, Qiuju H; Brown, Patrick; Peacock, Craig; Merchant, Akil A; Brennan, Sarah; Jones, Evan; McGovern, Karen; Watkins, D Neil; Sakamoto, Kathleen M; Matsui, William

    2010-12-28

    Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL). We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO) inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH) by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone.

  20. [Effect of Heat Shock Protein 90 Inhibitor 17-DMAG on Proliferation and Apoptosis of Acute Lymphocytic Leukemia Cell Line Jurkat].

    Science.gov (United States)

    Ge, Fang-Fang; Guo, Rong; Tian, Wen-Liang; Gao, Feng-Cai; Sun, Ling; Jiang, Zhong-Xing

    2017-08-01

    To explore the effect of heat shock protein 90(HSP90) inhibitor 17-DMAG, an inhibitor specific for heat shock protein 90, on the proliferation and apoptosis of acute lymphocytic leukemia cell lines Jurkat. Jurkat cells were collected, then were treated with 17-DMAG. The expression of HSP90 was examined by semi-quantitative RT-PCR analysis, the effect of 17-DMAG on cell proliferation were detected by using WST, and cell apoptosis were detected by using flow cytometry with Annexin V/PI double stenining. After Jurkat cells were treated with different concentrations of 17-DMAG for 48 hours, the HSP90 mRNA expression decreased significantly in dose dependent manner (r=0.9530, PJurkat cells were treated with 17-DMAG for 48 h; after treating Jurkat cell with 17-DMAG, the cell proliferation was inhibited(r=0.9903, PJurkat cell proliferation and induce the Jurkat cell apoptosis.

  1. Health-Related Quality of Life, Depression, Anxiety, and Self-Image in Acute Lymphocytic Leukemia Survivors.

    Science.gov (United States)

    Baytan, Birol; Aşut, Çiğdem; Çırpan Kantarcıoğlu, Arzu; Sezgin Evim, Melike; Güneş, Adalet Meral

    2016-12-01

    With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children's Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life InventoryTM were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and follow-up programs should be implemented for children during and after treatment for ALL.

  2. Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926.

    Directory of Open Access Journals (Sweden)

    Tara L Lin

    Full Text Available Conserved embryonic signaling pathways such as Hedgehog (Hh, Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL. We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone.

  3. A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure-response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm.

    Science.gov (United States)

    Sielken, Robert L; Valdez-Flores, Ciriaco

    2015-11-05

    Excess cancer risks associated with 1,3-butadiene (BD) inhalation exposures are calculated using an extensive data set developed by the University of Alabama at Birmingham (UAB) from an epidemiology study of North American workers in the styrene butadiene rubber (SBR) industry. While the UAB study followed SBR workers, risk calculations can be adapted to estimate both occupational and general population risks. The data from the UAB SBR study offer an opportunity to quantitatively evaluate the association between cumulative exposure to BD and different types of cancer, accounting for the number of tasks involving high-intensity exposures to BD as well as confounding associated with the exposures to the multiple other chemicals in the SBR industry. Quantitative associations of BD exposure and cancer, specifically leukemia, can be further characterized by leukemia type, including potential associations with acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML), and the groups of lymphoid and myeloid neoplasms. Collectively, these multiple evaluations lead to a comprehensive analysis that makes use of all of the available information and is consistent with the risk assessment goals of the USEPA and other regulatory agencies, and in line with the recommendations of the USEPA Science Advisory Board. While a range of cancer risk values can result from these multiple factors, a preferred case for occupational and general population risk is highlighted. Cox proportional hazards models are used to fit exposure-response models to the most recent UAB data. The slope of the model with cumulative BD ppm-years as the predictor variable is not statistically significantly greater than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined. The slope for CLL is statistically significantly different from zero. The slope for myeloid neoplasms is not statistically

  4. Biological and clinical meaning of myeloid antigen expression in the acute lymphocytic leukemia in children

    International Nuclear Information System (INIS)

    Marsan Suarez, Vianed; Sanchez Segura, Miriam; Socarras Ferrer, Bertha B; Valle Perez, Lazaro O del

    2009-01-01

    In 238 children presenting with acute lymphoid leukemia (ALL) authors studied the possible association between the myeloid antigens expression with determined biologic and clinic features at disease onset. The cellular immunophenotyping was performed by ultraimmunocytochemical method. From the total of diagnosed ALLs, the 21,8% were LLA-Mi+. There was a lymphadenopathies predominance (71,2%), splenomegaly (65,4%) and hepatomegaly (57,7%) in patients with LLA-Mi+ and very significant differences (p =0,003, p = 0,0068, and p = 0,000, respectively. There was also alight predominance of mediastinum adenopathies, CNS infiltration and hemorrahagic manifestations in patients with LLA-Mi+, no statistically significant. Results showed that in our patients the myeloid antigen expression on the lymphoid blasts influenced on appearance of determined presentation of morphologic and clinical features in children

  5. Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Daley, J

    1987-01-01

    We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily...... irradiated autologous thymocytes as feeder cells) resulted in growth in 6-14% of the wells (mean, 11%) with cells with mature T lymphocyte phenotype. Two-color fluorescence analysis of outgrowing cultures furthermore ascertained that these cells had differentiated through a phase of simultaneous expression...... of T4 and T8 antigens and at the same time expression of the thymocyte-associated T6 antigens. Thus, given the fact that 10-20% of T cell acute lymphoblastic leukemia (T-ALLs) are CALLA+, we have been able to identify a human prethymic T lymphocyte population that might be the normal counterpart...

  6. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  7. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2018-01-26

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  8. Immunization practices in acute lymphocytic leukemia and post-hematopoietic stem cell transplant in Canadian Pediatric Hematology/Oncology centers.

    Science.gov (United States)

    Top, Karina A; Pham-Huy, Anne; Price, Victoria; Sung, Lillian; Tran, Dat; Vaudry, Wendy; Halperin, Scott A; De Serres, Gaston

    2016-04-02

    There are no Canadian immunization guidelines for children treated for malignancy. Guidelines do exist for patients who underwent hematopoietic stem cell transplant (HSCT), but they provide broad timeframes for initiating vaccination; there is no standard schedule. The optimal approach to immunization in these populations is unclear. We sought to describe immunization practices at Canadian Pediatric Hematology/Oncology centers. A 43-item online questionnaire was distributed to the 16 programs in the C(17) research network of pediatric hematology/oncology centers to capture information on timing and criteria for immunization of patients with acute lymphocytic leukemia (ALL) and those who have undergone HSCT. At each center, 1-2 physicians or pharmacists completed the survey to reflect center-wide immunization practices. Responses were received from 11/16 (69%) programs; 11 respondents reported on practices for patients with ALL and 9 reported on practices for patients who are post-HSCT. In 5/11 ALL programs (45%) re-immunization is recommended routinely after chemotherapy, starting 3-6 months post-chemotherapy. In HSCT programs, timing of pneumococcal conjugate vaccination (PCV) varied from 3 months post-HSCT (4 programs) to 12 months post-HSCT (4 programs). Live vaccines were administered 24 months post-HSCT in 8/9 programs. All HSCT programs considered graft-versus-host-disease and 7 considered discontinuation of immunosuppression in immunization decisions. Pediatric hematology/oncology programs were divided in regards to re-immunization of patients with ALL post-chemotherapy. After HSCT, timing of PCV administration varied, with 4 programs initiating immunization later than Canadian guidelines recommend (3-9 months post-HSCT). These findings suggest a need to standardize immunization practices in these populations.

  9. Laboratory diagnosis of chronic myelomonocytic leukemia and progression to acute leukemia in association with chronic lymphocytic leukemia: morphological features and immunophenotypic profile

    OpenAIRE

    Santos, Iris Mattos; Franzon, Carine Muniz Ribeiro; Koga, Adolfo Haruo

    2012-01-01

    Chronic myelomonocytic leukemia is a clonal stem cell disorder that is characterized mainly by absolute peripheral monocytosis. This disease can present myeloproliferative and myelodysplastic characteristics. According to the classification established by the World Health Organization, chronic myelomonocytic leukemia is inserted in a group of myeloproliferative/myelodysplastic disorders; its diagnosis requires the presence of persistent monocytosis and dysplasia involving one or more myeloid ...

  10. Allogeneic hematopoietic stem cell transplantation as immunotherapy : B lymphocytes versus leukemia

    NARCIS (Netherlands)

    Gillissen, M.A.

    2018-01-01

    Research described in this thesis focuses on the role of B lymphocytes in graft versus leukemia responses following allogeneic hematopoietic stem cell transplantation (HSCT) as treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Acute myeloid leukemia (AML) and high-risk

  11. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  12. Chronic Lymphocytic Leukemia: Current Concepts.

    Science.gov (United States)

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

    2015-10-01

    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  14. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  15. General Information about Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... in adults. It often occurs during or after middle age; it rarely occurs in children. Enlarge Anatomy of ... Approved for Chronic Lymphocytic Leukemia for more information. New types of treatment are being tested in clinical ...

  16. Orbital involvement in chronic lymphocytic leukemia.

    Science.gov (United States)

    Skinnider, L F; Romanchuk, K G

    1984-04-01

    In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults.

  17. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds w...

  18. Acute lymphocytic leukemia (ALL)

    Science.gov (United States)

    ... lymph nodes, and spleen Signs of bleeding (petechiae, purpura ) Blood tests may include: Complete blood count (CBC), ... your health care provider if you or your child develops symptoms of ALL. Prevention The risk of ...

  19. Genetics Home Reference: acute promyelocytic leukemia

    Science.gov (United States)

    ... Home Health Conditions Acute promyelocytic leukemia Acute promyelocytic leukemia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Acute promyelocytic leukemia is a form of acute myeloid leukemia, a ...

  20. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

  1. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.

    Science.gov (United States)

    Horton, Terzah M; Sposto, Richard; Brown, Patrick; Reynolds, C Patrick; Hunger, Stephen P; Winick, Naomi J; Raetz, Elizabeth A; Carroll, William L; Arceci, Robert J; Borowitz, Michael J; Gaynon, Paul S; Gore, Lia; Jeha, Sima; Maurer, Barry J; Siegel, Stuart E; Biondi, Andrea; Kearns, Pamela R; Narendran, Aru; Silverman, Lewis B; Smith, Malcolm A; Zwaan, C Michel; Whitlock, James A

    2010-07-01

    One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Copyright 2010 Wiley-Liss, Inc.

  2. [Triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells via inhibiting transcription of human endogenous retrovirus HERV-K Np9 gene].

    Science.gov (United States)

    Chen, Jianghua; Zheng, Weiwei; Jiang, Xudong; Lu, Xiaoya; Xu, Rongzhen

    2015-05-01

    To investigate the molecular?mechanisms by which triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells. MTT assay was employed to detect the proliferation inhibition of Jurkat cells by triptolide, and the IC50 was calculated by OriginPro8. Flow cytometry was used to analyze apoptosis of Jurkat cells. Np9 mRNA levels were detected by RT-PCR and analyzed quantitatively by Kodak 1D 3.6 software. Correlation between the inhibition of Np9 transcription and the cell apoptosis was analyzed by SPSS 19.0.Western blotting was employed to determine Np9 downstream signaling molecules c-myc, β-catenin, ERK, AKT and Notch1 protein level in Jurkat cells after exposure to different concentrations of triptolide for 48 h. Triptolide treatment resulted in dose-dependent inhibition of Jurkat cells proliferation and its IC50 was 12.7 nmol/L. Triptolide induced apoptosis of Jurkat cells in dose- dependent manner. Furthermore, triptolide inhibited Np9 mRNA transcription level in Jurakt cells in a dose-dependent manner. There was a correlation between the triptolide-mediated the apoptosis and the inhibition of Np9 transcription of Jurkat cells (R(2)=0.907). Western blotting results displayed that triptolide inhibited transcription levels of Np9 mRNA with a concomitant decrease of its downstream signaling molecules c-myc, β-catenin, ERK, AKT and Notch1 at protein levels. Inhibition of HERV-K Np9 mRNA and its downstream signaling molecules c-myc, β-catenin, ERK, Akt and Notch1 protein might be one of important molecular?mechanisms by which triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells.

  3. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds......,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia compounds....

  4. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  5. Caring for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Elphee, Erin E

    2008-06-01

    Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed form of leukemia in the Western world, accounting for approximately 20%-30% of all cases of leukemia. Despite recent medical and scientific advances, the literature on the subjective experience and nursing care of patients diagnosed with CLL remains scarce and sporadic. This article provides a brief overview on the pathophysiology, clinical characteristics, and treatment options of CLL with focus placed on implications for nursing care. Fatigue, the most common symptom reported by patients, and infection, the leading cause of disease-related deaths, also will be addressed. Emerging data examining quality of life and the incidence of anxiety and depression in this patient population will be reviewed, and strategies aimed at addressing the educational needs of patients and family members will be discussed.

  6. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was re...... from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL....

  7. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-11-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests.

  8. Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children

    International Nuclear Information System (INIS)

    Freeman, A.I.; Weinberg, V.; Brecher, M.L.

    1983-01-01

    The authors compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation. The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group. Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate; there was no difference in the rate of hematologic relapse. Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation

  9. Propiece IL-1α facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-κB and SP1.

    Science.gov (United States)

    Zhang, Yinsheng; Yu, Xiao; Lin, Dandan; Lei, Lei; Hu, Bo; Cao, Fengzhang; Mei, Yu; Wu, Depei; Liu, Haiyan

    2017-02-28

    Interleukin 1α (IL-1α) is a pro-inflammatory cytokine that possesses multiple immune-regulatory functions. It is mainly expressed as the cell-associated form and not actively secreted in healthy tissues. The intracellular IL-1α has been shown to be a chromatin-associated cytokine and can affect transcription. There are spontaneous expressions of IL-1α in acute lymphocytic leukemia (ALL) blasts. However, the role of nuclear-localized IL-1α in ALL is not clear. Here we showed that overexpression of the nuclear form of IL-1α (propiece IL-1α) could promote proliferation and reduce apoptosis of T-ALL cells. It also increased the ALL cells' resistance to low serum concentration and cisplatin treatment. In vivo growth of the T-ALL cells overexpressing the propiece IL-1α were also enhanced compared to the control cells. Microarray analysis revealed many changes in gene expressions related to cell growth and stress, including a group of metallothionein genes. Moreover, the expressions of transcription factors, NFκB and specific protein 1 (SP1), were up-regulated by propiece IL-1α. Propiece IL-1α could bind to the promoter of SP1 and a binding sequence logo was identified. Therefore, nuclear expression of propiece IL-1α can facilitate the growth of T-ALL cells possibly through the activation of NFκB and SP1.

  10. Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-Hodgkins lymphoma: a study of pulsatile growth hormone and gonadotropin secretions

    International Nuclear Information System (INIS)

    Mauras, N.; Sabio, H.; Rogol, A.D.

    1988-01-01

    To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data

  11. Latent central nervous disorders observed in the acute lymphocytic leukemia children after treatment. Comparison between the evaluation of electroencephalogram and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Itokazu, Naoya; Kiue, Kouichiro; Inoue, Shinobu; Ohba, Kenichi; Sonoda, Tohru; Sugimoto, Tohru [Miyazaki Medical Coll., Kiyotake (Japan)

    1996-02-01

    For 8 children with acute lymphocytic leukemia (ALL) which finished the treatment, the existence of the latent central nervous disorders was examined and was compared of MRI and brain wave. In the MRI, the T2-weighted image showed the large number of nodule abnormal high signal lesions in the cerebral white matter in 2 of 8 patients, and one of these patients was accompanied by the slight cerebrum atrophy. There was the diffuse high signal tendency of periventricular white matter and the slight expansion of ventriculus cerebri in one patient. In the brain wave, there was the abnormality of the basic pattern in 3 of 8 patients, and there was the slowing tendency in 2. There was no case which showed the paroxysm extraordinary wave. The patient who showed the abnormality by the MRI was all accompanied by the brain wave abnormality. The frequency of the latent central nervous disorders incidence in ALL treatment was high (3/8 on the brain wave, 5/8 on the MRI). The brain wave was supersensitively able to detect the failure than the MRI, if the finding of the basic pattern is evaluated in detail. (A.N.).

  12. Chronic lymphocytic leukemia: concepts and observations

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.

    1977-01-01

    Thirty-five patients with chronic lymphocytic leukemia (CLL) were studied for assessment of total body leukemic mass and abnormality in T-lymphocyte function associated with clinical stages of CLL. Total body potassium (TBK), an indicator of lean body mass, was found to correlate well with increase in the clinical stage of the disease. Use of TBK for monitoring the regression and relapse of leukemic load is suggested. No correlation was found between whole cell and nuclear volumes of lymphocytes in CLL patients and clinical stages of the disease. Blast transformation and proliferation under phytohemagglutinin (PHA) stimulation appeared to be normal in purified T cells of early stages and abnormal in the late stages of disease.

  13. Maintenance therapy of childhood acute lymphoblastic leukemia revisited—Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard

    2016-01-01

    BACKGROUND: 6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose...

  14. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); 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(15;17)(q22;q12); 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 Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Acute Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  16. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2018-02-28

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  17. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  18. Leukemia

    International Nuclear Information System (INIS)

    Mabuchi, Kiyohiko; Kusumi, Shizuyo

    1992-01-01

    Leukemia is the first malignant disease found among A-bomb survivors. Leukemia registration has greatly contributed to epidemiological and hematological studies on A-bomb radiation-related leukemia and other hematopoietic diseases, consisting of community population and the RERF Life Span Study (LSS) sample (approximately 120,000 persons containing A-bomb survivors). Using the fixed LSS cohort, the prevalence rate of leukemia reached the peak during the years 1950-1954, and thereafter, it has been gradually decreased. However, risk patterns for leukemia are still unsolved: has leukemia risk increased in recent years?; are serial changes in leukemia risk influenced by age at the time of exposure (ATE)?; is there variation between Hiroshima and Nagasaki?; and others. To solve these questions, leukemia data are now under analysis using the revised DS86. Relative risk for leukemia, especially chronic myelogenous leukemia and acute lymphocytic leukemia (ALL), is found to be linearly increased with increasing bone marrow doses. Serial patterns of both excess risk and excess relative risk have revealed that leukemia risk is high at 5-10 years after A-bombing in younger A-bomb survivors ATE. The influence of age ATE on serial changes is noticeable in ALL. Another factor involved in the prevalence of leukemia is background (spontaneously developed leukemia), which is the recent interest because young A-bomb survivors ATE reach the cancer-prone age. (N.K.)

  19. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia.

    Science.gov (United States)

    de Leeuw, David C; van den Ancker, Willemijn; Denkers, Fedor; de Menezes, Renée X; Westers, Theresia M; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Smit, Linda

    2013-04-15

    Classification of acute leukemia is based on the commitment of leukemic cells to the myeloid or the lymphoid lineage. However, a small percentage of acute leukemia cases lack straightforward immunophenotypical lineage commitment. These leukemias of ambiguous lineage represent a heterogeneous category of acute leukemia that cannot be classified as either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). The lack of clear classification of acute leukemias of ambiguous lineage as either AML or ALL is a hurdle in treatment choice for these patients. Here, we compared the microRNA (miRNA) expression profiles of 17 cases with acute leukemia of ambiguous lineage and 16 cases of AML, B-cell acute lymphoid leukemia (B-ALL), and T-cell acute lymphoid leukemia (T-ALL). We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to AML, B-ALL, or T-ALL. We show that by using only 5 of the most lineage-discriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL. Our results indicate the presence of a myeloid or lymphoid lineage-specific genotype, as reflected by miRNA expression, in these acute leukemias despite their ambiguous immunophenotype. miRNA-based classification of acute leukemia of ambiguous lineage might be of additional value in therapeutic decision making.

  20. Case Report: A child with acute lymphocytic leukaemia

    African Journals Online (AJOL)

    The patient was a child aged 5 years who had been diagnosed to have acute lymphocytic leukemia (ALL). Chemotherapy was given with wysolone, vincristine, daunomycin, l-asparaginase, and intrathecal methotrexate. In addition he was given fluconazole and co-trimoxazole to cover infections during the induction period ...

  1. [Acute myeloid Leukemia].

    Science.gov (United States)

    Braess, Jan

    2016-11-01

    Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future.The basis of curative treatment is intensive combination chemotherapy comprizing cytarabine and an anthracycline ("7 + 3" regimen). The prolonged duration of aplasia can be reduced significantly by accelerated therapy ("S-HAM" regimen). Following achievement of a complete remission patients with a low risk of relapse - based on genetic and clinical features - receive chemotherapy based consolidation therapy whereas high risk patients - and potentially also those with an intermediate risk - receive an allogeneic stem cell transplantation. Whereas adding the rather unspecific tyrosinekinase inhibitor sorafenib to standard treatment in unselected AML patients has not improved overall survival (OS), the addition of midostaurin to standard therapy in the selected group FLT3 mutated patients has resulted in a moderate but significant OS benefit.Real world data show that in patients below 50 years a cure rate of ca. 50 % can be achieved. However less than 10 % of patients above the age of 70 will be alive after five years even after intensive treatment. Therefore when curative and intensive treatment is deemed impossible the therapeutic standard in elderly and unfit patients used to be low-dose cytarabine with an average OS of 4 months. This has now been replaced by a new standard of care of hypomethylating agents - azacytidine and decitabine - which both achieve higher remission rates and show strong trends towards a prolonged OS

  2. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Weisser, Martin; Yeh, Ru-Fang; Duchateau-Nguyen, Guillemette

    2014-01-01

    Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has significantly improved patient outcomes in chronic lymphocytic leukemia (CLL). Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined. We...

  3. Orbital involvement in chronic lymphocytic leukemia: Case report

    Directory of Open Access Journals (Sweden)

    Romana Rotdajč

    2012-12-01

    Conclusions: In patients with chronic lymphocytic leukemia, progression of the disease should be suspected at impairment of the eye and the surrounding tissues. Monotherapy with rituximab can be successful, which is indicated particularly in elderly patients.

  4. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    Science.gov (United States)

    ... Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) ... Coping Print en español Leucemia linfoblástica aguda About Leukemia Leukemia is a type of cancer that affects ...

  5. Acute leukemias of ambiguous origin.

    Science.gov (United States)

    Porwit, Anna; Béné, Marie C

    2015-09-01

    This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated. We emphasize that a comprehensive approach to immunophenotyping is required to accurately establish the diagnosis of MPAL. Flow cytometry immunophenotyping using a large panel of antibodies is needed as well as confirmatory immunohistochemical analysis and cytochemistry studies for myeloperoxidase and nonspecific esterase. We discuss technical issues in determining blast lineage and possible pitfalls in MPAL diagnosis. In particular, rare cases of B-acute lymphoblastic leukemia (B-ALL) can express myeloperoxidase but are otherwise consistent with B-ALL and should be treated as such. Last, we review the differential diagnosis between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation. There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough. Copyright© by the American Society for Clinical Pathology.

  6. Recent therapeutic advances in chronic lymphocytic leukemia

    Science.gov (United States)

    Bose, Prithviraj; Gandhi, Varsha

    2017-01-01

    The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs. Thus, successful therapeutic targeting of the B-cell receptor signaling pathway and of the Bcl-2 anti-apoptotic protein with small molecules has now made chemotherapy-free approaches possible, hopefully mitigating the risk of development of therapy-related myeloid neoplasms and making eventual cure of CLL with the use of optimal drug combinations a realistic goal. Most importantly, these therapies have demonstrated unprecedented efficacy in patients with deletion 17p/TP53 mutation, a subset that historically has been very difficult to treat. However, as we gain more experience with the newer agents, unique safety concerns and resistance mechanisms have emerged, as has the issue of cost, as these expensive drugs are currently administered indefinitely. Accordingly, novel laboratory-based strategies and clinical trial designs are being explored to address these issues. The availability of whole exome/genome sequencing has given us profound insights into the mutational landscape of CLL. In this article, we highlight some of the most impactful advances since this topic was last reviewed in this journal. PMID:29152232

  7. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...

  8. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-22

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  9. [Occurrence of associated tumours in chronic lymphocytic leukemia].

    Science.gov (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt

    2016-10-01

    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  10. Emerging immunological drugs for chronic lymphocytic leukemia.

    Science.gov (United States)

    Robak, Pawel; Smolewski, Piotr; Robak, Tadeusz

    2015-09-01

    Over the last few years, several new immunological drugs, particularly monoclonal antibodies (mAbs), immunomodulatory drugs and B-cell receptor (BCR) pathway inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). This article summarizes recent discoveries regarding their mechanism of action, pharmacological properties, clinical activity and toxicity, as well as the emerging role of these agents in CLL. A literature review of mAbs, BCR pathway inhibitors and immunomodulating drugs was conducted of the MEDLINE database via PubMed for articles in English. Publications from 2000 through February 2015 were scrutinized. The search terms used were alemtuzumab, BI 836826, duvelisib ibrutinib, idelalisib, lenalidomide, monoclonal antibodies, MEDI-551, MOR208, obinutuzumab, ocaratuzumab, ofatumumab, ONO-4059, otlertuzumab, spebrutinib, veltuzumab and XmAb5574 in conjunction with CLL. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL. However, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease.

  11. Isochromosome 17q in Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Alhourani, Eyad; Rincic, Martina; Melo, Joana B.; Carreira, Isabel M.; Glaser, Anita; Pohle, Beate; Schlie, Cordula; Liehr, Thomas

    2015-01-01

    In chronic lymphocytic leukemia (CLL), presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH). Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q); surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q) could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12%) here studied CLL cases. Six of those cases (~33%) had the TP53 deletion accompanied by an i(17q). Interestingly, the cases with i(17q) showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q); it may be suggested that the i(17q) presents an even more adverse prognostic marker than TP53 deletion alone. PMID:26697230

  12. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  13. Is there a role for B lymphocyte chimerism in the monitoring of B-acute lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?

    Directory of Open Access Journals (Sweden)

    Yi-Ning Yang

    2015-03-01

    Full Text Available Objective: To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. Methods: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells was made in 20 B-cell acute lymphoblastic leukemia (B-ALL patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT. In the early period after allo-HSCT, the latest establishment of B-cell complete chimerism (CC was observed in a majority of patients. Results: The percentage of donor cells of B-cell lineage was lower than the percent of T-cell lineage in most of the mixed chimerism (MC patients. During graft rejection, the frequency of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and 2/5. When disease relapsed, five patients showed a faster decrease of the donor percent of B-cells than of T- or NK-cells. Only one patient displayed a more rapid decrease in NK-cells than in T- or B-cells. Conclusion: Monitoring of B-cell chimerism after HSCT seems to be valuable for insuring complete engraftment, anticipating graft rejection, and relapse in B-ALL patients. Keywords: B cell acute lymphoblastic leukemia (B-ALL, B-cell, T-cell, Chimerism, Allogeneic hematopoietic stem cell transplantation (allo-HSCT

  14. Occupation and leukemia in Nordic countries

    DEFF Research Database (Denmark)

    Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar

    2012-01-01

    We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

  15. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

    Science.gov (United States)

    Fabbri, Giulia; Holmes, Antony B; Viganotti, Mara; Scuoppo, Claudio; Belver, Laura; Herranz, Daniel; Yan, Xiao-Jie; Kieso, Yasmine; Rossi, Davide; Gaidano, Gianluca; Chiorazzi, Nicholas; Ferrando, Adolfo A; Dalla-Favera, Riccardo

    2017-04-04

    Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival, and signal transduction. In particular, we show that NOTCH1 transactivates MYC via binding to B-cell-specific regulatory elements, thus implicating this oncogene in CLL development. These results significantly extend the role of NOTCH1 in CLL pathogenesis, and have direct implications for specific therapeutic targeting.

  16. Chronic lymphocytic leukemia: an updated review.

    Science.gov (United States)

    Faguet, G B

    1994-09-01

    To review recent advances in the pathogenesis, biology, diagnosis, and management of chronic lymphocytic leukemia (CLL). A literature search restricted to English-language articles, abstracts, book chapters, and reports published between 1975 and 1993 was conducted both electronically using MEDLINE and CANCERLIT and manually using the bibliographies of the electronically retrieved data base. Of approximately 1,000 publications identified for analysis, 233 were selected as representative of important advances in CLL. The last 10 years have witnessed renewed interest in the biology and treatment of CLL, a disease long viewed by clinicians as following an indolent course and perceived by investigators as uninspiring. This interest, based on advances in understanding the lineage and biology of CLL and on the advent of new and more efficacious chemotherapeutic agents, has led to improvements in patient survival and, for the first time, to complete remissions (CRs) in large subsets of patients. As we learn to use these agents better, especially in combination chemotherapy, alternative therapeutic modalities, are being vigorously pursued, including high-dose ablative chemotherapy with allogeneic or autologous bone marrow transplantation (BMT) rescue and the use of powerful tumor-cell target-specific immunoreagents. These therapeutic advances, coupled with the recent availability of molecular probes to ascertain objectively minimal remnant disease posttreatment, provide a basis for developing and assessing ever more efficacious and potentially curative treatment strategies for the management of this disease. For the first time since the original 1924 monograph by Minot and Isaacs, the cure of subsets of patients with CLL appears not to be an unreasonable goal.

  17. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-17

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  18. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

    NARCIS (Netherlands)

    van Attekum, Martijn H. A.; Eldering, Eric; Kater, Arnon P.

    2017-01-01

    The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander

  19. Pneumonia during Remission Induction Chemotherapy in Patients with Acute Leukemia

    Science.gov (United States)

    Garcia, Javier Barreda; Lei, Xiudong; Wierda, William; Cortes, Jorge E.; Dickey, Burton F.; Evans, Scott E.

    2013-01-01

    Background: Pneumonia is a major cause of death during induction chemotherapy for acute leukemia. The purpose of this study was to quantify the incidence, risk factors, and outcomes of pneumonia in patients with acute leukemia. Methods: We conducted a retrospective cohort study of 801 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or acute lymphocytic leukemia (ALL) who underwent induction chemotherapy. Measurements and Main Results: Pneumonia was present at induction start in 85 patients (11%). Of the 716 remaining patients, 148 (21%) developed pneumonia. The incidence rate of pneumonia was higher in MDS and AML than in ALL (0.013 vs. 0.008 vs. 0.003 pneumonias per day, respectively; P risk factors. The case fatality rate of pneumonia was 17% (40 of 233). Competing risk analysis demonstrated that in the absence of pneumonia, death was rare: 28-day mortality was 6.2% for all patients but only 1.26% in those without pneumonia. Compared with patients without pneumonia, patients with pneumonia had more intensive care unit days, longer hospital stays, and 49% higher costs (P Pneumonia after induction chemotherapy for acute leukemia continues to be common, and it is the most important determinant of early mortality after induction chemotherapy. Given the high incidence, morbidity, mortality, and cost of pneumonia, interventions aimed at prevention are warranted in patients with acute leukemia. PMID:23987587

  20. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

    OpenAIRE

    van Attekum, Martijn HA; Eldering, Eric; Kater, Arnon P

    2017-01-01

    The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenv...

  1. Laboratory diagnosis of chronic myelomonocytic leukemia and progression to acute leukemia in association with chronic lymphocytic leukemia: morphological features and immunophenotypic profile Diagnóstico laboratorial de leucemia mielomonocítica crônica agudizada em associação com leucemia linfocítica crônica: aspectos morfológicos e imunofenotípicos

    Directory of Open Access Journals (Sweden)

    Iris Mattos Santos

    2012-01-01

    Full Text Available Chronic myelomonocytic leukemia is a clonal stem cell disorder that is characterized mainly by absolute peripheral monocytosis. This disease can present myeloproliferative and myelodysplastic characteristics. According to the classification established by the World Health Organization, chronic myelomonocytic leukemia is inserted in a group of myeloproliferative/myelodysplastic disorders; its diagnosis requires the presence of persistent monocytosis and dysplasia involving one or more myeloid cell lineages. Furthermore, there should be an absence of the Philadelphia chromosome and the BCR/ABL fusion gene and less than 20% blasts in the blood or bone marrow. Phenotypically, the cells in chronic myelomonocytic leukemia can present myelomonocytic antigens, such as CD33 and CD13, overexpressions of CD56 and CD2 and variable expressions of HLA-DR, CD36, CD14, CD15, CD68 and CD64. The increase in the CD34 expression may be associated with a transformation into acute leukemia. Cytogenetic alterations are frequent in chronic myelomonocytic leukemia, and molecular mutations such as NRAS have been identified. The present article reports on a case of chronic myelomonocytic leukemia, diagnosed by morphologic and phenotypical findings that, despite having been suggestive of acute monocytic leukemia, were differentiated through a detailed analysis of cell morphology. Furthermore, typical cells of chronic lymphocytic leukemia were found, making this a rare finding.A Leucemia Mielomonocítica Crônica (LMMC é uma desordem clonal de células-tronco hematopoiéticas caracterizada principalmente por monocitose absoluta no sangue periférico. Esta doença pode apresentar características de síndromes mielodisplásicas e de doenças mieloproliferativas. De acordo com a classificação estabelecida pela OMS, a LMMC está inserida no grupo de neoplasias mieloproliferativas/mielodisplásicas e seu diagnóstico requer a presença de monocitose persistente no sangue

  2. Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

    Science.gov (United States)

    Kaszuba-Zwoińska, Jolanta; Ćwiklińska, Magdalena; Balwierz, Walentyna; Chorobik, Paulina; Nowak, Bernadeta; Wójcik-Piotrowicz, Karolina; Ziomber, Agata; Malina-Novak, Kinga; Zaraska, Wiesław; Thor, Piotr J

    2015-03-01

    Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

  3. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

    Directory of Open Access Journals (Sweden)

    Caimi Luigi

    2010-11-01

    Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

  4. Genomic Characterization of Acute Leukemias

    Science.gov (United States)

    Chiaretti, Sabina; Gianfelici, Valentina; Ceglie, Giulia; Foà, Robin

    2014-01-01

    Over the past two decades, hematologic malignancies have been extensively evaluated due to the introduction of powerful technologies, such as conventional karyotyping, FISH analysis, gene and microRNA expression profiling, array comparative genomic hybridization and SNP arrays, and next-generation sequencing (including whole-exome sequencing and RNA-seq). These analyses have allowed for the refinement of the mechanisms underlying the leukemic transformation in several oncohematologic disorders and, more importantly, they have permitted the definition of novel prognostic algorithms aimed at stratifying patients at the onset of disease and, consequently, treating them in the most appropriate manner. Furthermore, the identification of specific molecular markers is opening the door to targeted and personalized medicine. The most important findings on novel acquisitions in the context of acute lymphoblastic leukemia of both B and T lineage and de novo acute myeloid leukemia are described in this review. PMID:24968698

  5. Fatal Cryptococcal Meningitis in a Patient With Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Oguzhan Sıtkı Dizdar

    2012-06-01

    Full Text Available Patients with chronic lymphocytic leukemia (CLL are susceptible to infections, especially opportunistic infections. We have described a patient with CLL who had cryptococcal meningitis. Despite lack of previous immunosuppressive treatment history, the patient experienced serious and fatal fungal infection. Physicians should be alert for a diagnosis of cryptococcal meningitis in patient with CLL who developed fever and headache.

  6. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors

    DEFF Research Database (Denmark)

    Xochelli, Aliki; Baliakas, Panagiotis; Kavakiotis, Ioannis

    2017-01-01

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether...... with a significantly (P BcR IG stereotypy further refines prognostication in CLL, superseding...

  7. How does lenalidomide target the chronic lymphocytic leukemia microenvironment?

    NARCIS (Netherlands)

    Kater, Arnon P.; Tonino, Sanne H.; Egle, Alexander; Ramsay, Alan G.

    2014-01-01

    Immunotherapy has emerged as a viable clinical strategy to harness endogenous antitumor T-cell immunity. Lenalidomide is an oral immunomodulatory drug that repairs antitumor T-cell function and is showing efficacy in ongoing chronic lymphocytic leukemia (CLL) and lymphoma clinical trials. This

  8. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    Science.gov (United States)

    ... normal acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer ...

  9. Genetics Home Reference: core binding factor acute myeloid leukemia

    Science.gov (United States)

    ... acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  10. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  11. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia.

    Science.gov (United States)

    Zhou, Qing; Munger, Meghan E; Highfill, Steven L; Tolar, Jakub; Weigel, Brenda J; Riddle, Megan; Sharpe, Arlene H; Vallera, Daniel A; Azuma, Miyuki; Levine, Bruce L; June, Carl H; Murphy, William J; Munn, David H; Blazar, Bruce R

    2010-10-07

    Tumor-induced immune defects can weaken host immune response and permit tumor cell growth. In a systemic model of murine acute myeloid leukemia (AML), tumor progression resulted in increased regulatory T cells (Treg) and elevation of program death-1 (PD-1) expression on CD8(+) cytotoxic T cells (CTLs) at the tumor site. PD-1 knockout mice were more resistant to AML despite the presence of similar percentage of Tregs compared with wild type. In vitro, intact Treg suppression of CD8(+) T-cell responses was dependent on PD-1 expression by T cells and Tregs and PD-L1 expression by antigen-presenting cells. In vivo, the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs. Anti-PD-L1 monoclonal antibody treatment increased the proliferation and function of CTLs at tumor sites, reduced AML tumor burden, and resulted in long-term survivors. Treg depletion followed by PD-1/PD-L1 blockade showed superior efficacy for eradication of established AML. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response. PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease.

  12. Epidemiology of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Pendergrass, T.W.

    1985-01-01

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury

  13. Extramedullary leukemia in children with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

    2017-01-01

    BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...

  14. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  15. An unusual case of acute leukemia.

    Science.gov (United States)

    Fleury, Carole; Passet, Marie; Settegrana, Catherine; Simon, Laurence; Chapiro, Elise; Trinquand, Amélie; Safra Zaghouani, Ines; Uzunov, Madalina; Le Garff-Tavernier, Magali; Armand, Marine; Costopoulos, Myrto

    2017-06-01

    We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified partial rearrangements in immunoglobulin and TCR genes, allowing the monitoring of minimal residual disease. This observation highlights the difficulty to classify some atypical cases of acute leukemias. It emphasizes on the complementarity of cytomorphology, immunophenotyping by flow cytometry and molecular techniques in order to promptly characterize and treat these leukemias.

  16. Epigenetic Regulation of Hematopoiesis and Acute Leukemia

    NARCIS (Netherlands)

    D.G. Valerio (Daria)

    2017-01-01

    markdownabstractIn this thesis we have explored chromatin regulation in acute leukemia and normal hematopoiesis. In doing so, we have focused on the H3K4 methyltransferase MLL1 and the H4K16 acetyltransferase MOF. MLL- and NUP98-translocations are quite common in acute leukemia and even more

  17. acute leukemias immunophenotypes at agakhan university hospital ...

    African Journals Online (AJOL)

    2013-02-01

    Feb 1, 2013 ... specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics ... Conclusion: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these ..... AML-M2 in both pediatric and adult population in. India(15). The proportion of ...

  18. Treatment of Jurkat acute T-lymphocytic leukemia cells by onconase (Ranpirnase) is accompanied by an altered nucleocytoplasmic distribution and reduced expression of transcription factor NF-kappaB.

    Science.gov (United States)

    Tsai, Shwu Y; Ardelt, Barbara; Hsieh, Tze-Chen; Darzynkiewicz, Zbigniew; Shogen, Kuslima; Wu, Joseph M

    2004-12-01

    Onconase (Ranpirnase), a novel ribonuclease isolated from Rana pipiens oocytes, was reported to suppress cancer cell growth in vitro, reduce tumor size in animals, and augment cytotoxicity of several chemotherapeutic agents. Since onconase is currently in phase III clinical trials tested in treatment of mesothelioma, much emphasis has been placed on the mechanism of its anti-tumor activity. Previous studies have shown that onconase-responsive cells become arrested at the G1/S checkpoint of the cell cycle and also undergo apoptosis. A proposed mechanism for these effects is that the enzymatic activity of onconase targets cellular RNAs, in particular tRNA, with an accompanying inhibition of protein synthesis. In the present study, we have investigated the time- and dose-dependent effects of onconase on growth of Jurkat SN acute T-lymphocytic leukemia cells. Significant suppression of cell proliferation became evident after 72 and 96 h of treatment, and was most pronounced at the highest concentration (10 microg/ml; 8.3x10(-7) M) of onconase. This reduction of cell proliferation, however, was not accompanied by measurable changes in distribution of cells at different phases of the cell cycle, but was paralleled by the induction of apoptosis, as assayed by flow cytometry, and with a modest decrease in the expression of a cell cycle regulatory retinoblastoma protein (Rb). Further biochemical analysis revealed that growth suppression was closely coordinated with a down-regulation in the steady state and subcellular distribution of NF-kappaB, a transcription factor known to be functionally associated with cell survival. The reduction in expression of NF-kappaB by onconase appeared to coincide or even precede growth suppression, suggesting a causal relationship. To further test the hypothesis that cellular localization and expression of NF-kappaB may be critical to cellular response to onconase, we also studied the growth effects of onconase in Jurkat-BalphaM cells, which

  19. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  20. Chromosomal study for prognostic grouping in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Junaid, A.; Rao, P.N.

    2010-01-01

    To determine the frequency of various cytogenetic aberrations in newly diagnosed chronic lymphocytic leukemia (CLL) patients, and their detection rate by cytogenetic and fluorescent In situ hybridization (FISH) technique separately. Analysis was made on 100 diagnosed chronic lymphocytic leukemia patients. Cytogenetics and FISH technique were performed on blood or bone marrow samples. Nineteen out of 100 cases (19%) showed karyotype abnormalities; whereas 55 showed abnormalities using the CLL - specific FISH probes. The most frequent abnormality detected by standard cytogenetics was trisomy 12. The most common abnormality detected by FISH was a deletion of 13q14 (40 out of 55 cases; 72% of the abnormal). For prognostic grouping of CLL patients, FISH must always be requested which may even replace standard karyotyping. These chromosomal markers help in choosing the therapeutic options. (author)

  1. Fatal Cryptococcal Meningitis in a Patient With Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Oguzhan Sıtkı Dizdar

    2012-01-01

    Full Text Available

    Patients with chronic lymphocytic leukemia (CLL are susceptible to infections, especially opportunistic infections. We have described a patient with CLL who had cryptococcal meningitis. Despite lack of previous immunosuppressive treatment history, the patient experienced serious and fatal fungal infection. Physicians should be alert for a diagnosis of cryptococcal meningitis in patient with CLL who developed fever and headache.

  2. Genomic aberrations and survival in chronic lymphocytic leukemia.

    Science.gov (United States)

    Döhner, H; Stilgenbauer, S; Benner, A; Leupolt, E; Kröber, A; Bullinger, L; Döhner, K; Bentz, M; Lichter, P

    2000-12-28

    Fluorescence in situ hybridization has improved the detection of genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. Mononuclear cells from the blood of 325 patients with chronic lymphocytic leukemia were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of bands 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecular cytogenetic data were correlated with clinical findings. Chromosomal aberrations were detected in 268 of 325 cases (82 percent). The most frequent changes were a deletion in 13q (55 percent), a deletion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (7 percent). Five categories were defined with a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal karyotype, and 13q deletion as the sole abnormality; the median survival times for patients in these groups were 32, 79, 114, 111, and 133 months, respectively. Patients in the 17p- and 11q-deletion groups had more advanced disease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presence or absence of a 17p deletion, the presence or absence of an 11q deletion, age, Binet stage, the serum lactate dehydrogenase level, and the white-cell count gave significant prognostic information. Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.

  3. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  4. Outcomes in critically ill chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Xhaard, Aliénor; Epelboin, Loic; Schnell, David; Vincent, François; Levy, Vincent; Malphettes, Marion; Azoulay, Elie; Darmon, Michaël

    2013-07-01

    Although recent studies have demonstrated an improvement in the prognosis of critically ill cancer patients, little is known regarding the prognosis of patients with non-aggressive underlying malignancies. The aims of this study were to assess the prognosis of critically ill patients with chronic lymphocytic leukemia (CLL) and to evaluate risk factors for hospital mortality. In retrospective mono-center cohort study, consecutive adult patients with CLL requiring ICU admission from 1997 to 2008 were included. Sixty-two patients of 67 years (62-75) were included. Median time interval between CLL diagnosis and ICU admission was 6.7 years (2.6-10.8). Nine patients (15 %) had stage C disease at the time of ICU admission, and seven patients (11 %) had Richter syndrome. Most ICU admissions were related to bacterial or fungal pulmonary infections (n = 47; 76 %). ICU, in-hospital, and 90-day mortality were 35 % (n = 22), 42 % (n = 26), and 58 % (n = 36), respectively. Only three factors were independently associated with in-hospital mortality: oxygen saturation lower than 95 % when breathing room air (odds ratio (OR) 5.80; 95 % confidence interval (CI) 1.23-27.33), need for vasopressors (OR 27.94; 95 % CI 5.37-145.4), and past history of infection (OR 6.62; 95 % CI 1.34-32.68). The final model did not change when disease-related variables (Binet classification, Richter syndrome, long-term steroids) or treatment-related variables (fludarabine, rituximab, or alemtuzumab) were included. Acute pulmonary infections remain the leading cause of ICU admission in patients with CLL. The severity at ICU admission and past history of infection were the only factors associated with hospital mortality. Neither disease characteristics nor previous cancer treatments were associated with outcome.

  5. Acute Myelogenous Leukemia Mimicking Fulminant Periorbital Cellulitis

    Directory of Open Access Journals (Sweden)

    Abbas Bagheri

    2013-01-01

    Full Text Available Purpose: To report a patient who was referred for orbital cellulitis but was finally diagnosed with acute leukemia. Case Report: A 17-year-old boy presented with fever, periorbital erythema and swelling mimicking periorbital cellulitis. He underwent empiric antibiotic therapy. Complete blood counts revealed leukocytosis with a predominance of immature blast cells. Bone marrow aspiration confirmed the diagnosis of acute myelogenous leukemia. Chemotherapy was initiated resulting in resolution of signs and symptoms. Conclusion: Acute leukemia may mimic periorbital cellulitis and must be considered in the differential diagnosis.

  6. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  7. Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans.

    Science.gov (United States)

    Robin, Marie; Schlageter, Marie-Hélène; Chomienne, Christine; Padua, Rose-Ann

    2005-10-01

    Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.

  8. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2018-03-05

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  9. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    Science.gov (United States)

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

  10. Large Granular Lymphocytic Leukemia: A Report of Response to Rituximab

    Directory of Open Access Journals (Sweden)

    Uroosa Ibrahim

    2017-01-01

    Full Text Available Large granular lymphocytic (LGL leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months’ duration. A CBC showed that pancytopenia with an absolute neutrophil count (ANC was 0. Peripheral blood flow cytometry detected increased number of T cell large granular lymphocytes and T cell receptor rearrangement study detected a clonal T cell population. Bone marrow biopsy showed peripheral T cell lymphoma, most consistent with T-large granulocytic leukemia. The patient was treated with prednisone and oral cyclophosphamide for four months with no response. Thereafter, she received four weekly infusions of rituximab with improvement in her blood counts. A response to rituximab in refractory cases such as ours has been reported and may guide us towards exploring other immune-based therapeutics in this rare disease.

  11. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Olfa Kassar

    2015-01-01

    Full Text Available Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients.

  12. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Leonardo Rodrigues de Oliveira

    2013-09-01

    Full Text Available Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

  13. Protothecosis in a patient with T cell lymphocytic leukemia.

    Science.gov (United States)

    Fernández, Mariana S; Rojas, Florencia D; Cattana, María E; Mussin, Javier E; de Los Ángeles Sosa, María; Benzoni, Carlos D; Giusiano, Gustavo E

    Human protothecosis is a rare infection caused by algae of the genus Prototheca. Prototheca wickerhamii has been recognized as the main species that causes infection in immunocompromised hosts with deficits in innate or cellular immunity. We report a case of persisting subcutaneous protothecosis in a patient with T-cell large granular lymphocyte leukemia, who also presented a history of disseminated histoplasmosis. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    Science.gov (United States)

    2018-03-02

    Adult Acute Myeloid Leukemia in Remission; Acute Biphenotypic Leukemia; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Acute Myeloid Leukemia; Adult Acute Lymphoblastic Leukemia; Interleukin-3 Receptor Subunit Alpha Positive; Minimal Residual Disease; Refractory Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

    2016-04-01

    Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

  16. Lymphocytic Pleural Effusion in Acute Melioidosis

    Directory of Open Access Journals (Sweden)

    Kuo-Mou Chung

    2007-10-01

    Full Text Available An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.

  17. A novel human monoclonal antibody, TONO-1, reactive with T-lymphocytic leukemia cells.

    Science.gov (United States)

    Numasaki, M; Fukuoka, Y; Kudo, T; Saeki, H; Tachibana, T; Motomiya, M; Nukiwa, T

    1995-07-04

    Mononuclear cells from the peripheral blood of patients with systemic lupus erythematosus (SLE) were transformed with the Epstein-Barr virus (EBV) and the resultant polyclonal B-lymphoblastoid cell lines were tested for antibody activity to membrane antigens of certain T-cell lines. B lymphoblastoid cell lines secreting specific antibodies were fused with (mouse x human) heteromyeloma SHM-D33 cells. Among the large number of hybridomas generated, one which produced a human monoclonal antibody (MAb) TONO-1 (IgM, lambda) was selected. MAb TONO-1 proved to be reactive with 4 human T-cell lines, HPB-MLT, L-MAT, MOLT-3 and MOLT-4F, but not with B-leukemia, Burkitt's lymphoma, myelomonocytic leukemia, erythroleukemia or non-hematopoietic malignant cell lines. MAb TONO-1 reacted positively with fresh leukemia cells from 2 of 7 patients with acute T-lymphocytic leukemia, but no reaction was observed in non-T-cell leukemia cases. Normal lymphocytes, monocytes, granulocytes, red blood cells and platelets in the peripheral blood did not demonstrate remarkable binding. Neither thymocytes nor bone-marrow cells from healthy volunteers were reactive. The antigens defined by MAb TONO-1 were polypeptides of 57 kDa and 68 kDa. Immunohistological studies revealed no staining of thymocytes in the thymus of a 6-month-old child, but showed epithelial reticular cells and Hassall's corpuscles to stain positively. These results suggest that MAb TONO-1 is directed to T-leukemic cells and some components of thymus tissue.

  18. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

    NARCIS (Netherlands)

    T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

    2010-01-01

    textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

  19. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    Science.gov (United States)

    2018-01-24

    Acute Undifferentiated Leukemia; 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); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Benzene and childhood acute leukemia in Oklahoma.

    Science.gov (United States)

    Janitz, Amanda E; Campbell, Janis E; Magzamen, Sheryl; Pate, Anne; Stoner, Julie A; Peck, Jennifer D

    2017-10-01

    Although childhood cancer is a leading cause of childhood mortality in the US, evidence regarding the etiology is lacking. The goal of this study was to evaluate the association between benzene, a known carcinogen, and childhood acute leukemia. We conducted a case-control study including cases diagnosed with acute leukemia between 1997 and 2012 (n = 307) from the Oklahoma Central Cancer Registry and controls matched on week of birth from birth certificates (n = 1013). We used conditional logistic regression to evaluate the association between benzene, measured with the 2005 National-Scale Air Toxics Assessment (NATA) at census tract of the birth residence, and childhood acute leukemia. We observed no differences in benzene exposure overall between cases and controls. However, when stratified by year of birth, cases born from 2005 to 2010 had a three-fold increased unadjusted odds of elevated exposure compared to controls born in this same time period (4th Quartile OR: 3.53, 95% CI: 1.35, 9.27). Furthermore, the estimates for children with acute myeloid leukemia (AML) were stronger than those with acute lymphoid leukemia, though not statistically significant. While we did not observe an association between benzene and childhood leukemia overall, our results suggest that acute leukemia is associated with increased benzene exposure among more recent births, and children with AML may have increased benzene exposure at birth. Using the NATA estimates allowed us to assess a specific pollutant at the census tract level, providing an advantage over monitor or point source data. Our study, however, cannot rule out the possibility that benzene may be a marker of other traffic-related exposures and temporal misclassification may explain the lack of an association among earlier births. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Thrombosis in adult patients with acute leukemia.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Del Principe, Domenico; Venditti, Adriano

    2017-11-01

    Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA. Furthermore, leukemic blasts can activate the procoagulant population of platelets, which initiate and amplify coagulation, causing thrombosis. In addition to factors produced by acute leukemia itself, others concur to trigger thrombosis. Some drugs, infections and insertion of central venous catheter have been described to increase risk of thrombosis in patients with acute leukemia. Thrombosis represents a serious complication in patients affected by myeloid and lymphoid acute leukemia. A proper knowledge of its pathophysiology and of the predisposing risk factors may allow to implement strategies of prevention. Improving prevention of thrombosis appears a major goal in patients whose frequent conditions of thrombocytopenia impede an adequate delivery of anticoagulant therapy.

  2. Nucleophosmin 1 expression in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Mohammad Davoudi

    2015-09-01

    Full Text Available Nucleophosmin1 is a multifunctional protein that shuttles between nucleus and cytoplasm in some subtypes of acute myeloid leukemias. Mutated Nucleophosmin1 expresses aberrantly in the cytoplasm of the cell and transports from nucleolus to the cytoplasm. It is diagnosed by immunohistochemical techniques, flow cytometry assay and mutational analysis.The aim of this study is to evaluate the effects of Nucleophosmin1 mutation on the clinical presentations, prognosis, diagnosis and the treatment of acute myeloid leukemia. Thirteen articles were extracted from PubMed, Google scholar and Scopus in which the Nucleophosmin1 mutation correlated with gingival hyperplasia, high white blood cell count, lymphadenopathy, high platelet count and other signs and symptoms of myelomonocytic and monocytic acute myeloid leukemias. This mutation is a provisional entity in the classification of acute myeloid leukemia, which influences on the prognosis, clinical course and the treatment of some subtypes of acute myeloid leukemias. Nucleophosmin1 mutation has favorable prognostic value in the absence of other concomitant mutations.

  3. [Effect of CDK Inhibitor LS-007 on Acute Lymphoblastic Leukemia and Its Mechanism].

    Science.gov (United States)

    Lu, Jiang-Feng; Xu, Feng-Ling; Lu, Jun; Ren, Yu-Guo

    2017-04-01

    To study the effect of cyclin dependent kinase(CDK) inhibitor LS-007 on acute lymphoblastic leukemia and its mechanism. The acute lymphocytic leukemia cell line was cultured and treated by LS-007, flavopiridol and ABT-199, then the changes of apoptosis-related factor mRNA and protein levels were detected by using mRNA quantitative PCR and Werstern blot. quantitative PCR and Western blot detection showed that the levels of antiapoptotic protein decreased significantly in acute lymphoblastic leukemia cells after LS-007 treatment, and the pro-apoptotic effect of LS-007 combined with ABT-199 was much better. LS-007 can affect the phosphorylation of RNA polymerase sites and promote cell apoptosis through changing the activities of CDK, thus having some positive significance for relieving acute lymphoblastic leukemia.

  4. A case of chronic lymphocytic leukemia with massive ascites

    Directory of Open Access Journals (Sweden)

    Meliha Nalcaci

    2012-10-01

    Full Text Available An 81-year old woman with a history of chronic lymphocytic leukemia (CLL was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC count 28.5x109/L and platelets 38.4x109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely gran- ular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites.

  5. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    Science.gov (United States)

    2018-03-19

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  6. Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants

    Science.gov (United States)

    Agathanggelou, Angelo; Weston, Victoria J.; Perry, Tracey; Davies, Nicholas J.; Skowronska, Anna; Payne, Daniel T.; Fossey, John S.; Oldreive, Ceri E.; Wei, Wenbin; Pratt, Guy; Parry, Helen; Oscier, David; Coles, Steve J.; Hole, Paul S.; Darley, Richard L.; McMahon, Michael; Hayes, John D.; Moss, Paul; Stewart, Grant S.; Taylor, A. Malcolm R.; Stankovic, Tatjana

    2015-01-01

    Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumors with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia. PMID:25840602

  7. Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

    Science.gov (United States)

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

  8. Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

    1981-01-01

    Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

  9. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    International Nuclear Information System (INIS)

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC 1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

  10. Aspergillus vegetative endocarditis and complete heart block in a patient with acute leukemia.

    Science.gov (United States)

    Mikulski, S M; Love, L J; Bergquist, E J; Hargadon, M T; Applefeld, M M; Mergner, W

    1979-10-01

    Aspergillus flavus vegetative endocarditis together with myocardial abscesses and pneumonitis developed in a patient with acute lymphocytic leukemia. The initial diagnosis was not suspected until 67gallium imaging revealed a radiographically undetectable thoracic abnormality. Despite apparently "early" diagnosis, antifungal therapy was inadequate to prevent disruption of the bundle of His, complete heart block and death.

  11. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  12. REGULATORY T-CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Giovanni D'arena

    2012-08-01

    Full Text Available Regulatory T-cells (Tregs constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL. Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosis, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in either cancer and autoimmune disorders.

  13. A lapachol derivative active against mouse lymphocytic leukemia P-388.

    Science.gov (United States)

    da Consolação, M; Linardi, F; de Oliveira, M M; Sampaio, M R

    1975-11-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] and its analogs [2-(3,7-dimethyl-2,6-octadienyl)-3-hydroxy-1,4-naphthoquinone and 2-(3,3-dibromo-2-propenyl)-3-hydroxy-1,4-naphthoquinone] have been described, among almost a hundred synthesized analogs, as active against rat tumor Walker 256 carcinosarcoma. The acetylglucosylation of lapachol results in a compound which extends lapachol activity becoming effective against mouse lymphocytic leukemia P-388. When mice inoculated with 10(6) leukemic cells were treated with the drug during 9 days, their life span increased 80% over the control animals. Identification spectral data (uv, ir, 1H NMR, and MS) of the compound obtained by synthesis are given.

  14. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    Science.gov (United States)

    2018-03-26

    HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  15. Cranial irradiation in acute leukemia: dose estimate in the lens

    International Nuclear Information System (INIS)

    Kline, R.W.; Gillin, M.T.; Kun, L.E.

    1979-01-01

    Cranial irradiation for subclinical arachnoid infiltration is standard treatment in childhood acute lymphocytic leukemia. The incidental dose received by the ocular lens is of potential importance since these children evidence a significant long-term survival rate. Comparison of the lens dose using 6MV and 4MV photon beams and a cobalt unit is presented in terms of ion chamber measurements in a water phantom and thermo-luminescent dosimetry (TLD) measurements in a head phantom. TLD measurements on patients treated for acute lymphocytic leukemia (ALL) are examined and used to estimate the dose to the lens. It is demonstrated that the dose to the lens depends strongly on the choice of field margin and on the daily patient set-up. However, using parallel opposed beams in a clinically determined optimal set-up, the dose to the lens is approximately 20 to 30% of the midline central axis dose. By angling the treatment head to eliminate the geometrical divergence of the beam, it is possible to reduce the lens dose to approximately 15% of the midline dose

  16. Overview of recent developments in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Preetesh Jain

    2012-01-01

    Full Text Available Multiple advances have been made in our understanding of pathobiology of chronic lymphocytic leukemia (CLL. These developments in the laboratory include new prognostic markers, risk stratification of the disease and newer therapeutic agents in CLL. These advances in CLL have come a long way in the past three decades since the development of Rai and Binet clinical staging systems. Important strides in the pathobiology, from defining mutational status of IGHV, to B-cell receptor (BCR signaling pathways and CLL microenvironment have made a major difference in our understanding of this disease. Mutational status of immunoglobulin heavy chain genes (IGHV, CD38 and Zap-70, chromosomal aberrations and newer mutations, are the most clinically relevant prognostic markers. Chemoimmunotherapy (CIT has become the treatment of choice for young and fit CLL patients. Various inhibitors of BCR signaling pathways and immunomodulatory drugs have shown efficacy in clinical trials. The most recent advance is the use of chimeric antigen receptor therapy (CAR based on autologous T-lymphocytes. Nevertheless, CLL remains an incurable disease today. Coordinated developments between laboratory and clinic will hopefully translate into a cure for CLL. This short review focuses on advances in prognostication and therapy in CLL.

  17. A rare case of chronic lymphocytic leukemia/small lymphocytic lymphoma presenting in the thyroid gland.

    Science.gov (United States)

    Shin, Joyce; Chute, Deborah; Milas, Mira; Mitchell, Jamie; Siperstein, Allan; Berber, Eren

    2010-09-01

    Lymphoma involving the thyroid gland is rare. Diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma are the two most common histologic subtypes of primary thyroid lymphoma. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presenting initially as a thyroid abnormality is extremely rare, with very few reported cases in the literature. We report a case of a patient with a long history of Hashimoto's thyroiditis and goiter who presented with a recent enlargement of her thyroid gland. The sonographic finding of a distinct thyroid nodule in the heterogeneous background of chronic lymphocytic thyroiditis led to the performance of a fine-needle aspiration biopsy and flow cytometry, with a high index of suspicion for thyroid lymphoma. Subsequent surgical removal of the thyroid gland, prompted by the patient's history of head and neck radiation, confirmed the diagnosis of CLL/SLL. The patient's systemic illness was recognized only after the management of her thyroid disease. Although thyroiditis has long been associated with lymphoma arising in the thyroid gland, CLL/SLL involving the thyroid has not been linked to chronic lymphocytic thyroiditis. Therefore, the patient also had coexisting thyroiditis. Due to the rarity of thyroid lymphomas, our experience in the detection and management of this disease is limited. Primary thyroid lymphoma should be suspected in a patient with a history of chronic lymphocytic thyroiditis presenting with a rapidly enlarging neck mass. The initial diagnostic method for thyroid lymphoma should consist of a fine-needle aspiration biopsy with the use of ancillary techniques such as flow cytometry and immunohistochemistry for improved diagnostic accuracy. Although controversial, the treatment of thyroid lymphoma is typically guided by the histologic subtype and extent of disease. CLL/SLL is one of the rarest subtypes of lymphoma that can involve the thyroid gland. Diagnosis of this entity is difficult

  18. Total body irradiation for allogeneic bone marrow transplantation in acute leukemia: A cooperative study from the TBI Subcommittee in Japan

    International Nuclear Information System (INIS)

    Inoue, T.; Masaoka, T.; Shibata, H.

    1986-01-01

    By means of national survey, records of 78 acute leukemia patients who underwent allogeneic bone marrow transplantation (BMT) from September 1975 through September 1983 were collected from 14 participating institutions in Total Body Irradiation (TBI) Subcommittee in Japan. Patients were classified into 37 of acute lymphocytic leukemia (ALL), and 41 of acute non-lymphocytic leukemia (ANLL). One-year survivals were 51% and 33% in ALL and ANLL patients, respectively. Uninfected patients in remission had significantly better survival than infected ones and/or in relapse. Overall incidence of interstitial pneumonia was 43%. Rejection and relapse were encountered in 26% of patients. Concerning cause of death, interstitial pneumonia was the most frequent cause (44%). Uni- and multivariate analyses strongly suggested that favorable prognostic factors were remission, uninfection, preparation of low-dose-rate fractionated TBI and cyclophosphamide, and mild graft-versus-host disease (GVHD) for acute leukemia patient treated with allogeneic BMT. (orig.) [de

  19. Evidence for the replication of bovine leukemia virus in the B lymphocytes

    International Nuclear Information System (INIS)

    Paul, P.S.; Pomeroy, K.A.; Johnson, D.W.; Muscoplat, C.C.; Handwerger, B.S.; Soper, F.F.; Sorensen, D.K.

    1977-01-01

    Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells

  20. Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-04

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

    Han Li-na, [No Value; Zhou Jin, [No Value; Schuringa, Jan Jacob; Vellenga, Edo

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials. Data sources The data in this article were collected from PubMed database with relevant

  2. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    OpenAIRE

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2014-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene.

  3. CYTOGENETIC ANALYSIS IN SLOVENIAN ACUTE LEUKEMIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Helena Podgornik

    2008-04-01

    Using molecular cytogenetic and genetic methods a possibility that some of chromosomalchanges were overlooked was considerably minimized. On the basis of the analyzed datawe can be confident that the cytogenetic diagnostic approach in our acute leukemia patients is in accordance with international guidelines

  4. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Having a child with cancer can make you feel very alone. In a cancer support group, you can find people who are going ... Updated July 28, 2016. National Cancer Institute. www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq . Accessed August 3, 2016. Wei ...

  5. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death

    DEFF Research Database (Denmark)

    Andersen, Michael Asger; Vojdeman, Fie Juhl; Andersen, Mette Klarskov

    2016-01-01

    Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment-free survi...

  6. The MLL recombinome of acute leukemias in 2013

    DEFF Research Database (Denmark)

    Meyer, C; Hofmann, Julian; Burmeister, T

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia ...

  7. 3D protein-structure-oriented discovery of clinical relation across chronic lymphocytic leukemia patients

    DEFF Research Database (Denmark)

    Mochament, Konstantinos; Agathangelidis, Andreas; Polychronidou, Eleftheria

    2017-01-01

    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with still unclear etiology. Indications of antigenic pressure have been hinted, using sequence and structure-based reasoning. The accuracy of such approaches, and in particular of the ones derived from 3D models obtained from t...

  8. CLINICAL AND IMMUNO-METABOLIC PECULIARITIES OF THE PRIMARY ATTACK OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Olga Valentinovna Smirnova

    2017-12-01

    Full Text Available The authors studied the characteristics of the clinical condition, cellular, humoral immunity and metabolism of lymphocytes in patients with acute lymphoblastic leukemia at the onset of the disease, with the primary attack. The disease usually begins with the combined symptoms appearance in the clinical picture. Fever, fatigue, decreased performance, dizziness, the accompanying infection process were recorded in most patients. Reduction of T-lymphocytes and a decrease in the ratio of CD4+ to CD8+ contributed to the debut appearance of ALL and T-cell immunodeficiency development. Changed metabolomics of energy, plastic processes in lymphocytes. The authors proposed an immunometabolic own concept of the disease.

  9. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.

    Science.gov (United States)

    Salimi, Ahmad; Motallebi, Abbasali; Ayatollahi, Maryam; Seydi, Enayatollah; Mohseni, Ali Reza; Nazemi, Melika; Pourahmad, Jalal

    2017-04-01

    Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5 + B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017. © 2016 Wiley Periodicals, Inc.

  11. Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ceren Günel

    2015-04-01

    Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

  12. Targeting MTHFD2 in acute myeloid leukemia.

    Science.gov (United States)

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M; Frumm, Stacey M; Ross, Linda; Fenouille, Nina; Bassil, Christopher F; Lewis, Caroline A; Ramos, Azucena; Gould, Joshua; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene; Clish, Clary B; Kung, Andrew L; Hemann, Michael T; Vander Heiden, Matthew G; Banerji, Versha; Stegmaier, Kimberly

    2016-06-27

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. © 2016 Pikman et al.

  13. THERAPY-RELATED MYELOID NEOPLASMS IN CHRONIC LYMPHOCYTIC LEUKEMIA AND WALDENSTROM MICROGLOBULINEMIA

    Directory of Open Access Journals (Sweden)

    Francesca Ricci

    2011-07-01

    Full Text Available Secondary myelodisplasia (MDS and acute myeloide leukaemia (AML are frequent long term complications in Chronic Lymphocytic Leukemia (CLL and Waldesntrom Macroglobulinemia (WM patients. Although disease-related immune-suppression plays a crucial role in leukemogenesis there is great concern that therapy may further increase the risk of developing these devastating complications. Nucleoside analogs (NA and alkilator agents are considered appropriate agents in the treatment of both CLL and WM patients. Prolonged immunosuppression related to nucleoside analogs therapy and the incorporation of these agents or their metabolites into DNA, with potentially mutagenic action, leads to speculation that their therapeutic use might be responsible for an increased incidence of second cancer especially when combined with other DNA damaging agents like alkylators. In this review the published studies considering the occurrence of secondary MDS and AML in CLL and WM patients are reported and the potential role of chemotherapeutic agents in leukemogenesis is discussed.

  14. Norovirus-related chronic diarrhea in a patient treated with alemtuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Ronchetti, Anne-Marie; Henry, Benoit; Ambert-Balay, Katia; Pothier, Pierre; Decroocq, Justine; Leblond, Véronique; Roos-Weil, Damien

    2014-05-06

    Norovirus infection is increasingly recognized as an important cause of persistent gastroenteritis in immunocompromised hosts and can be a potential cause of morbidity in these populations. Here, we report a case of norovirus-related chronic diarrhea occurring in a 62-year-old immunocompromised patient treated with alemtuzumab for chronic lymphocytic leukemia. Despite different therapeutic strategies including tapering of immunosuppressive therapy and immunoglobulin administration, diarrhea unfortunately did not resolve and lasted for a total of more than twelve weeks with prolonged norovirus fecal excretion. Norovirus infection can occur in the setting of alemtuzumab treatment, even as a single agent, and should be included in the differential diagnoses of acute and chronic diarrhea in these immunocompromised patients. Although the administration of oral immunoglobulin has been described as a promising efficient therapy, this was not the case in our patient. Clinical trials are thus clearly warranted to better define risk factors and efficient therapies for norovirus infection in immunocompromised populations.

  15. AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

    Directory of Open Access Journals (Sweden)

    Pavankumar Tandra

    2013-11-01

    Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

  16. TACI Expression and Signaling in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Antigoni Mamara

    2015-01-01

    Full Text Available TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL, including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.

  17. Large granular lymphocyte leukemia: natural history and response to treatment.

    LENUS (Irish Health Repository)

    Fortune, Anne F

    2012-02-01

    Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and\\/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.

  18. [Chronic lymphocytic leukemia. Treatment and genetic risk profile].

    Science.gov (United States)

    Stilgenbauer, S; Hallek, M

    2013-02-01

    Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Among the biological features underlying this heterogeneity, genetic lesions and the mutational status of the immunoglobulin heavy chain variable genes (IGHV) are of importance. Therapeutic options in CLL have been considerably expanded during recent years. The combination of fludarabine, cyclophosphamide and rituximab (FCR) has become gold standard in the first-line treatment of physically fit patients. Bendamustine plus rituximab (BR) is currently being compared to FCR in studies and chlorambucil is still of relevance for elderly patients with comorbidities. Alemtuzumab is an alternative for high-risk patients (refractory CLL, 17p deletion, TP53 mutation). Allogeneic stem cell transplantation (allo-SCT) offers the only chance of cure but not without substantial mortality. Innovative approaches focus on individualized, targeted therapies. A number of novel agents are in clinical trials and show marked efficacy combined with good tolerability. This review provides an overview of the current therapeutic options and of promising novel approaches.

  19. Quantitative analysis of DNA methylation in chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Lyko, Frank; Stach, Dirk; Brenner, Axel; Stilgenbauer, Stephan; Döhner, Hartmut; Wirtz, Michaela; Wiessler, Manfred; Schmitz, Oliver J

    2004-06-01

    Changes in the genomic DNA methylation level have been found to be closely associated with tumorigenesis. In order to analyze the relation of aberrant DNA methylation to clinical and biological risk factors, we have determined the cytosine methylation level of 81 patients diagnosed with chronic lymphocytic leukemia (CLL). The analysis was based on DNA hydrolysis followed by derivatization of the 2'-desoxyribonucleoside-3'-monophosphates with BODIPY FL EDA. Derivatives were separated by micellar electrokinetic chromatography, and laser-induced fluorescence was used for detection. We analyzed potential correlations between DNA methylation levels and numerous patient parameters, including clinical observations and biological data. As a result, we observed a significant correlation with the immunoglobulin variable heavy chain gene (VH) mutation status. This factor has been repeatedly proposed as a reliable prognostic marker for CLL, which suggests that the methylation level might be a valuable factor in determining the prognostic outcome of CLL. We are now in the process of refining our method to broaden its application potential. In this context, we show here that the oxidation of the fluorescence marker in the samples and the evaporation of methanol in the electrolytes can be prevented by a film of paraffin oil. In summary, our results thus establish capillary electrophoresis as a valuable tool for analyzing the DNA methylation status of clinical samples.

  20. REGULATORY T-CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Giovanni D'arena

    2012-01-01

    Full Text Available

    Regulatory T-cells (Tregs constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL. Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosis, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in either cancer and autoimmune disorders.

  1. Genetic differences between Asian and Caucasian chronic lymphocytic leukemia

    Science.gov (United States)

    KAWAMATA, NORIHIKO; MOREILHON, CHIMENE; SAITOH, TAKAYUKI; KARASAWA, MASAMITSU; BERNSTEIN, BRIAN K.; SATO-OTSUBO, AIKO; OGAWA, SEISHI; RAYNAUD, SOPHIE; KOEFFLER, H. PHILLIP

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a common hematological malignancy in Western countries. However, this disease is very rare in Asian countries. It is not clear whether the mechanisms of development of CLL in Caucasians and Asians are the same. We compared genetic abnormalities in Asian and Caucasian CLL using 250k GeneChip arrays. Both Asian and Caucasian CLL had four common genetic abnormalities: deletion of 13q14.3, trisomy 12, abnormalities of ATM (11q) and abnormalities of 17p. Interestingly, trisomy 12 and deletion of 13q14.3 were mutually exclusive in both groups. We also found that deletions of miR 34b/34c (11q), caspase 1/4/5 (11q), Rb1 (13q) and DLC1 (8p) are common in both ethnic groups. Asian CLL more frequently had gain of 3q and 18q. These suggest that classic genomic changes in the Asian and Caucasina CLL are same. Further, we found amplification of IRF4 and deletion of the SP140/SP100 genes; these genes have been reported as CLL-associated genes by previous genome-wide-association study. We have found classic genomic abnormalities in Asian CLL as well as novel genomic alteration in CLL. PMID:23708256

  2. Study of splenic irradiation in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Guiney, M.J.; Liew, K.H.; Quong, G.G.; Cooper, I.A.

    1989-01-01

    A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population

  3. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  4. Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia.

    Science.gov (United States)

    Biancotto, Angélique; Dagur, Pradeep K; Fuchs, John C; Wiestner, Adrian; Bagwell, C Bruce; McCoy, J Philip

    2012-02-01

    Increased numbers of T regulatory (T(reg)) cells are found in B-chronic lymphocytic leukemia, but the nature and function of these T(regs) remains unclear. Detailed characterization of the T(regs) in chronic lymphocytic leukemia has not been performed and the degree of heterogeneity of among these cells has not been studied to date. Using 15-color flow cytometry we show that T(reg) cells, defined using CD4, CD25, and forkhead box P3 (FOXP3), can be divided into multiple complex subsets based on markers used for naïve, memory, and effector delineation as well as markers of T(reg) activation. Furthermore FOXP3(+) cells can be identified among CD4(+)CD25(-) as well as CD8(+)CD4(-) populations in increased proportions in patients with chronic lymphocytic leukemia compared with healthy donors. Significantly different frequencies of naïve and effector T(regs) populations are found in healthy donor controls compared with donors with chronic lymphocytic leukemia. A population of CCR7(+)CD39(+) T(regs) was significantly associated with chronic lymphocytic leukemia. This population demonstrated slightly reduced suppressive activity compared with total T(regs) or T(regs) of healthy donors. These data suggest that FOXP3-expressing cells, particularly in patients with chronic lymphocytic leukemia are much more complex for T(reg) sub-populations and transitions than previously reported. These findings demonstrate the complexity of regulation of T-cell responses in chronic lymphocytic leukemia and illustrate the use of high-dimensional analysis of cellular phenotypes in facilitating understanding of the intricacies of cellular immune responses and their dysregulation in cancer.

  5. Expression of CD133 in acute leukemia.

    Science.gov (United States)

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

  6. Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-16

    NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD...Profoosionaf 7 ,0 Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia Brittany Lenz, MD, Arturo Dominguez, MD, Adnan Mir, MD, PhD Objectives...with pre-B cell acute lymphoblastic leukemia was admitted for presumed septic shock secondary to an unknown infectious etiology. The patient was

  7. Prognosis and complications of acute childhood leukemia after prophylactic treatment of the central nervous

    International Nuclear Information System (INIS)

    Hosoki, Takuno; Harada, Koshi; Ikeda, Hiro; Miyata, Toshiaki; Kawai, Ryuji.

    1980-01-01

    From 1970 through 1979, 22 children with acute childhood leukemia and in remimmion were treated with preventive central nervous system (CNS) irradiation and simultaneous intrathecal methotrexate. A minimum follow-up duration was five months. Of 22 cases, 20 were acute lymphocytic leukemia (ALL) and 2 were acute myelocytic leukemia (ALL). Five-year cumulative survival rate and five-year relapse free survival rate of ALL case were 48% and 46% respectively. Nor neurological disorders after the prophylactic combined therapy were recognized clinically by the time when this follow-up was finished. Of 15 children with ALL who were followed by computed tomography of the brain, 5(33%) had abnormal findings. Dilatation of the ventricles were seen in 3 cases, and low density areas of the occipital regions in 2 cases. (author)

  8. Surrogate marker profiles for genetic lesions in acute leukemias.

    Science.gov (United States)

    Paietta, Elisabeth

    2010-09-01

    The basic hypothesis of surrogate marker profiles is that individual genetic lesions result in characteristic distortions of the cellular phenotype with some predictable consistency that can be exploited by sophisticated immunophenotyping. While cytogenetic and molecular aberrancies currently are accepted prognostic predictors in acute leukemias, single antigen expression and even antigenic profiles rarely impact on prognosis. However, increasingly, phenotypes are delineated which can serve as surrogates for underlying genetic aberrations of clinical importance. This development is of particular significance as antileukemic therapy becomes available that targets any component of the disturbed molecular pathways associated with these genetic lesions. This chapter will focus on established surrogate marker profiles, such as those for PML/RARα, AML1/ETO, FLT3-gene mutated acute lymphocytic leukemia (ALL), and BCR/ABL(POS) ALL. As the list of therapeutic targets grows, the role of surrogate antigen profiles will grow, as they can predict for the efficacy of targeted approaches in lieu of expensive, time-consuming and not always accessible genetic analyses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Lehmann, Sören; Ogawa, Seishi; Raynaud, Sophie D; Sanada, Masashi; Nannya, Yasuhito; Ticchioni, Michel; Bastard, Christian; Kawamata, Norihiko; Koeffler, H Phillip

    2008-03-15

    To the authors' knowledge, genetic abnormalities in early-stage chronic lymphocytic leukemia (CLL) have not been examined fully. Single nucleotide polymorphism (SNP) genomic array (SNP-chip) is a new tool that can detect copy number changes and uniparental disomy (UPD) over the entire genome with very high resolution. The authors performed SNP-chip analysis on 56 samples from patients with early-stage, untreated CLL. To validate the SNP-chip data, fluorescence in situ hybridization (FISH) analysis was performed at selected sites. Expression levels of ZAP-70 and the mutational status of immunoglobulin heavy-chain gene also were examined. SNP-chip analysis easily detected nearly all changes that were identified by FISH, including trisomy 12, deletion of TP53 (17p13), deletion of ATM (11q22), and deletion of 13q14. Only 10 of 56 CLL samples (18%) had no genomic abnormalities. Excluding the 4 common abnormalities mentioned above, 25 CLL samples (45%) had a total of 45 copy number changes detected by SNP-chip analysis. Four samples had 6q deletion at 6q21 that involved the AIM1 gene. UPD was detected in 4 samples; 2 samples involved whole chromosome 13 resulting in homozygous deletion of micro-RNA-15a (miR-15a)/miR-16-1. CLL samples with deletion of 13q14 and trisomy 12 were mutually exclusive. Genetic abnormalities, including whole chromosome 13 UPD, are very common events in early-stage CLL. SNP-chip analysis can detect small genetic abnormalities in CLL and may be able to support or even supplant FISH and cytogenetics. Copyright (c) 2008 American Cancer Society.

  11. Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells

    NARCIS (Netherlands)

    Baou, Maria; Kohlhaas, Susan L.; Butterworth, Michael; Vogler, Meike; Dinsdale, David; Walewska, Renata; Majid, Aneela; Eldering, Eric; Dyer, Martin J. S.; Cohen, Gerald M.

    2010-01-01

    Bortezomib has been successfully used in the treatment of multiple myeloma and has been proposed as a potential treatment for chronic lymphocytic leukemia. In this study we investigated the mechanism by which bortezomib induces apoptosis in chronic lymphocytic leukemia cells. Using western blot

  12. Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells

    NARCIS (Netherlands)

    Baou, M.; Kohlhaas, S.L.; Butterworth, M.; Vogler, M.; Dinsdale, D.; Walewska, R.; Majid, A.; Eldering, E.; Dyer, M.J.S.; Cohen, G.M.

    2010-01-01

    Background Bortezomib has been successfully used in the treatment of multiple myeloma and has been proposed as a potential treatment for chronic lymphocytic leukemia. In this study we investigated the mechanism by which bortezomib induces apoptosis in chronic lymphocytic leukemia cells. Design and

  13. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    International Nuclear Information System (INIS)

    Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula

    2009-01-01

    Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance

  14. The MLL recombinome of acute leukemias in 2017

    DEFF Research Database (Denmark)

    Meyer, C; Burmeister, T; Gröger, D

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs)...

  15. Acute myeloid leukemia: advances in diagnosis and classification.

    Science.gov (United States)

    Hasserjian, R P

    2013-06-01

    Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans. © 2013 Blackwell Publishing Ltd.

  16. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Sabina Chiaretti

    2014-10-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly in function of ALL subset, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review offers a glimpse on how best identify ALL and the most relevant ALL subsets.

  17. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  18. Epigenetic analysis of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Dunwell, Thomas L; Hesson, Luke B; Pavlova, Tatiana; Zabarovska, Veronika; Kashuba, Vladimir; Catchpoole, Daniel; Chiaramonte, Raffaella; Brini, Anna T; Griffiths, Mike; Maher, Eamonn R; Zabarovsky, Eugene; Latif, Farida

    2009-04-01

    We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B", alpha) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, beta) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2'-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.

  19. Update in the management of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lin Thomas S

    2009-07-01

    Full Text Available Abstract Advances in the treatment of chronic lymphocytic leukemia (CLL have improved initial overall response (OR rates, complete response (CR rates and progression free survival (PFS. Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22 and del(17p13. The 2008 American Society of Hematology (ASH Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophosphamide (FCR significantly improved OR, CR and PFS. The improvement in PFS directly resulted from an improved ability to eliminate minimal residual disease (MRD in the peripheral blood, highlighting the importance of MRD eradication. However, a multi-center study suggested that the high CR rates to chemoimmunotherapy regimens such as FCR obtained in academic centers may not be reproducible when the same regimens are given in the community setting. The immunomodulatory drug lenalidomide is active in relapsed high-risk CLL, but two studies of lenalidomide in previously untreated CLL patients failed to achieve a CR and were associated with significant tumor lysis, tumor flare and hematologic toxicity. In the relapsed setting, a combination study of the bifunctional alkylator bendamustine and rituximab (BR demonstrated a high OR rate in patients with del(11q22 and del(17p13, indicating that further studies to define's bendamustine activity are warranted in high-risk CLL. Similarly, the CDK inhibitor flavopiridol demonstrated significant clinical activity and durable remissions in heavily treated, refractory CLL patients with high-risk cytogenetic features and bulky

  20. [Leukemia research in Germany: the Competence Network Acute and Chronic Leukemias].

    Science.gov (United States)

    Kossak-Roth, Ute; Saußele, Susanne; Aul, Carlo; Büchner, Thomas; Döhner, Hartmut; Dugas, Martin; Ehninger, Gerhard; Ganser, Arnold; Giagounidis, Aristoteles; Gökbuget, Nicola; Griesshammer, Martin; Hasford, Jörg; Heuser, Michael; Hiddemann, Wolfgang; Hochhaus, Andreas; Hoelzer, Dieter; Niederwieser, Dietger; Reiter, Andreas; Röllig, Christoph; Hehlmann, Rüdiger

    2016-04-01

    The Competence Network "Acute and Chronic Leukemias" was founded in 1997 by the consolidation of the leading leukemia study groups in Germany. Key results are the development of new trials and cooperative studies, the setup of patient registries and biobanking facilities, as well as the improvement of study infrastructure. In 2003, the concept of the competence network contributed to the foundation of the European LeukemiaNet (ELN). Synergy with the ELN resulted in cooperation on a European and international level, standardization of diagnostics and treatment, and recommendations for each leukemia and interdisciplinary specialty. The ultimate goal of the network is the cure of leukemia through cooperative research.

  1. Cell surface antigens of radiation leukemia virus-induced BALB/c leukemias defined by syngeneic cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Kaneko, Yukio; Oettgen, H.F.; Obata, Yuichi; Nakayama, Eiichi.

    1989-01-01

    Two cell surface antigens of mouse leukemias were defined by BALB/c cytotoxic T lymphocytes (CTL) generated against syngeneic radiation leukemia virus (RadLV)-induced leukemia, BALBRV1 or BALBRVD. Hyperimmunization of BALB/c mice with irradiated leukemias followed by in vitro sensitization of primed spleen cells resulted in the generation of CTL with high killing activity. The specificity of CTL was examined by direct cytotoxicity assays and competitive inhibition assays. A shared cell surface antigen, designated as BALBRV1 antigen, was detected by BALB/c anti-BALBRV1 CTL. BALBRV1 antigen was expressed not only on RadLV-induced BALB/c leukemias except for BALBRVD, but also on spontaneous or X-ray-induced BALB/c leukemias, chemically-induced leukemias with the H-2 d haplotype and some chemically-induced BALB/c sarcomas. In contrast, a unique cell surface antigen, designated as BALBRVD antigen, was detected by BALB/c anti-BALBRVD CTL. BALBRVD antigen was expressed only on BALBRVD, but not on thirty-nine normal lymphoid or tumor cells. These two antigens could be distinguished from those previously defined on Friend, Moloney, Rauscher or Gross murine leukemia virus (MuLV) leukemias, or MuLV-related antigens. Both cytotoxic responses were blocked by antisera against H-2K d , but not H-2D d . The relationship of BALBRV1 antigen and BALBRVD antigen to endogenous MuLV is discussed with regard to the antigenic distribution on tumor cell lines. (author)

  2. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-AL...

  3. Cell size variations of large granular lymphocyte leukemia: Implication of a small cell subtype of granular lymphocyte leukemia with STAT3 mutations.

    Science.gov (United States)

    Tanahashi, Takahiro; Sekiguchi, Nodoka; Matsuda, Kazuyuki; Takezawa, Yuka; Ito, Toshiro; Kobayashi, Hikaru; Ichikawa, Naoaki; Nishina, Sayaka; Senoo, Noriko; Sakai, Hitoshi; Nakazawa, Hideyuki; Ishida, Fumihiro

    2016-06-01

    Large granular lymphocyte leukemia (LGL-L) has been morphologically defined as a group of lymphoproliferative disorders, including T-cell large granular lymphocytic leukemia (T-LGL-L), chronic lymphoproliferative disorders of NK cells (CLPD-NK) and aggressive NK cell leukemia. We investigated the morphological features of LGL leukemic cells in 26 LGL-L patients in order to elucidate relationships with current classifications and molecular backgrounds. LGL-L cells were mostly indistinguishable from normal LGL. Patients with STAT3 SH2 domain mutations showed significantly smaller cells compared with patients without STAT3 mutations. Four patients with T-LGL-L showed smaller granular lymphocytes with a median diameter of less than 13μm, which were rarely seen in normal subjects. This small subtype of T-LGL-L was recognized among rather young patients and was associated with D661Y mutations in the STAT3 gene SH2 domain. In addition, all of them showed anemia including two cases with pure red cell aplasia. These results suggest the heterogeneity of T-LGL-L and a specific subtype with small variants of T-LGL-L. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  5. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  6. Nanomedicine approaches in acute lymphoblastic leukemia.

    Science.gov (United States)

    Tatar, Andra-Sorina; Nagy-Simon, Timea; Tomuleasa, Ciprian; Boca, Sanda; Astilean, Simion

    2016-09-28

    Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting. Nanomedicine approaches, especially by the use of nanoparticle-based compounds for the delivery of drugs, cancer diagnosis or therapeutics may represent new and modern ways in the near future anti-cancer therapies. This review offers an overview on the recent role of nanomedicine in the detection and treatment of acute lymphoblastic leukemia as resulting from a thorough literature survey. A short introduction on the basics of ALL is presented followed by the description of the conventional methods used in the ALL detection and treatment. We follow our discussion by introducing some of the general nano-strategies used for cancer detection and treatment. The detailed role of organic and inorganic nanoparticles in ALL applications is further presented, with a special focus on gold nanoparticle-based nanocarriers of antileukemic drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Bloodstream infections in pediatric patients with acute leukemia: Emphasis on gram-negative bacteria infections.

    Science.gov (United States)

    Kuo, Fu-Chun; Wang, Shih-Min; Shen, Ching-Fen; Ma, Yun-Ju; Ho, Tzong-Shiann; Chen, Jiann-Shiuh; Cheng, Chao-Neng; Liu, Ching-Chuan

    2017-08-01

    Acute leukemia is the most common pediatric hematological malignancy. Bloodstream infections (BSIs) are severe complications in these patients during chemotherapy. This study aims to explore clinical features, laboratory, and microbiological characteristics of BSIs in acute leukemic children. Patients aged leukemia or acute lymphocytic leukemia with BSIs from January 2004 to December 2013 were enrolled. BSIs was defined as positive isolate(s) of blood culture and associated with clinical findings. Clinical presentations, demographic features, and microbiological findings were retrospectively reviewed. In total, 126 isolates of 115 episodes of BSIs were identified from 69 patients (acute lymphocytic leukemia 56; acute myeloid leukemia 13). Gram-negative bacteria (GNB), gram-positive cocci, and fungi constituted 56.3%, 42.3%, and 2.4% of the pathogens, respectively. Eighty-three and a half percent of BSIs occurred along with neutropenia, and 73% had severe neutropenia. GNB was the leading pathogen of BSIs. The major GNBs were Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. White blood cell counts, absolute neutrophil counts, and platelet counts were significantly lower in patients of BSIs caused by GNB than gram-positive cocci. Plasma level of C-reactive protein was significant high in patients of GNB BSIs (179.8 mg/L vs. 127.2 mg/L; p = 0.005). Eighty-two percent of patients of E. coli, K. pneumonia, and P. aeruginosa BSIs had sepsis related organ failure or organ dysfunction. P. aeruginosa BSIs had the highest case-mortality (40%). Neutropenia was the major risk factor of BSIs in pediatric leukemic patients. BSIs of GNB were associated with severe neutropenia, systemic inflammatory responses, and high mortality. Copyright © 2015. Published by Elsevier B.V.

  8. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  9. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Strefford, J C; Sutton, L-A; Baliakas, P

    2013-01-01

    Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B...

  10. Clinical Practice Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL) in The Netherlands

    NARCIS (Netherlands)

    Kersting, Sabina; Neppelenbroek, Suzanne I. M.; Visser, Hein P. J.; van Gelder, Michel; Levin, Mark-David; Mous, Rogier; Posthuma, Ward; van der Straaten, Hanneke M.; Kater, Arnon P.

    2018-01-01

    In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact

  11. Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Lanemo Myhrinder, Anna; Hellqvist, Eva; Bergh, Ann-Charlotte

    2013-01-01

    Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface...

  12. p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Blume, C. J.; Hotz-Wagenblatt, A.; Hüllein, J.; Sellner, L.; Jethwa, A.; Stolz, T.; Slabicki, M.; Lee, K.; Sharathchandra, A.; Benner, A.; Dietrich, S.; Oakes, C. C.; Dreger, P.; te Raa, D.; Kater, A. P.; Jauch, A.; Merkel, O.; Oren, M.; Hielscher, T.; Zenz, T.

    2015-01-01

    Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We

  13. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation

    NARCIS (Netherlands)

    Mackus, W. J. M.; Kater, A. P.; Grummels, A.; Evers, L. M.; Hooijbrink, B.; Kramer, M. H. H.; Castro, J. E.; Kipps, T. J.; van Lier, R. A. W.; van Oers, M. H. J.; Eldering, E.

    2005-01-01

    We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgV(H) mutation status, and (3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL

  14. Not all IGHV3-21 chronic lymphocytic leukemias are equal

    DEFF Research Database (Denmark)

    Baliakas, Panagiotis; Agathangelidis, Andreas; Hadzidimitriou, Anastasia

    2015-01-01

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue...

  15. The influence of pregnancy on the development of autoimmunity in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Jønsson, Viggo; Bock, Johannes E; Hilden, Jørgen

    2006-01-01

    To examine whether pregnancy influences the development of autoimmunity in chronic lymphocytic leukemia (CLL), we studied 591 consecutive CLL patients (202 post-menopausal women and 389 men). The mean observation time for all patients was 3.8 years, corresponding to approximately 2200 person...

  16. Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Gunnarsson, Rebeqa; Mansouri, Larry; Isaksson, Anders

    2011-01-01

    High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic...

  17. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-06-27

    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 Del(5q); 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); Recurrent Adult Acute Myeloid Leukemia

  18. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-12-04

    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 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  19. [The role of genetic polymorphisms of interleukins in chronic lymphocytic leukemia in patients of different ages].

    Science.gov (United States)

    Sirotina, S S; Tikunova, T S; Proshchaev, K I; Efremova, O A; Batlutskaia, I V; Iakunchenko, T I; Sobianin, F I; Churnosov, M I; Alekseev, S M

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is a multifactorial disease, in which development the important role played the cytokine genes, in particular interleukins. This type of leukemia is more common in the elderly. The purpose of the study was to evaluate the association of genetic polymorphisms of interleukin with the development of chronic lymphocytic leukemia among residents of the Central Chernozem region of Russia. Genotyping of the -889C/T IL-1A, -590C/T IL-4 and VNTR IL-1 Ra was conducted in 206 patients with CLL and 307 individuals of the control group. The study found that the genetic risk factor for the development of CLL is allele -590T IL-4 (OR=-1,45). The development of thrombocytopenia in patients with CLL is associated with genetic variants -889T IL-1A (OR=1,95), -889TT IL-1A (OR=6,2) and IL-1Ra*1 (OR=-2,32).

  20. Cranial computerized tomography in children suffering from acute leukemia

    International Nuclear Information System (INIS)

    Metz, O.

    1981-01-01

    Cranial computerized (axial) tomography permits a more complete neurologic supervision of children with acute leukemia and a better knowledge of the frequency and varieties of cerebral complications in leukemia. Endocranial complications in acute leukemia are essentially infiltrative, hemorrhagic, infectious or iatrogenic. Cranial computerized tomography can demonstrate cerebral changes in meningeal leukemia, hemorrhages, calcifications, brain atrophy or leukencephalopathy. The preliminary results of cranial computerized tomography in childhood leukemia suggest that the iatrogenic main lesion of the brain due to combined radiation-chemotherapy is atrophy whereas that of the intrathecal cytostatic therapy is demyelination. Accurate diagnostics and control of possible cerebral complications in therapy of leukemia is essentially for appropriate therapeutic management. For that cranial computerized tomography is the best method to a effective supervision of the brain. (author)

  1. Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

    International Nuclear Information System (INIS)

    Ochoa-Hernández, Alejandra B; Bravo-Cuellar, Alejandro; Jave-Suarez, Luis F; Barros-Núñez, Patricio; Aguilar-Lemarroy, Adriana; Ramos-Solano, Moisés; Meza-Canales, Ivan D; García-Castro, Beatriz; Rosales-Reynoso, Mónica A; Rosales-Aviña, Judith A; Barrera-Chairez, Esperanza; Ortíz-Lazareno, Pablo C; Hernández-Flores, Georgina

    2012-01-01

    WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the WNT7A gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation. We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative WNT7A expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures. WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p ≤0.001). By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway. To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic

  2. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  3. [Infections in the child with acute leukemia].

    Science.gov (United States)

    Carrillo, J M; Jiménez, E; Jiménez, R

    1981-01-01

    One hundred and twenty-five febrile episodes in 82 children with acute leukemia were studied; 46% of the patients were from urban and 54% from rural areas. The origin of the fever was identified in 91% of the episodes, prevailing pneumonia, septicemia, chickenpox and herpes zoster. The etiological agent was identified in 46% of the cases. A viral predominance was evident, and among them varicela-zoster, following in importance gram-negative bacteria. Histoplasma capsulatum and Pneumocystis carinii were isolated in two occassions each. Sepsis was found more frequently in children with active leukemia than in those in remission (p less than 0.001). Forty-four febrile episodes occurred in patients with less than 1,000 neutrophils/ul. The daily-risk rate of infection was higher in children fom rural than in those from urban areas (p less than 0.001). After clinical and laboratory studies, methicillin and gentamicin were used, in addition to carbenicillin or trimethoprim-sulfamethoxazole is selected cases. This treatment was effective in 86% of the cases. Twelve (15%) children died, 6 of whom were in remission at that moment.

  4. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  5. Recurrent Cytogenetic Abnormalities in Acute Myeloid Leukemia.

    Science.gov (United States)

    Yang, John J; Park, Tae Sung; Wan, Thomas S K

    2017-01-01

    The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification. Brief morphologic, cytogenetic, and clinical characteristics are summarized, so as to provide a concise reference to cancer cytogenetic laboratories. Morphology based on FAB classification is used together with the current WHO classification due to frequent mentioning in a vast number of reference literatures. Characteristic chromosomal aberrations of other myeloid neoplasms such as myelodysplastic syndrome and myeloproliferative neoplasm will be discussed in separate chapters-except for certain abnormalities such as t(9;22) in de novo AML. Gene mutations detected in normal karyotype AML by cutting edge next generation sequencing technology are also briefly mentioned.

  6. MR imaging of the femoral marrow in adult acute leukemia. Correlation of MRI patterns with FAB subtype and prognosis

    International Nuclear Information System (INIS)

    Tanaka, Osamu; Takagi, Shojiro; Kobayashi, Yasuyuki; Ichikawa, Tamaki; Matsuura, Katsuhiko; Nagai, Jun

    1996-01-01

    MR imaging of the femoral marrow was performed in 36 patients with untreated acute myeloid leukemia (AML) and 7 patients with acute lymphocytic leukemia (ALL). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. The MRI patterns of the femoral marrow were compared among the FAB subtypes of acute leukemia, and the MRI patterns were correlated with prognosis. All five MRI patterns were observed in the femoral marrow in adult acute leukemia, and diffuse infiltration was most commonly seen (41.9%). A completely fatty marrow was also depicted in two cases (4.7%) and faint signal in four cases (9.3%) in spite of untreated acute leukemia. The M2 subtype of AML tended to be demonstrated as a minimally abnormal MRI finding, which was significantly different from the other types of AML. The patients who showed fatty marrow or faint signal were thought to have a good prognosis, while diffuse or heterogeneous infiltration was regarded as a poor prognostic sign. However, there were some exceptions to these rules, and no significant differences were revealed in prognosis between minimally abnormal and advanced MRI patterns. We concluded that MRI of the femoral marrow could be useful in the assessment of tumor volume of adult acute leukemia, and that there were limitations to predicting prognosis on the basis of the MRI manifestations. (author)

  7. Emerging therapies for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Caner Saygin

    2017-04-01

    Full Text Available Abstract Acute myeloid leukemia (AML is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH inhibitors, vadastuximab or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin, epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC inhibitors, bromodomain and extraterminal (BET inhibitors, FMS-like tyrosine kinase receptor 3 (FLT3 inhibitors, and antibody-drug conjugates (vadastuximab, as well as cell cycle inhibitors (volasertib, B-cell lymphoma 2 (BCL-2 inhibitors, and aminopeptidase inhibitors. These agents are actively undergoing clinical investigation alone or in combination with available chemotherapy.

  8. Current Management of Childhood Acute Myeloid Leukemia.

    Science.gov (United States)

    Rubnitz, Jeffrey E

    2017-02-01

    The outcome for children with acute myeloid leukemia (AML) has improved significantly over the past 30 years, with complete remission and overall survival rates exceeding 90 and 60%, respectively, in recent clinical trials. However, these improvements have not been achieved by the introduction of new agents. Instead, intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy have all contributed to this success. Nevertheless, novel therapies are needed, as the cure rates for many subtypes of childhood AML remain unacceptably low. Here, we briefly review advances in our understanding of the biology and genetics of AML, the results of recent clinical trials, and current recommendations for the treatment of children with AML.

  9. Computed tomographic findings of intracranial acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dong Woo; Ryu, Weon Don; Kim, Jong Sung; Koh, Byung Hee; Jeon, Seok Chol; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1990-07-15

    Computed tomographic (CT) abnormalities in the brain were retrospectively analyzed in 16 of 103 patients with acute leukemia confirmed by CSF cytology or combined surgery at Hanyang University Hospital, from August 1980 to August 1989. The results were as follows : 1. With FAB classification, the most frequent pathologic type was L1 : 8 cases (50%) 2. The range of age distribution showed typical pattern that ALL occurred below the 15 years old, and AML, over 15 years old. 3. Abnormal CT findings were ; Meningitis(2 cases), Mass(3), Thrombosis(1), Infarction(2), Edema(1), Hemorrhage(7), Hydrocephalus(2), Atrophy(2). 4. Most of infracranial hemorrhage were seen in M{sub 2} and M{sub 3} type.

  10. [Study on cytogenetic changes with relation to FAB classification in 397 patients with acute leukemias].

    Science.gov (United States)

    Huo, Fei-Fei; Liu, Xin; Sun, Zi-Min; Zhu, Wei-Bo; Zheng, Chang-Cheng; Wang, Jian; Wu, Zhi-Wei

    2011-02-01

    The purpose of study was to investigate the cytogenetic abnormality of acute leukemias (AL), to analyze the relationship in the chromosomal abnormality and the AL FAB types, and to explore the impact of the chromosomal abnormalities on the prognostic factors of AL. The chromosome karyotypes of 397 patients with AL were analyzed by means of bone marrow short-term culture and G banding technique. The results showed that in 319 out of 397 patients, the chromosome karyotypes could be analyzed, and the chromosomal abnormality occurred in 175 patients (54.9%). In the patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and acute mixed-lineage leukemia (AMLL), the chromosomal abnormality occurred respectively in 33 of 120 patients (27.5%), 129 of 252 patients (51.2%) and 13 of 25 patients (52.0%). Hyper-diploids, hypo-diploids and diploids occurred in 41 of 175 patients (23.4%), 22 of 175 patients (12.5%), and 112 of 175 patients (64.0%) respectively. In patients with AML the FAB type-associated chromosomal abnormality occurred in 69 of 129 patients (53.5%). It is concluded that chromosomal abnormalities exist in about 55% AL patients. Some special chromosomal abnormalities are cytogenetic characteristics of AL, and obviously correlated with AL FAB types, the combination of chromosomal detection with cytogenetics is useful for the diagnosis of AL, and the evaluation of therapeutic effects and prognosis.

  11. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). Copyright © 2016. Published by Elsevier Inc.

  12. Osteogenesis imperfecta and acute lymphoid leukemia: case report

    Directory of Open Access Journals (Sweden)

    Gabriel David Tarud

    2017-08-01

    Discussion: It is well described that genetic and chromosomal abnormalities increase the risk of leukemia, however the relationship between osteogenesis imperfecta and acute lymphoblastic leukemia is rare. In the world literature, there are few cases mentioning this association. It is important to continue observing the occurrence of later cases, which allow describing if there is a direct relationship between these two entities.

  13. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias.

    Science.gov (United States)

    Yan, Ying; Wieman, Eric A; Guan, Xiuqin; Jakubowski, Ann A; Steinherz, Peter G; O'Reilly, Richard J

    2009-12-29

    We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  14. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  15. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...

  16. Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2017-10-11

    Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  17. Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B.

    Science.gov (United States)

    Kashyap, Manoj K; Kumar, Deepak; Villa, Reymundo; La Clair, James J; Benner, Chris; Sasik, Roman; Jones, Harrison; Ghia, Emanuela M; Rassenti, Laura Z; Kipps, Thomas J; Burkart, Michael D; Castro, Januario E

    2015-07-01

    RNA splicing plays a fundamental role in human biology. Its relevance in cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B in primary leukemia cells derived from patients with chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD-895 and pladienolide-B induce an early pattern of mRNA intron retention - spliceosome modulation. This process was associated with apoptosis preferentially in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of these compounds was observed regardless of poor prognostic factors such as Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect of culture conditions that resemble the tumor microenvironment. In addition, the activity of these compounds was observed not only in vitro but also in vivo using the A20 lymphoma murine model. Overall, these findings give evidence for the first time that spliceosome modulation is a valid target in chronic lymphocytic leukemia and provide an additional rationale for the development of spliceosome modulators for cancer therapy. Copyright© Ferrata Storti Foundation.

  18. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  19. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    F.P.G. Silva (Fernando); I. Almeida (Inês); B. Morolli (Bruno); G. Brouwer-Mandema (Geeske); H. Wessels (Hans); R. Vossen (Rolf); H. Vrieling (Harry); E.W.A. Marijt (Erik); P.J.M. Valk (Peter); J.C. Kluin-Nelemans (Hanneke); W.R. Sperr (Wolfgang); W.D. Ludwig; M. Giphart-Gassler (Micheline)

    2009-01-01

    textabstractBackground: Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when

  20. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    Silva, Fernando P. G.; Almeida, Ines; Morolli, Bruno; Brouwer-Mandema, Geeske; Wessels, Hans; Vossen, Rolf; Vrieling, Harry; Marijt, Erik W. A.; Valk, Peter J. M.; Kluin-Nelemans, Hanneke C.; Sperr, Wolfgang R.; Ludwig, Wolf-Dieter; Giphart-Gassler, Micheline

    2009-01-01

    Background Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when other

  1. Chronic Subdural Hematoma Associated with Acute Biphenotypic Leukemia: Case Report

    OpenAIRE

    Besime Utku; Uygar Utku

    2015-01-01

    Spontaneous chronic subdural hematoma associated with neoplasm is a rare disorder. A rare case of chronic subdural hematoma associated with acute biphenotypic leukemia presented here. A 78-year-old woman who diagnosed as acute biphenotypic leukemia by hematology was complicated with a large chronic subdural hematoma. She presented to our emergency medicine service of hospital with left-sided weakness. Her non-contrast brain computerized tomography scan showed a non-traumatic right-sided, larg...

  2. Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Devesh Kumawat

    2018-01-01

    Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

  3. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according to cytog......Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  4. [Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

    Science.gov (United States)

    Matsuda, Isao; Nakamaki, Tsuyoshi; Amaya, Hiroshi; Kiyosaki, Masanobu; Kawakami, Keiichiro; Yamada, Kazunari; Yokoyama, Akihiro; Hino, Ken-ichiro; Tomoyasu, Shigeru

    2003-09-01

    A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

  5. Identification of an MLC suppressor cell population in acute leukemia

    International Nuclear Information System (INIS)

    Bryan, C.F.; Broxmeyer, H.E.; Hansen, J.; Pollack, M.; Dupont, B.

    1978-01-01

    The MLC data from the 20 nonsuppressing patients and the 10 suppressing leukemia patients were analyzed with regard to HLA-A, -B, and -C antigens in the leukemia patients and compared with the presence or absence of suppression. These results demonstrate a significant increase (p < 0.02, Mann-Whitney U test) of HLA antigens Al, A3, and A11 in the leukemia suppressor group. Seven of the 10 leukemia patients showing suppression were A1, A3, or A11, while only 4 of the 20 nonsuppressing leukemia patients carried any of these three HLA-A antigens. The studies demonstrate that a nonspecific suppression of MLC responses is observed in 33% of the patients with acute leukemia

  6. Infections in acute leukemia in Indian Children

    Directory of Open Access Journals (Sweden)

    B Roy

    2014-01-01

    Full Text Available Aims: In the present study acute leukemic children were studied to determine the incidence and principal site of infection, correlation with absolute neutrophil count, causative organisms and to standardize the initial empirical anti microbial therapy. Materials and methods: A total 40 children in the age group 6 month to 12 year with acute leukemia relapse were included in this study. A total 82 infectious episodes including 61 febrile episodes were investigated for infectious etiology. Results: We found that the frequency of infections increased significantly with the degree of immunocompromisation specially neutropenia (ANC < 500/cmm. The skin and soft tissue was the commonest site of infection (26.83%, followed by respiratory tract (21.95%. Staphylococcus nonhemolytic coagulase-negative (34%, followed by Klebsiella (17% were the most common organisms isolated from blood. Staphylococcus non-hemolytic coagulase-negative was also the commonest isolate (26% from other sites of infection. Most strains were sensitive to Cloxacillin, cephalosporin and aminoglycosides. Conclusion: For the treatment of febrile episodes, empirical use of beta-lactamase resistant penicillin e.g. Cloxacillin or cephalosporin combined with an aminoglycosides with a broad spectrum antifungal like fluconazole in selective cases at the first sign of infection is recommended. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 40-47 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9672

  7. A rare coexistence - Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Muhammet Bekir Hacioglu

    2015-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies.

  8. Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Gunn, Shelly R.; Mohammed, Mansoor S.; Gorre, Mercedes E.; Cotter, Philip D.; Kim, Jaeweon; Bahler, David W.; Preobrazhensky, Sergey N.; Higgins, Russell A.; Bolla, Aswani R.; Ismail, Sahar H.; de Jong, Daphne; Eldering, Eric; van Oers, Marinus H. J.; Mellink, Clemens H. M.; Keating, Michael J.; Schlette, Ellen J.; Abruzzo, Lynne V.; Robetorye, Ryan S.

    2008-01-01

    Array-based comparative genomic hybridization (array CGH) provides a powerful method for simultaneous genome-wide scanning and prognostic marker assessment in chronic lymphocytic leukemia (CLL). In the current study, commercially available bacterial artificial chromosome and oligonucleotide array

  9. The establishment of a cell line from an acute megakaryoblastic leukemia with evidence of emperipolesis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, C.Y.; Pabello, P.; Skinnider, L.F. [Univ. of Saskatchewan, Saskatoon (Canada)

    1994-09-01

    Acute megakaryoblstic leukemia is uncommon and comprises about 5% of acute non-lymphoid leukemia in the Franco-American-British (FAB) classification. Cell lines from such leukemias are relatively rare with only 6 reported in the literature. We have established a cell line from a case of acute megakaryoblastic leukemia arising in a 2-year-old child. Surface marker studies of the cells confirm their megakaryoblastic nature with 54.1% of the cells being CD61-positive. The cells have a doubling time of 72 hours. Morphologically they appear blast-like with Wright Giemsa stain and electron microscopy and some have small cytoplasmic blebs. Emperipolesis of one blast into another large one is occasionally seen and review of the original bone marrow specimen also showed emperipolesis of neutrophils into the megakaryoblasts (emperipolesis is a phenomenon in which a cell, usually a lymphocyte or neutrophil, enters another cell, moves about and leaves without undergoing phagocytosis). Karyotyping of the cells showed 45,XX + marker chromosome. The marker chromosome is apparently chromosome 16 with a small segment of a chromosome translocated to the terminal portion of chromosome 16. The origin of the translocated material will be elucidated using fluorescence in situ hybridization (FISH). This cell line may be useful in studying factors that contribute to the phenomenon of emperipolesis.

  10. Diagnostic problems among chronic lymphocytic leukemia and other indolent B-cell leukemias in a Japanese population.

    Science.gov (United States)

    Isobe, Yasushi; Tomomatsu, Junichi; Tsukune, Yutaka; Tsukada, Nobuhiro; Sasaki, Makoto; Sugimoto, Koichi; Komatsu, Norio

    2012-01-01

    Japanese chronic lymphocytic leukemia (CLL) provides a diagnostic dilemma due to the low incidence and the heterogeneity shown in its morphology and immunophenotype. We clarified the diagnostic problems in Japanese CLL through our retrospective observation. Between 2006 and 2011, we found a total of 48 cases with CLL and other indolent B-cell leukemias. We made a diagnosis of true CLL based on clinical, laboratory, immunophenotypic and cytogenetic data. Among the 48 cases, only 28 cases (58.3%) were diagnosed with true CLL. Morphologic evaluation using a forced-air dried preparation alone is not helpful to distinguish CLL from other indolent B-cell leukemias, including hairy cell leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma. CLL immunophenotypic score should be more strictly applied in Japan than in Western countries. Fluorescence in situ hybridization for CCND1/IGH, the presence of leukocytosis and lymphadenopathy at diagnosis, and the morphological evaluation using naturally air dried preparations are important clues to make a correct diagnosis of Japanese CLL.

  11. [Our experiences in the treatment of acute leukemias].

    Science.gov (United States)

    Jelić, S; Dragović, M; Vidaković, B; Plecas, V

    1976-01-01

    This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.

  12. ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CIRCULATING BLASTS PRESENTING AS SEVERE HYPERCALCEMIA

    Directory of Open Access Journals (Sweden)

    Z. Oloomi

    2007-05-01

    Full Text Available Hypercalcemia complicating malignancy is a rare complication in pediatric age group. In this article, we present a case with acute lymphoblastic leukemia presenting as severe hypercalcemia. A 10 years old girl presented with an acute onset of fever, nausea, vomiting, loss of weight, costovertebral pain and frequency. She was admitted with a presumptive diagnosis of acute pyelonephritis. Her examination showed mild hepatosplenomegaly. In laboratory studies she had sever hypercalcemia. Despite the absence of circulating blast, bone marrow aspiration was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide but the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in differential diagnosis even when there are no circulating blasts.

  13. Spontaneous Retroperitoneal Hemorrhage in a Patient with Prolymphocytic Transformation of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Gwynivere A. Davies

    2013-01-01

    Full Text Available Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but recognized entity. We present the case of a 76-year-old gentleman with a previous diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and a white blood cell count of 500 000 with prolymphocytes on peripheral blood examination. Chlorambucil and dexamethasone were initiated. He developed progressive anemia during his admission with no clear cause on initial CT examination. Bilateral hip pain began several days later and he was unfortunately diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This condition is rare and generally occurs in those receiving therapeutic anticoagulation or dialysis, with known bleeding disorders or vascular malformation, none of which were present in our patient. Pathology revealed marked leukemoid engorgement of the vessels of many organs with prolymphocytes. We discuss the potential etiologies and relationships between these critical diagnoses.

  14. Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

    Science.gov (United States)

    Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

    2018-03-11

    Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

  15. Allogeneic Hematopoietic Cell Transplantation in the Treatment of Chronic Lymphocytic Leukemia: Why and When?

    OpenAIRE

    Delioukina, Maria L.; Forman, Stephen J.

    2010-01-01

    Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in adults with an incidence rate of 4.2 per 100,000 per year. CLL frequently takes an indolent course, with some patients not requiring treatment for years, yet is incurable by currently available chemo- and immuno-therapeutic modalities. Despite high initial response rates, particularly to purine analogues, patients invariably relapse and subsequently develop resistance to therapy. The traditional “watchful waiting”...

  16. T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

    Science.gov (United States)

    Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

    2017-03-01

    Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

  17. Recurrent Malignant Melanoma Presenting as Isolated Pleural Metastases in a Patient with Chronic Lymphocytic Leukemia

    OpenAIRE

    Kartik Anand; Shashank Cingam; Prakash Peddi

    2017-01-01

    Isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma. We report an unusual case of a patient with chronic lymphocytic leukemia (CLL) and recurrent pleural effusions. The pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of CLL. However, chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. A video-assisted thoracoscopic surgery and biopsy of the affecte...

  18. Chronic Lymphocytic Leukemia (CLL) as an Unusual Cause of Rapid Airway Compromise

    Science.gov (United States)

    2017-04-15

    component of Wilford Hall Ambulatory Surgical Center (WHASC) internship and residency programs. 3. Please know that if you are a Graduate Health ...mail.mil Abstract: Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of non-Hodgkin’s lymphoma (NHL) in Western countries predominantly...and neck manifest as cervical lymphadenopathy or skin involvement, with the latter predicting poor prognosis [5, 8]. Upper airway obstruction

  19. Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

    Science.gov (United States)

    2017-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

  20. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  1. Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule.

    Science.gov (United States)

    Yu, Dehai; Du, Zhonghua; Li, Wei; Chen, Huaqiu; Ye, Songgen; Hoffman, Andrew R; Cui, Jiuwei; Hu, Ji-Fan

    2017-01-01

    Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP) for the treatment of ATL. We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL. © 2017 The Author(s). Published by S. Karger AG, Basel.

  2. Evaluation of Serum Leptin Level in Children With Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Iraj Shahramian

    2016-01-01

    Full Text Available Background Leptin is a multifunctional hormone plays an important role in regulating lipid, energy, homeostasis, angiogenesis, inflammation, hematopoiesis and cell cycle. This polypeptide is effective in growth and differentiation of leukemic cells through an Ob-R receptor expressed by them. Objectives The purpose of this study was to evaluate serum leptin levels in patients with acute leukemia and compare it in lymphoid and myeloid groups. Patients and Methods This analytical case-control study, conducted on 60 children in age ranged from 6 months to 16 years in two case and control groups in Ali ibn Abi Talib hospital, Zahedan. They matched based on age and gender and examined after their parent’s satisfaction according to the parental consent forms. None of patients had heart disease, digestive, glandular and metabolic problems, iron deficiency anemia and chronic kidney disease. After collecting the samples, leptin levels of both groups were measured with ELISA kit. Then, the gathered data were analyzed in SPSS-20 software, using independent t-test in considering of 95% confidence interval. Results Leptin serum levels in patients with acute leukemia and controls showed significant difference (P < 0.05. Leptin serum levels in patients with acute lymphoblastic leukemia and acute myeloblastic leukemia showed significant difference (P < 0.05. Leptin serum level in relation to age and gender groups was not statistically significant. Conclusions The findings of this study showed that in patients with acute leukemia, leptin serum levels increase independently of age and gender. In addition, leptin serum levels in acute lymphoid leukemia were higher than acute myeloid leukemia in this study.

  3. [Acute leukemias epidemiology in children. Part 1].

    Science.gov (United States)

    Mejía Aranguré, Juan Manuel; Ortega Alvarez, Manuel Carlos; Fajardo Gutiérrez, Arturo

    2005-01-01

    This paper is a revision from recent studies related to acute leukemia (AL) epidemiology in children. Cancer is the second cause of death in the pediatric population in Mexico between 1 to 15 years old. The AL are the types of cancer with more frequency in children below 15 years old and the cost of taking care of a child with cancer represents to the health institutions around 620 thousand dollars per year per case. In different places of the world the frequency of the AL has been increased and in Mexico City this is similar. Data from Instituto Mexicano del Seguro Social, in Mexico City, reports one of the highest worldwide. The environmental risk factors most consistent are the exposure in utero to X-ray, occupational exposure and pesticides. Other risk factors studied, as the exposure to electromagnetic fields, smoking and alcohol consumption in the parents, diet, and others, have had controversial results. These controversies can be explained by methodological mistakes in the studies and also because these studies did not assess the interaction between the susceptibility to AL and the environmental factors, a situation that could lead to the better understanding of the causal mechanisms of the disease. However it is recommended to have an attitude of prudent caution to accept that these factors are a cause of AL, and to have an energetic position in order to decrease the exposure to them and produce more adequate preventive strategies.

  4. The Epigenetic Landscape of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  5. Novel therapeutic options in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Especially for patients with intermediate or high-risk AML, which often show relapse. Allogeneic hematopoietic stem cell transplantation (HSCT remains the best chance for cure. Here we review the state of the art therapy of AML, with special focus on new developments in immunotherapies and cellular therapies including HSCT and particularly discuss the impact of new conditioning and haplo-identical donor regimens for HSCT, post-transplant strategies for preventing and treating relapse, and emerging novel therapeutic options.

  6. Unfavorable-risk acute myeloid leukemia dissected.

    Science.gov (United States)

    Strickland, Stephen A; Mohan, Sanjay R; Savona, Michael R

    2016-03-01

    Acute myeloid leukemia (AML) is an immensely heterogeneous disease based on the presence of varying combinations of morphologic, immunophenotypic, genetic, and molecular characteristics identified among those diagnosed with this disease. Although current therapeutic strategies provide a reasonable likelihood of achieving a complete remission for the majority of patients, relapse rates and subsequent disease-related mortality remain unacceptably high. Improved methods of risk stratification are needed to better identify patients at considerable risk of relapse in hopes of allowing for early therapeutic intervention and/or intensification that may lead to a higher likelihood of cure. The current status of risk stratification of AML and emerging technologies with potential to improve prognostic classification and outcomes are summarized in this review. Refinement of our understanding of the impact of current pretreatment AML cytogenetic, immunophenotypic, and molecular aberrations to predict outcomes and guide therapeutic decision-making is ongoing. Emerging data suggest that incorporation of the degree of posttreatment response and/or the detection of minimal residual disease can improve the accuracy of risk stratification for individual patients. Although pretreatment disease characteristics remain the hallmark of prognostication for AML patients, posttreatment parameters such as minimal residual disease assessment and degree of response to therapy possess the ability to further refine our identification of patients with unfavorable disease and thereby influence decisions regarding therapeutic planning.

  7. Acute Lymphoblastic Leukemia, Version 2.2015.

    Science.gov (United States)

    Alvarnas, Joseph C; Brown, Patrick A; Aoun, Patricia; Ballen, Karen Kuhn; Barta, Stefan K; Borate, Uma; Boyer, Michael W; Burke, Patrick W; Cassaday, Ryan; Castro, Januario E; Coccia, Peter F; Coutre, Steven E; Damon, Lloyd E; DeAngelo, Daniel J; Douer, Dan; Frankfurt, Olga; Greer, John P; Johnson, Robert A; Kantarjian, Hagop M; Klisovic, Rebecca B; Kupfer, Gary; Litzow, Mark; Liu, Arthur; Rao, Arati V; Shah, Bijal; Uy, Geoffrey L; Wang, Eunice S; Zelenetz, Andrew D; Gregory, Kristina; Smith, Courtney

    2015-10-01

    Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. Copyright © 2015 by the National Comprehensive Cancer Network.

  8. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  9. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  10. Alternative Donor Transplantation for Acute Myeloid Leukemia

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    Nelli Bejanyan

    2015-06-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT is a potentially curative therapy for adult patients with acute myeloid leukemia (AML, but its use for consolidation therapy after first remission with induction chemotherapy used to be limited to younger patients and those with suitable donors. The median age of AML diagnosis is in the late 60s. With the introduction of reduced-intensity conditioning (RIC, many older adults are now eligible to receive allo-HCT, including those who are medically less fit to receive myeloablative conditioning. Furthermore, AML patients commonly have no human leukocyte antigen (HLA-identical or medically suitable sibling donor available to proceed with allo-HCT. Technical advances in donor matching, suppression of alloreactivity, and supportive care have made it possible to use alternative donors, such as unrelated umbilical cord blood (UCB and partially HLA-matched related (haploidentical donors. Outcomes after alternative donor allo-HCT are now approaching the outcomes observed for conventional allo-HCT with matched related and unrelated donors. Thus, with both UCB and haploidentical donors available, lack of donor should rarely be a limiting factor in offering an allo-HCT to adults with AML.

  11. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia

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    Amit Pande

    2016-01-01

    Full Text Available Background: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. Materials and Methods: We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML, 13 were precursor B-acute lymphoblastic leukemia (B-ALL, 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid as per the WHO classification. Results: We found that the expression of CD71 was most prevalent in AMLs (84%, followed by T-ALL (50% and least in B-ALL (30%. Conclusion: This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

  12. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia.

    Science.gov (United States)

    Pande, Amit; Dorwal, Pranav; Jain, Dharmendra; Tyagi, Neetu; Mehra, Simmi; Sachdev, Ritesh; Raina, Vimarsh

    2016-01-01

    CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid) as per the WHO classification. We found that the expression of CD71 was most prevalent in AMLs (84%), followed by T-ALL (50%) and least in B-ALL (30%). This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

  13. Immunotherapy with natural killer cells: a possible approach for the treatment of Acute Myeloid Leukemia also in Brazil

    Directory of Open Access Journals (Sweden)

    Lúcia Silla

    Full Text Available SUMMARY The allogeneic hematopoietic stem cell transplantation (HSCT can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally.

  14. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2 , and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

  15. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

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    Shi Hao Tan

    2017-09-01

    Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs, which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

  16. Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells.

    Science.gov (United States)

    Petrov, Ivan; Suntsova, Maria; Mutorova, Olga; Sorokin, Maxim; Garazha, Andrew; Ilnitskaya, Elena; Spirin, Pavel; Larin, Sergey; Kovalchuk, Olga; Prassolov, Vladimir; Zhavoronkov, Alex; Roumiantsev, Alexander; Buzdin, Anton

    2016-11-19

    Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

  17. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

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    Marc Heincelman MD

    2016-09-01

    Full Text Available Acute lymphoblastic leukemia (ALL in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

  18. Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia.

    Science.gov (United States)

    Somasundaram, Rajesh; Prasad, Mahadesh A J; Ungerbäck, Jonas; Sigvardsson, Mikael

    2015-07-09

    B-lymphocyte development in the bone marrow is controlled by the coordinated action of transcription factors creating regulatory networks ensuring activation of the B-lymphoid program and silencing of alternative cell fates. This process is tightly connected to malignant transformation because B-lineage acute lymphoblastic leukemia cells display a pronounced block in differentiation resulting in the expansion of immature progenitor cells. Over the last few years, high-resolution analysis of genetic changes in leukemia has revealed that several key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and PAX5, are genetically altered in a large portion of the human B-lineage acute leukemias. This opens the possibility of directly linking the disrupted development as well as aberrant gene expression patterns in leukemic cells to molecular functions of defined transcription factors in normal cell differentiation. This review article focuses on the roles of transcription factors in early B-cell development and their involvement in the formation of human leukemia. © 2015 by The American Society of Hematology.

  19. THERAPY-RELATED MYELOID NEOPLASMS IN CHRONIC LYMPHOCYTIC LEUKEMIA AND WALDENSTROM MICROGLOBULINEMIA

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    Alessandra Tedeschi

    2011-01-01

    Full Text Available

    Secondary myelodisplasia (MDS and acute myeloide leukaemia (AML are frequent long term complications in Chronic Lymphocytic Leukemia (CLL and Waldesntrom Macroglobulinemia (WM patients. Although disease-related immune-suppression plays a crucial role in leukemogenesis there is great concern that therapy may further increase the risk of developing these devastating complications.

    Nucleoside analogs (NA and alkilator agents are considered appropriate agents in the treatment of both CLL and WM patients. Prolonged immunosuppression related to nucleoside analogs therapy and the incorporation of these agents or their metabolites into DNA, with potentially mutagenic action, leads to speculation that their therapeutic use might be responsible for an increased incidence of second cancer especially when combined with other DNA damaging agents like alkylators. In this review the published studies considering the occurrence of secondary MDS and AML in CLL and WM patients are reported and the potential role of chemotherapeutic agents in leukemogenesis is discussed.

  20. A case report of acute myeloid leukemia and neurofibromatosis 1

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    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a 65-year old patient affected by neurofibromatosis 1, documented by the presence of germ-line mutation on the NF1 gene, who developed various hyperproliferative malignant and benign diseases. He was brought to our attention for the diagnosis of acute myeloid leukemia revealed by major fatigue and dyspnea. The disease characteristics at diagnosis were hyperleukocytosis and complex karyotype with the inversion of the chromosome 16, classifying as a high-risk leukemia. The association between leukemia and neurofibromatosis 1 is controversial and needs to be further investigated. Nevertheless, such patients present a wide number of comorbidities that make therapeutic strategies most difficult.

  1. Temozolomide and cisplatin in relapsed/refractory acute leukemia

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    Rasul Muhammad

    2009-05-01

    Full Text Available Abstract Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5. Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25% patients demonstrated a significant reduction in bone marrow blasts.

  2. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    Does-van den Berg, A. van der.

    1980-01-01

    Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

  3. Clinical value of blood lipid, serum β2-microglolulin and tumor necrosis factor-α level in patients with acute leukemia

    International Nuclear Information System (INIS)

    Shen Xiaohua; Huang Zhairong; Yang Yongqing

    2010-01-01

    Objective: To study on diagnosis value of blood lipid, serum β 2 -microglolulin (β 2 -MG) and tumor necrosis factor-α (TNF-α) in acute leukemia. Methods: The serum β 2 -MG and TNF-α (with radioimmunoassay) blood lipid (with biochemistry) levels were determined in 123 patients with acute leukemia as well as 36 controls, then conducted the correlative tests. Results: Serum β 2 -MG, TNF-α and triglyceride levels in 123 patients including 46 patients with acute monocytic leukemia, 32 patients with acute lymphocytic leukemia and 45 patients with acute nonlymphocytic leukemia were significantly higher than those in 36 controls (t=4.123-6.815, P 0.05); The serum cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, apolipoprotein A levels in 123 patients with acute leukemia were significantly lower than those in 36 controls (t=2.110-2.574, P 0.05). Conclusion: The determination of blood lipid, serum β 2 -MG and TNF-α level might be useful for diagnosing acute leukemia and reflecting the prognostic value. (authors)

  4. Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Baou, Maria; Kohlhaas, Susan L; Butterworth, Michael; Vogler, Meike; Dinsdale, David; Walewska, Renata; Majid, Aneela; Eldering, Eric; Dyer, Martin J S; Cohen, Gerald M

    2010-09-01

    Bortezomib has been successfully used in the treatment of multiple myeloma and has been proposed as a potential treatment for chronic lymphocytic leukemia. In this study we investigated the mechanism by which bortezomib induces apoptosis in chronic lymphocytic leukemia cells. Using western blot analysis, we monitored the regulation of BCL2 family members, proteins of the unfolded protein response (endoplasmic reticulum stress response) and activation of caspases in relation to induction of apoptosis (measured by annexin-propidium iodide staining and loss of mitochondrial membrane potential) by bortezomib in chronic lymphocytic leukemia cells. Bortezomib induced apoptosis through activation of the mitochondrial pathway independently of changes associated with endoplasmic reticulum stress. Perturbation of mitochondria was regulated by a rapid and transcription-independent increase of NOXA protein, which preceded release of cytochrome c, HtrA2, Smac and activation of caspase-9 and -3. NOXA had a short half life (approximately 1-2 h) and was ubiquitinated on at least three primary lysine residues, resulting in proteasomal-dependent degradation. Down-regulation of NOXA, using short interfering RNA in chronic lymphocytic leukemia cells, decreased bortezomib-induced apoptosis. Finally bortezomib when combined with seliciclib resulted in a stronger and earlier increase in NOXA protein, caspase-3 cleavage and induction of apoptosis in chronic lymphocytic leukemia cells. These results highlight a critical role for NOXA in bortezomib-induced apoptosis in chronic lymphocytic leukemia cells and suggest that this drug may become more efficient for the treatment of chronic lymphocytic leukemia if combined with other agents able to interfere with the basal levels of MCL1.

  5. Clinical efficacy and safety of imatinib in the management of Ph+ chronic myeloid or acute lymphoblastic leukemia in Chinese patients

    Science.gov (United States)

    Zhu, Yu; Qian, Si-Xuan

    2014-01-01

    Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukemia (CML) and functions by targeting BCR-ABL tyrosine kinases. Imatinib has substantially changed the clinical management and improved the prognosis of CML and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). Here, we review the pharmacology, mode of action, and pharmacokinetics of imatinib; Chinese efficacy studies in CML and Ph+ ALL; safety and tolerability; patient-focused perspectives, such as quality of life, patient satisfaction, acceptability, and adherence; and uptake of imatinib. PMID:24623982

  6. Leukemia

    International Nuclear Information System (INIS)

    Kamada, Nanao

    1992-01-01

    This chapter deals with clinical features associated with chromosomal aberration in A-bomb survivors with leukemia. Clinical features are presented by dividing them into three categories: (1) those from preleukemic stage up to the development of overt leukemia, (2) those specific to A-bomb survivors, and (3) changes in chromosomes. Many of the A-bomb survivors had normocytic anemia and leukopenia for a long time preceding the development of overt leukemia. A woman exposed to 483 rad (estimated by the T65D) 800 m from the hypocenter who finally developed erythroleukemia is presented; and in 6 other A-bomb survivors, abnormal hematological findings up to the development of overt acute leukemia are mentioned. Hematological findings in chronic myeloid leukemia (CML) are discussed by presenting two cases: one was exposed at 800 m from the hypocenter and developed CML 35 years later and the other was exposed at 1800 m and developed it 22 years later. In A-bomb survivors, acute leukemia tended to be associated with smaller number of leukemic cells in both peripheral blood and bone marrow, and non-leukemic leukemia was observed. Chromosomal analysis has been made in 75 A-bomb survivors with acute leukemia and 55 CML A-bomb survivors. In acute leukemic patients exposed to one Gy or more, bone marrow stem cells with chromosomal aberrations occurring at the time of exposure were considered to be proliferated by various factors. A-bomb survivors with CML are found to be characterized by having Philadelphia chromosome, t(9;22)(q34;q11). (N.K.)

  7. CT findings of brain atrophy after chemotherapy in acute leukemia

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    Lim, Jun; Park, Seog Hee; Kim, Choon Yul; Bahk, Yong Whee [Catholic University Medicine College, Seoul (Korea, Republic of)

    1988-10-15

    A study was performed to evaluate the atrophic changes of the central nerve system after chemotherapy in the patients with acute leukemia. The computed tomographic findings and medical records of 20 proven acute leukemia patients under 35 years-old who developed various CNS symptoms and signs during and/or after 2 courses of chemotherapy were reviewed. The results were as follows: 1. Age distribution was from 14 to 5 years (mean was 26 years). Male was 15. 2. Presenting clinical symptoms and signs were headache (16/20), nausea and vomiting (11/20) and loss of consciousness (5/20). 3. Brain atrophy was noted in 16 patients including cortical and subcortical atrophy 15 cases and subcortical atrophy 1 case. 4. Two cases of hemorrhage, one each of intracranial hematoma and chronic subdural hematoma were found in addition to brain atrophy. This showed that chemotherapeutic agents cause brain atrophy in a considerable number of the patients with symptomatic acute leukemia.

  8. Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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    Khadijeh Khosravi

    2016-05-01

    Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

  9. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    Science.gov (United States)

    2017-07-18

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  10. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  11. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  12. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  13. General Information about Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  14. General Information about Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  15. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  16. Treatment Options for Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  17. Stages of Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  18. Acute Myeloid Leukemia (AML) (For Parents)

    Science.gov (United States)

    ... fluid (CSF, the fluid surrounding the brain and spinal cord) for examination in a lab. Flow cytometry tests. Using markers on leukemia cells collected from the blood, bone marrow, and/or CSF, doctors can determine the type ...

  19. Leukemias involving abdominal and pelvic lymph nodes: evaluation with contrast-enhanced MDCT.

    Science.gov (United States)

    Zhang, Ge; Yang, Zhi-Gang; Bai, Jiao; Li, Yuan; Xu, Hua-Yan; Long, Qi-Hua

    2014-10-01

    To clarify features of lymph nodes associated with leukemia purposing to offer help for imaging diagnosis and differential diagnosis of leukemia. We retrospectively analyzed 47 patients with clinically proven leukemia involving the abdominal and pelvic lymph nodes. Of these 47 patients, 10 had acute myeloid leukemia, 9 had acute lymphocytic leukemia, and 28 had chronic lymphocytic leukemia. MDCT was used to determine lymph node features such as morphology, growth patterns, size, enhancement patterns, anatomical distribution, and manifestations in extramedullary organs. Incidence of leukemia was higher in men than in women. Enlarged lymph nodes were more frequently conglomerated in chronic lymphocytic leukemia (96.4%) than in acute myeloid leukemia (50%) and acute lymphocytic leukemia (55.6%; P leukemia were larger than those associated with acute myeloid and lymphocytic leukemias (P leukemias with respect to enhancement patterns (all P > 0.05). The lymph nodes commonly associated with these three leukemias were located in the lesser omentum, upper and lower para-aortic regions, and groin region. Our study showed that contrast-enhanced MDCT could accurately determine the enhancement patterns and anatomical distribution of lymph nodes associated with leukemia. Therefore, it is helpful for imaging diagnosis and differential diagnosis of leukemia.

  20. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  1. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  2. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  3. Multiplex acute leukemia cytosensing using multifunctional hybrid electrochemical nanoprobes at a hierarchically nanoarchitectured electrode interface

    Science.gov (United States)

    Zheng, Tingting; Tan, Tingting; Zhang, Qingfeng; Fu, Jia-Ju; Wu, Jia-Jun; Zhang, Kui; Zhu, Jun-Jie; Wang, Hui

    2013-10-01

    We have developed a robust, nanobiotechnology-based electrochemical cytosensing approach with high sensitivity, selectivity, and reproducibility toward the simultaneous multiplex detection and classification of both acute myeloid leukemia and acute lymphocytic leukemia cells. The construction of the electrochemical cytosensor involves the hierarchical assembly of dual aptamer-functionalized, multilayered graphene-Au nanoparticle electrode interface and the utilization of hybrid electrochemical nanoprobes co-functionalized with redox tags, horseradish peroxidase, and cell-targeting nucleic acid aptamers. The hybrid nanoprobes are multifunctional, capable of specifically targeting the cells of interest, amplifying the electrochemical signals, and generating distinguishable signals for multiplex cytosensing. The as-assembled electrode interface not only greatly facilitates the interfacial electron transfer process due to its high conductivity and surface area but also exhibits excellent biocompatibility and specificity for cell recognition and adhesion. A superstructured sandwich-type sensor geometry is adopted for electrochemical cytosensing, with the cells of interest sandwiched between the nanoprobes and the electrode interface. Such an electrochemical sensing strategy allows for ultrasensitive, multiplex acute leukemia cytosensing with a detection limit as low as ~350 cells per mL and a wide linear response range from 5 × 102 to 1 × 107 cells per mL for HL-60 and CEM cells, with minimal cross-reactivity and interference from non-targeting cells. This electrochemical cytosensing approach holds great promise as a new point-of-care diagnostic tool for early detection and classification of human acute leukemia and may be readily expanded to multiplex cytosensing of other cancer cells.We have developed a robust, nanobiotechnology-based electrochemical cytosensing approach with high sensitivity, selectivity, and reproducibility toward the simultaneous multiplex

  4. In vitro radiosensitivity of human leukemia cell lines

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Greenberger, J.S.; Schmidt, A.; Karpas, A.; Moloney, W.C.; Little, J.B.

    1981-01-01

    The in vitro radiobiologic survival values (anti n, D 0 ) of four tumor lines derived from human hematopoietic tumors were studied. These cell lines were HL60 promyelocytic leukemia; K562 erythroleukemia; 45 acute lymphocytic leukemia; and 176 acute monomyelogenous leukemia. More cell lines must be examined before the exact relationship between in vitro radiosensitivity and clinical radiocurability is firmly established

  5. The MLL recombinome of acute leukemias in 2013.

    Science.gov (United States)

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    2013-11-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

  6. [Research Progress of Novel Small Molecule Drugs in the Treatment of Chronic Lymphocytic Leukemia -Review].

    Science.gov (United States)

    Qiao, Jing-Qiao; He, Miao; Zhang, Shu-Ting; Bai, Hai

    2017-02-01

    Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western population, is characterized by accumulation of mature-looking CD5 + /19 + /23 + B cells in peripheral blood, bone marrow, and lymphatic organs. Over the last 20 years, there has been a dramatic change in therapy for CLL, the complete response rate increased from the initial explosion of new active agents that provide a very effective solution for patients with recurrent/refractory disease as well as those who harbor poor cytogenetic abnormalities. This review focuses on some of the novel small molecule drugs that have either been approved or are at the forefront of clinical development in the treatment of patients with CLL, including tyrosine kinase inhibitior ibrutinib, PI3K inhibitor idelalisib, Syk inhibitor, BCL-2 inhibitor and so on.

  7. Automated Analysis of Clinical Flow Cytometry Data: A Chronic Lymphocytic Leukemia Illustration.

    Science.gov (United States)

    Scheuermann, Richard H; Bui, Jack; Wang, Huan-You; Qian, Yu

    2017-12-01

    Flow cytometry is used in cell-based diagnostic evaluation for blood-borne malignancies including leukemia and lymphoma. The current practice for cytometry data analysis relies on manual gating to identify cell subsets in complex mixtures, which is subjective, labor-intensive, and poorly reproducible. This article reviews recent efforts to develop, validate, and disseminate automated computational methods and pipelines for cytometry data analysis that could help overcome the limitations of manual analysis and provide for efficient and data-driven diagnostic applications. It demonstrates the performance of an optimized computational pipeline in a pilot study of chronic lymphocytic leukemia data from the authors' clinical diagnostic laboratory. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

    Directory of Open Access Journals (Sweden)

    Bekker-Méndez Vilma

    2011-08-01

    Full Text Available Abstract Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR, and the standardized average annual incidence rates (SAAIR per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level. Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3; acute lymphoblastic leukemia (ALL was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million, followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million, and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million. The 1-4 years age group had the highest SAAIR for ALL (77.7 per million. For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million. The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8% were

  9. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.

    Science.gov (United States)

    Pérez-Saldivar, María Luisa; Fajardo-Gutiérrez, Arturo; Bernáldez-Ríos, Roberto; Martínez-Avalos, Armando; Medina-Sanson, Aurora; Espinosa-Hernández, Laura; Flores-Chapa, José de Diego; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; Alvarez-Rodríguez, Francisco Javier; Bolea-Murga, Victoria; Flores-Lujano, Janet; Rodríguez-Zepeda, María Del Carmen; Rivera-Luna, Roberto; Dorantes-Acosta, Elisa María; Jiménez-Hernández, Elva; Alvarado-Ibarra, Martha; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Duarte-Rodríguez, David Aldebarán; Paredes-Aguilera, Rogelio; Del Campo-Martínez, María de Los Ángeles; Cárdenas-Cardos, Rocío; Alamilla-Galicia, Paola Hillary; Bekker-Méndez, Vilma Carolina; Ortega-Alvarez, Manuel Carlos; Mejia-Arangure, Juan Manuel

    2011-08-17

    Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive

  10. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  11. Erythema multiforme in a patient with recurrent non-hodgkins lymphoma/chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Siva Kumara Shankari

    2012-01-01

    Full Text Available Erythema multiforme major (EMM is a hypersensitivity reaction usually secondary to medications, viruses or other infections. Its presentation is fairly typical with a symmetrical distribution of vesicles, bullae or targeted lesions on the upper body, arms, legs, palms, feet and oral mucosa. The authors present a delineated case of EMM in association with chronic lymphocytic leukemia (CLL and non-Hodgkin′s lymphoma (NHL with a very unusual clinical presentation evolving overtime into a unique, almost dermatomal distribution. Typical therapies were not initially helpful and intravenous immunoglobulin antibody had to be administered.

  12. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia.

    Science.gov (United States)

    Parikh, Sameer A; Keating, Michael J; O'Brien, Susan; Wang, Xuemei; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Estrov, Zeev; Badoux, Xavier; Lerner, Susan; Wierda, William G

    2011-08-25

    Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation.

  13. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

  14. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    OpenAIRE

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the...

  15. Detection of Hodgkin Transformation in a Case of Chronic Lymphocytic Leukemia by PET/CT

    Directory of Open Access Journals (Sweden)

    Sabire Yılmaz

    2014-06-01

    Full Text Available Richter’s transformation (RT represents the development of high grade lymphoma, most commonly diffuse large B-cell lymphoma, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL. CLL/SLL may convert also to Hodgkin’s lymphoma, the so-called Hodgkin’s variant of Richter transformation. Histopathological proof is needed to confirm a definitive diagnosis. Patients with RT generally have a poor prognosis, with prompt recognition optimise clinical management. Whole-body PET scan with 18F-FDG can be used for detection of RT of CLL/SLL. We describe the case of 64-year-old woman with CLL/SLL who developed Hodgkin lymphoma detected with PET/CT.

  16. Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Pozdnyakova, Olga; Campigotto, Federico; DeAngelo, Daniel J; Stone, Richard M; Neuberg, Donna; Hasserjian, Robert P

    2015-07-01

    The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.

  17. Serum hepcidin level and disease course of acute leukemia in ...

    African Journals Online (AJOL)

    Acute leukemia (AL) is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is ...

  18. Cutis verticis gyrata secondary to acute monoblastic leukemia.

    Science.gov (United States)

    Passarini, B; Neri, I; Patrizi, A; Masina, M

    1993-04-01

    A 64-year-old man affected by acute monoblastic leukemia developed a cutis verticis gyrata during the terminal phase of hemopathy. The association between these two diseases is rare. The classification of cutis verticis gyrata in primary essential, primary non-essential and secondary forms is reviewed. Performing a skin biopsy is necessary in the diagnostic approach to patients with cutis verticis gyrata.

  19. Molecular mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    W.J.E. Tissing (Wim)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) is the most common form of cancer in children, with 110 – 120 newly diagnosed children in the Netherlands each year. ALL is a haematological malignancy of lymphoid precursor cells and can be divided into two sub-groups: B-cell precursor ALL and

  20. Pseudo Chediak-Higashi anomaly in acute myelomonocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rao Seema

    2009-04-01

    Full Text Available Pseudo Chediak-Higashi anomaly in acute leukemia is a rarely described entity. The significance of this intriguing morphological finding largely remains unknown, although some authors have predicted a poorer outcome in such cases because of a higher susceptibility to fulminant infections. Our case also had a fatal outcome.

  1. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...

  2. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  3. The MLL recombinome of acute leukemias in 2017

    Science.gov (United States)

    Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. PMID:28701730

  4. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  5. VINCRISTINE DISPOSITION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    DEGRAAF, SSN; BLOEMHOF, H; VENDRIG, DEMM; UGES, DRA

    Vincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well-defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new

  6. Pneumatosis Intestinalis in a Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Abhishek Mangaonkar

    2015-01-01

    Full Text Available Pneumatosis Intestinalis is a rare condition characterized by the presence of gas within the intestinal wall. We describe a case of a 33-year-old woman with acute promyelocytic leukemia who developed nausea and nonbloody diarrhea. CT showed intramural air in transverse and descending colon. Patient clinically improved with conservative management.

  7. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  8. Translational Studies in Elderly Patients with Acute Myeloid Leukemia

    NARCIS (Netherlands)

    B. van der Holt (Bronno)

    2007-01-01

    textabstractThe production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid leukemia (AML) is a clonal disease, which is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a severe

  9. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...

  10. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Talibov, Madar; Lehtinen-Jacks, Susanna; Martinsen, Jan Ivar

    2014-01-01

    OBJECTIVE: The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). METHODS: Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden and Iceland from 1961-2005 and 76...

  11. The role of B-cell receptor inhibitors in the treatment of patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Wiestner, Adrian

    2015-12-01

    Chronic lymphocytic leukemia is a malignancy of mature auto-reactive B cells. Genetic and functional studies implicate B-cell receptor signaling as a pivotal pathway in its pathogenesis. Full B-cell receptor activation requires tumor-microenvironment interactions in lymphoid tissues. Spleen tyrosine kinase, Bruton's tyrosine kinase, and the phosphatidylinositol 3-kinase (PI3K) δ isoform are essential for B-cell receptor signal transduction but also mediate the effect of other pathways engaged in chronic lymphocytic leukemia cells in the tissue-microenvironment. Orally bioavailable inhibitors of spleen tyrosine kinase, Bruton's tyrosine kinase, or PI3Kδ, induce high rates of durable responses. Ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, and idelalisib, a selective inhibitor of PI3Kδ, have obtained regulatory approval in chronic lymphocytic leukemia. Ibrutinib and idelalisib are active in patients with high-risk features, achieving superior disease control in difficult-to-treat patients than prior best therapy, making them the preferred agents for chronic lymphocytic leukemia with TP53 aberrations and for patients resistant to chemoimmunotherapy. In randomized trials, both ibrutinib, versus ofatumumab, and idelalisib in combination with rituximab, versus placebo with rituximab improved survival in relapsed/refractory chronic lymphocytic leukemia. Responses to B-cell receptor inhibitors are mostly partial, and within clinical trials treatment is continued until progression or occurrence of intolerable side effects. Ibrutinib and idelalisib are, overall, well tolerated; notable adverse events include increased bruising and incidence of atrial fibrillation on ibrutinib and colitis, pneumonitis and transaminase elevations on idelalisib. Randomized trials investigate the role of B-cell receptor inhibitors in first-line therapy and the benefit of combinations. This review discusses the biological basis for targeted therapy of chronic lymphocytic

  12. Migration of acute lymphoblastic leukemia cells into human bone marrow stroma.

    Science.gov (United States)

    Makrynikola, V; Bianchi, A; Bradstock, K; Gottlieb, D; Hewson, J

    1994-10-01

    Most cases of acute lymphoblastic leukemia (ALL) arise from malignant transformation of B-cell precursors in the bone marrow. Recent studies have shown that normal and leukemic B-cell precursors bind to bone marrow stromal cells through the beta-1 integrins VLA-4 and VLA-5, thereby exposing early lymphoid cells to regulatory cytokines. It has been recently reported that the pre-B cell line NALM-6 is capable of migrating under layers of murine stromal cells in vitro (Miyake et al. J Cell Biol 1992;119:653-662). We have further analyzed leukemic cell motility using human bone marrow fibroblasts (BMF) as a stromal layer. The precursor-B ALL cell line NALM-6 rapidly adhered to BMF, and underwent migration or tunneling into BMF layers within 5 h, as demonstrated by light and electron microscopy, and confirmed by a chromium-labeling assay. Migration was also observed with the precursor-B ALL lines Reh and KM-3, with a T leukemia line RPMI-8402, the monocytic line U937, and the mature B line Daudi. In contrast, mature B (Raji), myeloid (K562, HL-60), and T lines (CCRF-CEM, MOLT-4) did not migrate. When cases of leukemia were analyzed, BMF migration was largely confined to precursor-B ALL, occurring in eight of 13 cases tested. Of other types of leukemia, migration was observed in one of four cases of T-ALL, but no evidence was seen in six acute myeloid leukemias and two patients with chronic lymphocytic leukemia. Only minimal migration into BMF was observed with purified sorted CD10+ CD19+ early B cells from normal adult marrow, while normal mature B lymphocytes from peripheral blood did not migrate. ALL migration was inhibited by monoclonal antibodies to the beta sub-unit of the VLA integrin family, and by a combination of antibodies to VLA-4 and VLA-5. Partial inhibition was also observed when leukemic cells were incubated with antibodies to VLA-4, VLA-5, or VLA-6 alone. In contrast, treatment of stromal cells with antibodies to vascular cell adhesion molecule or

  13. Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

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    Yahui Ding

    2016-09-01

    Full Text Available Abstract Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML are largely attributed to leukemia stem cells (LSCs which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. Methods The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. Results The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C, alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. Conclusions Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.

  14. Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress report No. 17, July 1976--October 1977

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, D.K.

    1977-07-22

    The primary objective of the proposed research will be elucidation of the etiology and pathogenesis of bovine leukemia. We have consistently demonstrated C-type particles in mitogen stimulated lymphocyte cultures from leukemic cows and cows with a persistent lymphocytosis. These particles have been concentrated and partially purified by continuous flow, density gradient, ultracentrifugation. Newborn calves and late stage bovine fetuses have been inoculated with these concentrated cell free preparations. Our current study involves extensive monitoring of these inoculated animals to detect early pre-cancerous changes. The following parameters are being measured: the serological titer against a bovine leukemia associated antigen; the percentage of lymphocytes showing nuclear pockets; the percentage of mitogen stimulated lymphocytes with C-type particles adherent to their surface; the percentage of B-lymphocytes in the peripheral circulation; the complete blood count; and the quantity of bovine leukemia virus (BLV) production as determined by the syncytia induction assay. Additional proposals include: using the monitoring parameters to study animals with the juvenile and thymic forms of leukemia; the examination of adult lymphosarcoma cases to determine which tissues harbor BLV; and lymphocyte subpopulation work to further define which cell types are associated with BLV production and tumor formation.

  15. Survival of patients with mixed phenotype acute leukemias: A large population-based study.

    Science.gov (United States)

    Shi, Runhua; Munker, Reinhold

    2015-06-01

    Little is known about the incidence and treatment outcome of patients with acute biphenotypic leukemias. The World Health Organization (WHO) established the term of acute leukemia of ambiguous phenotype in 2001 (revised in 2008) introducing the term of mixed phenotype acute leukemias. Using the database of the Surveillance, Epidemiology, and End Results registry (SEER), we identified 313 patients with mixed phenotype acute leukemias and compared them with 14,739 patients with acute lymphoblastic leukemia and 34,326 patients with acute myelogenous leukemias diagnosed between 2001 and 2011. As a further control group, 1777 patients were included who were not classified as myeloid, lymphoid or biphenotypic (other acute leukemias). The incidence of mixed phenotype acute leukemias is 0.35 cases/1,000,000 person-years. In a multivariate analysis, the prognosis depends strongly on age (as with other leukemias) and it has the worst outcome of all four types of leukemia. However, the prognosis has improved, comparing 2001-2005 with 2006-2011. We present the first comprehensive, population-based study of acute biphenotypic or mixed phenotype acute leukemias according to the WHO classification. Especially in older patients, the prognosis is unfavorable and new treatments should be investigated. Published by Elsevier Ltd.

  16. Mechanistic Study of the Phytocompound, 2-β-D-Glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne in Human T-Cell Acute Lymphocytic Leukemia Cells by Using Combined Differential Proteomics and Bioinformatics Approaches

    Directory of Open Access Journals (Sweden)

    Jeng-Yuan Shiau

    2015-01-01

    Full Text Available Bidens pilosa, a medicinal herb worldwide, is rich in bioactive polyynes. In this study, by using high resolution 2-dimensional gel electrophoresis coupled with mass spectrometry analysis, as many as 2000 protein spots could be detected and those whose expression was specifically up- or downregulated in Jurkat T cells responsive to the treatment with 2-β-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHTT can be identified. GHTT treatment can upregulate thirteen proteins involved in signal transduction, detoxification, metabolism, energy pathways, and channel transport in Jurkat cells. Nine proteins, that is, thioredoxin-like proteins, BH3 interacting domain death agonist (BID protein involving apoptosis, methylcrotonoyl-CoA carboxylase beta chain, and NADH-ubiquinone oxidoreductase, were downregulated in GHTT-treated Jurkat cells. Further, bioinformatics tool, Ingenuity software, was used to predict signaling pathways based on the data obtained from the differential proteomics approach. Two matched pathways, relevant to mitochondrial dysfunction and apoptosis, in Jurkat cells were inferred from the proteomics data. Biochemical analysis further verified both pathways involving GHTT in Jurkat cells. These findings do not merely prove the feasibility of combining proteomics and bioinformatics methods to identify cellular proteins as key players in response to the phytocompound in Jurkat cells but also establish the pathways of the proteins as the potential therapeutic targets of leukemia.

  17. IMMUNOLOGICAL CLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIAS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2002-05-01

    Full Text Available Background. ALL is a malignant blood disease and lymphoblasts have origin in B or T lymphatic cell line. In 1997 established new World Health Organisation classification (WHO classification of malignant haematological diseases realizes the importance of cellular immunological markers (immunophenotype and chromosomal abnormalities (cytogenetics. Based on both findings we may distribute the patients in low, intermediate and high risk groups and the outcome of such distribution is risk adopted ALL treatment strategy. On Clinical department of haematology (CDH we have decided to overview immunophenotype characteristics of all ALL patients during the January 1, 1995–December 31, 2001 period.Methods and results. During the January 1, 1995–December 31, 2001 period on CDH we have treated 44 patients: 22 males and 22 females. With flow cytometer Coulter Epics XL MCS we have performed first primary antibody panel for acute leukemias antigens (CD2, CD7, CD10, CD19, CD34, cCD3, cCD13, cCD22, MPO, TdT, followed by secondary panel. The later have included antigen CD20, CD23, membrane and/or cytoplasmatic immunoglobulins or their light chains monoclonal antibodies for B-ALL and antigen CD3, CD4, CD5 and CD8 monoclonal antibodies for T-ALL subsets. Besides immunophenotyping we have evaluated all ALL patients also morphologically according to FAB classification (French-AmericanBritish classification, which is an old classification based solely on morphology.32/44 (73% patients have had immunophenotypic B-ALL, and 12/44 (27% T-ALL. Subgroups distribution of B-ALL immunophenotype were: pro-B 4/44 (9%, »common«-B 18/44 (41%, pre-B 5/44 (11.5% and mature B 5744 (11.5% and for T-ALL immunophenotype were: pro-T 2/44 (4.5%, pre-T 5/44 (11.5%, cortical-T 4/44 (9% and mature-T 1/44 (2%. Our results are quite comparable with the available data from the literature, despite the fact that newest immunological markers such as CD1a, CD79a and CD22 were not available

  18. Anti-mutagenic and Pro-apoptotic Effects of Apigenin on Human Chronic Lymphocytic Leukemia Cells

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    Mehrdad Hashemi

    2010-09-01

    Full Text Available "nDiet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line were cultured in RPMI 1640 (Sigma, supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 ºC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100. Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when expose to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P<0.01 Apoptosis was induced suitably after 48 hours by flow cytometry assay. In Ames test apigenin prevented the reverted mutations and the hindrance percent of apigenin was 98.17%.These results have revealed apigenin induced apoptosis in human lymphoma B cells in vitro.

  19. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  20. HISTORY OF ACUTE PROMYELOCYTIC LEUKEMIA: A TALE OF ENDLESS REVOLUTION

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    Francesco Lo-Coco

    2011-12-01

    Full Text Available Only few thousand people are diagnosed each year of Acute Promyelocytic Leukemia (APL worldwide. However, for a number of reasons such rare disease is regarded as a paradigm in the entire field of medicine. Once considered the most malignant human leukemia as well as the one associated with the worst prognosis, APL has been transformed in the past few decades into the most frequently curable one. This extraordinary progress has been the result of an unprecedented coincidence of advances in both biological and clinical research.

  1. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation

    Directory of Open Access Journals (Sweden)

    Kiefer Y

    2012-03-01

    Full Text Available Yvonne Kiefer1, Christoph Schulte2, Markus Tiemann2, Joern Bullerdiek11Center for Human Genetics, University of Bremen, Bremen, Germany; 2Hematopathology Hamburg, Hamburg, GermanyAbstract: Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH. Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL. Keywords: chronic lymphocytic leukemia, chromosomal abnormality, miRNA deregulation

  2. BCL11A expression in acute phase chronic myeloid leukemia.

    Science.gov (United States)

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Desch, P; Asslaber, D; Kern, D; Schnidar, H; Mangelberger, D; Alinger, B; Stoecher, M; Hofbauer, S W; Neureiter, D; Tinhofer, I; Aberger, F; Hartmann, T N; Greil, R

    2010-09-02

    The Hedgehog (Hh) pathway regulates cell proliferation and survival and contributes to tumorigenesis. We investigated the expression and function of this pathway in B-cell chronic lymphocytic leukemia (CLL) cells and in healthy B lymphocytes. Profiling of cognate Hh pathway members revealed reduced expression of two key Hh signaling effectors, Smoothened (SMOH) and GLI, in CLL cells, whereas transcription levels of other investigated members resembled normal B-lymphocyte levels. Examining the functional role of SMOH and GLI in cell survival, we found that CLL cells were hardly sensitive toward specific SMOH inhibition, but showed an unspecific decline in cell viability in response to high concentrations of the SMOH antagonist cyclopamine. In contrast, treatment with the novel GLI antagonist GANT61 reduced expression of the target gene Patched and preferentially decreased the viability of malignant cells. Specific RNA interference knockdown experiments in a CLL-derived cell line confirmed the autonomous role of GLI in malignant cell survival. GANT61-induced apoptosis in primary leukemic cells was partly attenuated by protective stromal cells, but not soluble sonic hedgehog ligand. In summary, our data show a downregulation of the classical Hh pathway in CLL and suggest an intrinsic SMOH-independent role of GLI in the ex vivo survival of CLL cells.

  4. Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells

    Science.gov (United States)

    Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

    2015-01-01

    B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process. PMID:26265439

  5. Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model

    NARCIS (Netherlands)

    Lascano, Valeria; Guadagnoli, Marco; Schot, Jan G.; Luijks, Dieuwertje M.; Guikema, Jeroen E. J.; Cameron, Katherine; Hahne, Michael; Pals, Steven; Slinger, Erik; Kipps, Thomas J.; van Oers, Marinus H. J.; Eldering, Eric; Medema, Jan Paul; Kater, Arnon P.

    2013-01-01

    Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in

  6. Enhanced formation and survival of CD4+ CD25hi Foxp3+ T-cells in chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Jak, Margot; Mous, Rogier; Remmerswaal, Ester B. M.; Spijker, René; Jaspers, Annelieke; Yagüe, Adriana; Eldering, Eric; van Lier, René A. W.; van Oers, Marinus H. J.

    2009-01-01

    Recently, it has been described that patients with chronic lymphocytic leukemia (CLL) have increased numbers of regulatory T (T(reg)) cells. In the present study, we analysed the mechanism behind T(reg) cells expansion in CLL. Neither analysis of the T-cell receptor repertoire nor CD45 isoform

  7. [PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia].

    Science.gov (United States)

    Guerra-Castillo, Francisco Xavier; Ramos-Cervantes, María Teresa; Rosel-Pech, Cecilia; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina

    2016-01-01

    In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

  8. Acute erythroid leukemia: autopsy report of a rare disease

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    Cristiane Rúbia Ferreira

    2011-12-01

    Full Text Available Acute erythroid leukemia (AEL is a rare subtype of acute myeloid leukemia(AML, characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO classification of AML defined two AEL subtypes:erythroleukaemia (EL, in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL, in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria.

  9. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  10. Early presentation of osteonecrosis in acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Mogensen, Signe Sloth; Harila-Saari, Arja; Frandsen, Thomas Leth

    2017-01-01

    Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologica......Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms...... and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy....

  11. Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

    Science.gov (United States)

    Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

    2017-01-01

    Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

  12. Diagnostic work-up of acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Sohani, Aliyah R; Bhargava, Parul; Nardi, Valentina

    2017-03-01

    Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment. © 2017 Wiley Periodicals, Inc.

  13. CDX2 gene expression in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

    2014-01-01

    CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  14. Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib.

    Science.gov (United States)

    Ivanova, Donika; Zhelev, Zhivko; Lazarova, Dessislava; Getsov, Plamen; Bakalova, Rumiana; Aoki, Ichio

    2018-03-01

    Recent studies provided convincing evidence for the anticancer activity of combined application of vitamin C and pro-vitamin K3 (menadione). The molecular pathways underlying this process are still not well established. The present study aimed to investigate the effect of the combination of vitamin C plus pro-vitamin K3 on the redox status of leukemia and normal lymphocytes, as well as their sensitizing effect for a variety of anticancer drugs. Cytotoxicity of the substances was analyzed by trypan blue staining and automated counting of live and dead cells. Apoptosis was analyzed by fluorescein isothiocyanate-annexin V test. Oxidative stress was evaluated by the intracellular levels of reactive oxygen and nitrogen species and protein-carbonyl products. Combined administration of 300 μM vitamin C plus 3 μM pro-vitamin K3 reduced the viability of leukemia lymphocytes by ~20%, but did not influence the viability of normal lymphocytes. All combinations of anticancer drug plus vitamins C and K3 were characterized by synergistic cytotoxicity towards Jurkat cells, compared to cells treated with drug alone for 24 h. In the case of barasertib and everolimus, this synergistic cytotoxicity increased within 72 hours. It was accompanied by strong induction of apoptosis, but a reduction of level of hydroperoxides and moderately increased protein-carbonyl products in leukemia cells. Leukemia lymphocytes were more sensitive to combined administration of anticancer drug (everolimus or barasertib) plus vitamins C and K3, compared to normal lymphocytes. The combination of vitamin C plus K3 seems to be a powerful redox system that could specifically influence redox homeostasis of leukemia cells and sensitize them to conventional chemotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Del(20q) in patients with chronic lymphocytic leukemia: a therapy-related abnormality involving lymphoid or myeloid cells.

    Science.gov (United States)

    Yin, C Cameron; Tang, Guilin; Lu, Gary; Feng, Xiaoli; Keating, Michael J; Medeiros, L Jeffrey; Abruzzo, Lynne V

    2015-08-01

    Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ hybridization (FISH) analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain variable region) genes, and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morphologic evidence of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia with del(20q) acquired after therapy is heterogeneous. In cases with morphologic evidence of dysplasia, the del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, the del(20q) may represent clonal evolution and disease progression. Combining morphologic analysis with FISH for del(20q) or performing FISH on immunomagnetically selected sub-populations to localize the cell population with this abnormality may help guide patient management.

  16. Sensitive DNA impedance biosensor for detection of cancer, chronic lymphocytic leukemia, based on gold nanoparticles/gold modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Ensafi, Ali A., E-mail: ensafi@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Taei, M. [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Rahmani, H.R. [Department of Animal Science, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Khayamian, T. [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of)

    2011-10-01

    Highlights: > Chronic lymphocytic leukemia causes an increase in the number of white blood cells. > We introduced a highly sensitive biosensor for the detection of chronic lymphocytic leukemia. > A suitable 25-mer ssDNA probe was immobilized on the surface of the gold nanoparticles. > We used electrochemical impedance spectroscopy as a suitable tool for the detection. > Detection of chronic lymphocytic leukemia in blood sample was checked using the sensor. - Abstract: A simple and sensitive DNA impedance sensor was prepared for the detection of chronic lymphocytic leukemia. The DNA electrochemical biosensor is worked based on the electrochemical impedance spectroscopic (EIS) detection of the sequence-specific DNA related to chronic lymphocytic leukemia. The ssDNA probe was immobilized on the surface of the gold nanoparticles. Compared to the bare gold electrode, the gold nanoparticles-modified electrode could improve the density of the probe DNA attachment and hence the sensitivity of the DNA sensor greatly. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy were performed in a solution containing 1.0 mmol L{sup -1} K{sub 3}[Fe(CN){sub 6}]/K{sub 4}[Fe(CN){sub 6}] and 50 mmol L{sup -1} phosphate buffer saline pH 6.87 plus 50 mmol L{sup -1} KCl. In the CV studied, the potential was cycled from 0.0 to +0.65 V with a scan rate of 50 mV s{sup -1}. Using EIS, the difference of the electron transfer resistance ({Delta}R{sub et}) was linear with the logarithm of the complementary oligonucleotides sequence concentrations in the range of 7.0 x 10{sup -12}-2.0 x 10{sup -7} mol L{sup -1}, with a detection limit of 1.0 x 10{sup -12} mol L{sup -1}. In addition, the DNA sensor showed a good reproducibility and stability during repeated regeneration and hybridization cycles.

  17. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    OpenAIRE

    Góes, Luccas Santos Patto de; Lopes, Roberto Iglesias; Campos, Octavio Henrique Arcos; Oliveira, Luiz Carlos Neves de; Sant’Anna, Alexandre Crippa; Dall’Oglio, Marcos Francisco; Srougi, Miguel

    2014-01-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associat...

  18. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  19. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  20. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    International Nuclear Information System (INIS)

    Soares, Maria de Fatima; Braga, Flavio Tulio; Rocha, Antonio Jose da; Lederman, Henrique Manoel

    2005-01-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  1. Leucemia congénita aguda Acute congenital leukemia

    Directory of Open Access Journals (Sweden)

    Nilvia Esther González García

    2011-06-01

    Full Text Available La leucemia aguda durante el período neonatal es poco frecuente de evolución rápida y pronóstico sombrío. Sus características clínicas y biológicas difieren de las encontradas en niños de mayor edad, y su inicio se caracteriza por afectación cutánea, hepatoesplenomegalia, hiperleucocitosis e infiltración del sistema nervioso central. Se han observado pacientes con formas tanto mieloides como linfoides, pero la leucemia mieloide aguda parece predominar en esta etapa de la vida. Se presenta el caso de un paciente con leucemia congénita clasificada morfológicamente, con aparición de manifestaciones clínicas de enfermedad hematológica desde el nacimiento y diagnóstico de leucemia linfoblástica aguda congénita.Acute leukemia during neonatal period is not frequent, of a fast course and gloomy prognosis. Its clinical and biological features differ of that present in older children and it onset is characterized by cutaneous affection, hepatosplenomegaly, hyperleukocytosis and infiltration of central nervous system (CNS. There are patients presenting with myeloid and lymphoid types, but the acute leukemia seems to predominate in this stage of life. This is the case of a patient with acute leukemia morphologically classified, with appearance of clinical manifestations of hematologic disease from birth and a diagnosis of congenital acute lymphoblastic leukemia.

  2. Flowcytometric Immunophenotypic Profile of Acute Leukemia: Mansoura Experience

    OpenAIRE

    Salem, Dalia A.; Abd El-Aziz, Sherin M.

    2011-01-01

    Acute leukemia (AL) displays characteristic patterns of antigen expression, which facilitate their identification and proper classification. The purpose of this study is to evaluate the diagnostic usefulness of commonly used immune-markers for immunophenotyping of AL and to define the best immune-markers to be used for proper diagnosis and classification of AL. Besides, to recognize the frequency of different AL subtypes and the antigen expression profile in our Egyptian patients. We retrospe...

  3. Elbow septic arthritis associated with pediatric acute leukemia: a case report and literature review.

    Science.gov (United States)

    Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki

    2015-01-01

    Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.

  4. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  5. Relations between the stimulation of mixed lymphocyte populations and the staging system according Rai in patients with chronic lymphatic leukemia

    International Nuclear Information System (INIS)

    Heilmann, E.; Venne, U.

    1979-01-01

    By means of the incorporation rate of 3 H thymidine into the lymphocytes of patients with chronic lymphatic leukemia the possibility of stimulating them by using different mitogens was checked and compared with normal persons. The examination covered 11 patients treated with extracorporeal irradiation of the blood (ECIB), 5 patients treated with a chlorambucil therapy, and 10 untreated patients who where classified according to the staging system proposed by Rai. The lymphocytes of the peripheral blood were stimulated as mixed and isolated T and B-lymphocytes in the microculture by using the mitogens PHA, PWM, ConA, and LPS. In all CLL patients there was a diminished stimulation rate of a mixed lymphocyte population. A relation existed between the seriousness of the stage and the deminution of the incorporation rate of 3 H thymidine. A corresponding correlation could not be identified in untreated CLL patients. Isolated T-lymphocytes revealed better results of stimulation than the total population. As to their function B-lymphocytes showed a dependence on the kind of therapy. In the mixed lymphocyte culture of normal persons the best findings could be observed after stimulation with PHA, that is also valid for CLL patients. PHA, PWA, ConA, and LPS were suitable as substances stimulating B-lymphocytes with different efficacy in normal persons and CLL patients. Both collectives showed the best results in the T-lymphocyte culture after stimulation with LPS. (author)

  6. Diagnosis of acute myeloid leukemia in a dental hospital; report of a ...

    African Journals Online (AJOL)

    2014-10-10

    Oct 10, 2014 ... [1]. Acute myeloid leukemia (AML) can present as leukemic infiltrates in many sites including gingival enlargement, mucosal and skin nodules.[5] Oral lesions occur both in acute and chronic forms of all types of leukemias, however, oral manifestations are more common in the acute stages of the disease.

  7. No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Vasan, Senthil K

    2015-01-01

    Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL...... occurrence among 7413 recipients of blood from 796 donors diagnosed with CLL after donation cessation, and among 80, 431 recipients of blood from 7477 matched CLL-free donors. During follow-up, 12 and 107 cases of CLL occurred among the exposed and unexposed recipients, respectively, yielding a relative risk...... of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries' entire computerized...

  8. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Agathangelidis, Andreas; Darzentas, Nikos; Hadzidimitriou, Anastasia

    2012-01-01

    Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency...... as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may...... be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR...

  9. Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen; Hanna, B.; Ohl, S.

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is an incurable malignancy of mature B cells. One of the major challenges in treatment of CLL is the achievement of a complete remission to prevent relapse of disease originating from cells within lymphoid tissues and subsequent chemoresistance. In search...... for novel drugs that target CLL cells also in protective microenvironments, we performed a fungal extract screen using cocultures of primary CLL cells with bone marrow-derived stromal cells. A metabolite produced by Penicillium aquamarinium was identified as Chaetoglobosin A, a member of the cytochalasan...... family that showed preferential induction of apoptosis in CLL cells, even under culture conditions that mimic lymphoid tissues. In vitro testing of 89 CLL cases revealed effective targeting of CLL cells by Chaetoglobosin A, independent of bad prognosis characteristics, like 17p deletion or TP53 mutation...

  10. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Hadeel M. Aljafar

    2015-10-01

    Full Text Available Otologic manifestations in chronic lymphocytic leukemia (CLL are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhagic bullae on the posterior segment of tympanic membrane. Left sided facial paralysis developed on the third day of admission. Full recovery of facial paralysis is achieved by 10 days course of corticotherapy. Histological examination of middle ear tissue biopsy showed infiltration by monotonous small lymphoid cells, showing round nuclei, condensed chromatin suggestive of CLL. Although rare, unusual otologic manifestations should raise the suspicion of a temporal bone metastasis as a sign of relapsing CLL.

  11. Recurrent Malignant Melanoma Presenting as Isolated Pleural Metastases in a Patient with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Kartik Anand

    2017-01-01

    Full Text Available Isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma. We report an unusual case of a patient with chronic lymphocytic leukemia (CLL and recurrent pleural effusions. The pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of CLL. However, chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. A video-assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma. Our case underlines the importance of having a suspicion for secondary causes of effusion in patients with CLL. We briefly discuss the mechanisms of an increased incidence of secondary cancers in CLL and the diagnosis of isolated pleural metastases in malignant melanoma.

  12. Familial chronic lymphocytic leukemia in Norway and Denmark. Comments on pleiotropy and birth order.

    Science.gov (United States)

    Jønsson, Viggo; Tjønnfjord, Geir E; Johannesen, Tom B; Ly, Bernt; Olsen, Jørgen H; Yuille, Martin

    2010-01-01

    To investigate the genetics of chronic lymphocytic leukemia (CLL). In 56 (7%) out of 800 CLL patients with concomitant malignant hematological disease, 51 families and 141 cases were ascertained. 106 cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of myeloproliferative disorders. Paternal disease was transmitted primarily to the youngest sons in the sibship while maternal disease was transmitted equally to all sibs, demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order (maternal-offspring combination: relative risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell expression in familial and sporadic CLL was indistinguishable. Parental genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.

  13. EFFECTIVENESS OF VENETOСLAX IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (LITERATURE REVIEW

    Directory of Open Access Journals (Sweden)

    V. V. Strugov

    2017-01-01

    Full Text Available Currently we are facing a revolution in therapy of chronic lymphocytic leukemia, related to the development of novel target drugs, which have markedly improved treatment results in all groups of patients. While inhibitors of Bruton’s tyrosine kinase (ibrutinib, acalabrutinib etc. and phosphatidylinositol-3 kinase isoforms (idelalisib, umbralisib etc. are currently in the spotlight, much less attention is paid to antiapoptotic protein inhibitors such as venetoclax. In this review we summarize the results of venetoclax clinical studies in CLL as monotherapy and in combinations. The drug is distinguished by a high rate of complete responses and minimal residual disease eradication in high risk CLL patients, as well as a favorable toxicity profile. This makes it an ideal component of non-genotoxic regimens, aimed at the cure of the disease.

  14. A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria.

    Science.gov (United States)

    Margolskee, Elizabeth; Mikita, Geoff; Rea, Bryan; Bagg, Adam; Zuo, Zhuang; Sun, Yi; Goswami, Maitrayee; Wang, Sa A; Oak, Jean; Arber, Daniel A; Allen, M Brandon; George, Tracy I; Rogers, Heesun J; Hsi, Eric; Hasserjian, Robert P; Orazi, Attilio

    2018-02-05

    The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid

  15. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

    Czech Academy of Sciences Publication Activity Database

    Kanderová, V.; Kuzilkova, D.; Stuchlý, J.; Vašková, M.; Brdička, Tomáš; Fišer, K.; Hrušák, O.; Lund-Johansen, F.; Kalina, T.

    2016-01-01

    Roč. 15, č. 4 (2016), s. 1246-1261 ISSN 1535-9476 R&D Projects: GA MŠk 2B06064 Institutional support: RVO:68378050 Keywords : acute lymphoblastic-leukemia * acute promyelocytic leukemia * cytometric immunobead assay * caspase-dependent cleavage * acute myeloid-leukemia * gene-expression * fusion proteins * flow-cytometry * pcr data * b-cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.540, year: 2016

  16. A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Tucker DL

    2015-06-01

    Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

  17. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    Science.gov (United States)

    2018-04-02

    Glioma; Lymphoma; Metastatic Malignant Solid Neoplasm; Neuroendocrine Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Breast Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Prostate Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Solid Neoplasm

  18. Cellulitis with Leukocytopenia as an Initial Sign of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Sachiko Sakamoto

    2012-03-01

    Full Text Available Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3 is caused by translocation of reciprocal chromosomal rearrangement t(15;17, which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia.

  19. Survival and Clinical Aspects for Patients with Chronic Lymphocytic Leukemia in Kermanshah, Iran.

    Science.gov (United States)

    Payandeh, Mehrdad; Sadeghi, Edris; Sadeghi, Masoud

    2015-01-01

    Chronic lymphocytic leukemia (CLL)is the most common leukemia in adults in Western countries but is relatively rare in Asia. Immune hemolytic anemia, Evan's syndrome, lymphadenopathy, organomegaly and B symptoms are the main complaints of patients in CLL. The present retrospective analysis evaluated a group of 109 patients with CLL over a 9-year period, studying correlations between sex, age and overall survival. The patients were hospitalized in the Clinic of Hematology and Oncology, Kermanshah, Iran, between 2006 and 2014. Data analysis for sex and age was performed using IBM SPSS19 and overall survival was plotted by Kaplan- Meier plot, Log-rank test in Graph Pad prism 5 Software for five-year periods. The mean age of diagnosis for CLL patients was 60.73 years, 59.6% male. Survival rate patients was 64% and mean overall survival was 38.5 months. In the Rai system, fourteen patients (12.8%) had stage III and twenty eight patients (25.7%) had stage IV. Most frequent clinical features in patients with CLL were lymphadenopathy (38.7%) and organomegaly (34%), respectively. There is not relationship between sex and age in patients but overall survival rate in females was higher than in males. In Asian countries, CLL is more in male and in age above 60 years. Complaints about lymphadenopathy and virus infection are prevalent.

  20. Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in Japanese chronic lymphocytic leukemia cases

    Directory of Open Access Journals (Sweden)

    Imajoh Masayuki

    2012-06-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9, another lymphotropic polyomavirus, in Japanese CLL cases. Findings We found that 9/27 CLL cases (33.3 % were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. Conclusions This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.

  1. Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic leukemia cells to prednisolone and cytarabine.

    Science.gov (United States)

    Czyzewski, Krzysztof; Zaborowska, Agnieszka; Styczyński, Jan

    2006-01-01

    Thalidomide is a derivative of glutamic acid with anti-angiogenic, anti-inflammatory, immunomodulatory and anti-cancer properties that was found to inhibit the production of tumor necrosis factor alpha in vitro, stimulate reactive oxygen species production, and inhibit vascular endothelial growth factor receptor in acute leukemias. The purpose of this study was to determine the in vitro activity of thalidomide as a single agent and in combination with prednisolone or cytarabine in childhood acute lymphoblastic leukemia (ALL). Bone marrow samples of 40 childhood ALL patients, normal lymphocytes of 9 healthy adults, and 3 lymphoid cell lines were evaluated for cytotoxicity of thalidomide (alone and in combination with prednisolone and cytarabine) using the MTT assay. Cell cycle analysis was performed by flow cytometry. Thalidomide as a single agent had weak antileukemic activity to the childhood ALL samples. However, in the presence of thalidomide the cytotoxicities of prednisolone and cytarabine were increased 3.3-fold (p<0.001) and 2.7-fold (p=0.002), respectively. Thalidomide increased apoptosis in lymphoblasts and modulated the cell-cycle arrest caused by prednisolone, but not that by cytarabine, in childhood ALL samples. Thalidomide increases in vitro the sensitivity of childhood ALL cells to prednisolone and cytarabine.

  2. Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Tatsuki; Tomonaga, Masao; Bennett, J.M. and others

    1988-06-01

    The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85 % agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2 %. The present study suggest that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

  3. Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia

    International Nuclear Information System (INIS)

    Matsuo, Tatsuki; Tomonaga, Masao; Bennett, J.M.

    1988-01-01

    The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85 % agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2 %. The present study suggest that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure. (author)

  4. Richter syndrome in chronic lymphocytic leukemia: updates on biology, clinical features and therapy.

    Science.gov (United States)

    Jamroziak, Krzysztof; Tadmor, Tamar; Robak, Tadeusz; Polliack, Aaron

    2015-07-01

    Richter syndrome (RS) or Richter transformation is the development of secondary aggressive lymphoma in the setting of underlying chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most frequently CLL transforms into diffuse large B-cell lymphoma (DLBCL) (90%) and rarely (10%) into Hodgkin lymphoma, termed Hodgkin variant of Richter syndrome (HvRS). RS is generally characterized by an aggressive clinical course and poor prognosis. In recent years, major advances have been made in understanding genetic events which relate to the progression of CLL or transformation into RS. Better understanding of the molecular pathways has revealed that RS is not a single homogeneous entity. The majority of cases are clonally related to the original CLL clone, while a minority develop from an unrelated clone. This review summarizes new data relating to the molecular biology and the genetic/epigenetic changes occurring during Richter transformation, and also considers the clinical features and therapy for both DLBCL-RS and Hodgkin variant-RS.

  5. Diffuse pulmonary infiltrates in an old man with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Alireza Hosseinnezhad

    2011-05-01

    Full Text Available An 82-year-old man known case of chronic lymphocytic leukemia (CLL presented with fever and weakness. He had never received any treatment for his CLL in the past. On admission he was found to be in mild respiratory distress with bilateral crackles and had markedly elevated white blood count (WBC (137 K/uL with 93% lymphocytes. His respiratory status deteriorated necessitating noninvasive ventilatory support. Chest computed tomography (CT scan revealed bilateral diffuse ground glass opacities, so broad spectrum antibiotic therapy was initiated. Despite that, he remained febrile and cultures were all negative. Chest x-rays showed progressive worsening of diffuse alveolar opacities. Bronchoalveolar lavage (BAL was negative for infectious etiologies, however flow cytometry of the fluid was consistent with CLL. Chemotherapy with chlorambucil was started. Although most of the pulmonary infiltrates in CLL patients are due to infectious causes, leukemic cells infiltration should be considered as well in CLL patients with respiratory symptoms who do not respond appropriately to standard antimicrobial regimen.

  6. Genetic abnormalities in chronic lymphocytic leukemia and their clinical and prognostic implications.

    Science.gov (United States)

    Dierlamm, J; Michaux, L; Criel, A; Wlodarska, I; Van den Berghe, H; Hossfeld, D K

    1997-03-01

    Clonal chromosome abnormalities can be detected in approximately 50% of patients with chronic lymphocytic leukemia (CLL). The most common changes are trisomy 12, followed by structural abnormalities of 13q, 11q, 6q, and 14q. By fluorescence in situ hybridization (FISH), these aberrations can be demonstrated even in cases with insufficient mitotic yield or a normal karyotype. The biologic consequences of trisomy 12 are unknown, but a gene dosage effect is suspected and studies on partial trisomy 12 indicate that the region 12q13 to 12q22 might be of particular pathogenetic importance. Trisomy 12 is strongly associated with atypical lymphocyte morphology and seems to be a secondary event in leukemogenesis, as shown by combined immunophenotyping and interphase FISH. Structural abnormalities of 13q frequently involve hetero- and homozygous deletions of a region in 13q14, distal to the retinoblastoma gene, which may be the site of a tumor suppressor gene. In contrast to a normal karyotype or structural changes of 13q, complex karyotypic abnormalities, high percentage of abnormal metaphases, trisomy 12 and structural changes involving the P53 tumor suppressor gene on 17p13 are adverse prognostic indicators. Cytogenetic and molecular findings provide important diagnostic, clinical, and prognostic information which can contribute to treatment decisions and follow-up of CLL patients.

  7. Differentiation of chronic lymphocytic leukemia B cells into immunoglobulin secreting cells decreases LEF-1 expression.

    Directory of Open Access Journals (Sweden)

    Albert Gutierrez

    Full Text Available Lymphocyte enhancer binding factor 1 (LEF-1 plays a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia (CLL cells aberrantly express LEF-1 and its expression is required for cellular survival. We hypothesized that modification of the differentiation status of CLL cells would result in loss of LEF-1 expression and eliminate the survival advantage provided by its aberrant expression. In this study, we first established a methodology that induces CLL cells to differentiate into immunoglobulin (Ig secreting cells (ISC using the TLR9 agonist, CpG, together with cytokines (CpG/c. CpG/c stimulation resulted in dramatic CLL cell phenotypic and morphologic changes, expression of cytoplasmic Ig, and secretion of light chain restricted Ig. CpG/c stimulation also resulted in decreased CLL cell LEF-1 expression and increased Blimp-1 expression, which is crucial for plasma cell differentiation. Further, Wnt pathway activation and cellular survival were impaired in differentiated CLL cells compared to undifferentiated CLL cells. These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation.

  8. Behavioral treatment of night terrors in a child with acute leukemia.

    Science.gov (United States)

    Kellerman, J

    1979-03-01

    A 3-year-old girl diagnosed with acute lymphocytic leukemia presented with a 1-month history of recurrent nightmares. Symptoms of the disturbance conformed to a clinical picture of slow wave arousal night terrors, or pavor nocturnus. Behavioral treatment aimed at reducing anxiety related to maternal separation and medical procedures, and at reinforcing appropriate sleep patterns was effective in reducing and eventually eliminating the symptoms. Follow-up revealed no return of nightmares or existence of new problems. A brief review of descriptive, etiological and treatment aspects of night terrors is presented and the hypothesis is put forth that such episodes represent a psychological reaction to trauma. The importance of being aware of age variables in the expression of children's anxiety is noted as is the value of careful tabulation of outcome data.

  9. Metaphyseal impaction fractures in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Manson, D.; Cockshott, W.P.; Martin, R.F.

    1989-01-01

    Patients with acute lymphatic leukaemia frequently are osteoporotic. A small subset of these develop disabling metaphyseal transverse fractures, usually bilateral and in the lower limb. These impaction fractures have a characteristic appearance and develop in recently laid down bone. They may develop ab initio of during therapy, Magnesium deficiency is found in these patients.

  10. Role of rituximab in first-line treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Jeffrey Bryan

    2010-12-01

    Full Text Available Jeffrey Bryan, Gautam BorthakurDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Chronic lymphocytic leukemia (CLL is a biologically heterogeneous illness that primarily afflicts the elderly. For many decades, the initial therapy for most patients requiring treatment was limited to single-agent alkylator therapy. Within the last two decades, we have seen remarkable progress in understanding the biology of CLL and the development of more effective treatment strategies that have employed monoclonal antibodies, such as rituximab (anti-CD20. Furthermore, recognition of the synergy between fludarabine, cyclophosphamide, and rituximab (FCR prompted investigators to explore the clinical activity of FCR in Phase II and III trials in patients with relapsed/refractory or previously untreated CLL. On the basis of these findings, the US Food and Drug Administration (FDA recently approved rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed/refractory or previously untreated CD20-postive CLL. Recent data from a randomized Phase III trial has confirmed improved overall survival with FCR in patients with previously untreated CLL. However, FCR is not for everyone. More tolerable regimens using rituximab for the elderly and less fit patients are being pursued in clinical trials. Recent Phase II trials have explored potentially less myelosuppressive approaches by using lower doses of fludarabine and cyclophosphamide, replacing fludarabine with pentostatin, and combining rituximab with chlorambucil. Furthermore new biomarkers predictive of early disease progression have prompted investigators to explore the benefits of early treatment with rituximab combined with other agents. In addition to the proven utility of rituximab as a frontline agent for CLL, rituximab has a favorable toxicity profile both as a single agent and in combination with chemotherapy. The

  11. Novel somatic mutations in large granular lymphocytic leukemia affecting the STAT-pathway and T-cell activation

    International Nuclear Information System (INIS)

    Andersson, E I; Rajala, H L M; Eldfors, S; Ellonen, P; Olson, T; Jerez, A; Clemente, M J; Kallioniemi, O; Porkka, K; Heckman, C; Loughran, T P Jr; Maciejewski, J P; Mustjoki, S

    2013-01-01

    T-cell large granular lymphocytic (T-LGL) leukemia is a clonal disease characterized by the expansion of mature CD3+CD8+ cytotoxic T cells. It is often associated with autoimmune disorders and immune-mediated cytopenias. Our recent findings suggest that up to 40% of T-LGL patients harbor mutations in the STAT3 gene, whereas STAT5 mutations are present in 2% of patients. In order to identify putative disease-causing genetic alterations in the remaining T-LGL patients, we performed exome sequencing from three STAT mutation-negative patients and validated the findings in 113 large granular lymphocytic (LGL) leukemia patients. On average, 11 CD8+ LGL leukemia cell-specific high-confidence nonsynonymous somatic mutations were discovered in each patient. Interestingly, all patients had at least one mutation that affects either directly the STAT3-pathway (such as PTPRT) or T-cell activation (BCL11B, SLIT2 and NRP1). In all three patients, the STAT3 pathway was activated when studied by RNA expression or pSTAT3 analysis. Screening of the remaining 113 LGL leukemia patients did not reveal additional patients with same mutations. These novel mutations are potentially biologically relevant and represent rare genetic triggers for T-LGL leukemia, and are associated with similar disease phenotype as observed in patients with mutations in the STAT3 gene

  12. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

    2009-11-15

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

  13. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Forester, Craig M.; Braunreiter, Chi L.; Yaish, Hasan; Afify, Zeinab; Hedlund, Gary L.

    2009-01-01

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

  14. Haploidentical Transplantation in Children with Acute Leukemia: The Unresolved Issues

    Directory of Open Access Journals (Sweden)

    Sarita Rani Jaiswal

    2016-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT remains a curative option for children with high risk and advanced acute leukemia. Yet availability of matched family donor limits its use and although matched unrelated donor or mismatched umbilical cord blood (UCB are viable options, they fail to meet the global need. Haploidentical family donor is almost universally available and is emerging as the alternate donor of choice in adult patients. However, the same is not true in the case of children. The studies of haploidentical HSCT in children are largely limited to T cell depleted grafts with not so encouraging results in advanced leukemia. At the same time, emerging data from UCBT are challenging the existing paradigm of less stringent HLA match requirements as perceived in the past. The use of posttransplantation cyclophosphamide (PTCY has yielded encouraging results in adults, but data in children is sorely lacking. Our experience of using PTCY based haploidentical HSCT in children shows inadequacy of this approach in younger children compared to excellent outcome in older children. In this context, we discuss the current status of haploidentical HSCT in children with acute leukemia in a global perspective and dwell on its future prospects.

  15. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

    Science.gov (United States)

    Zwaan, C Michel; Kolb, Edward A; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S J M; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E S; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C; Rizzari, Carmelo; Rubnitz, Jeffrey E; Smith, Owen P; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M; Creutzig, Ursula; Kaspers, Gertjan J L

    2015-09-20

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. © 2015 by American Society of Clinical Oncology.

  16. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Zwaan, C. Michel; Kolb, Edward A.; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S.J.M.; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E.S.; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C.; Rizzari, Carmelo; Rubnitz, Jeffrey E.; Smith, Owen P.; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M.; Creutzig, Ursula; Kaspers, Gertjan J.L.

    2015-01-01

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML—supportive care—and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

  17. Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Price KE

    2013-08-01

    Full Text Available Kimberly E Price, Najma Saleem, Georgina Lee, Michael SteinbergMassachusetts College of Pharmacy and Health Sciences University, Worcester, MA, USAAbstract: Development of BCR-ABL tyrosine kinase inhibitors (TKIs have improved outcomes for patients diagnosed with chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. However, resistance or intolerance to these TKIs still leaves some patients without many treatment options. One point mutation in particular, the T315I mutation, has been shown to be resistant to first and second generation TKIs. The third generation TKI, ponatinib, may provide an option for these patients. Ponatinib (Iclusig®, an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. A Phase II study evaluated ponatinib in patients who were resistant or intolerant to nilotinib or dasatinib or patients who had the T315I mutation. In the Phase II study, ponatinib produced a major cytogenetic response in 54% of chronic phase chronic myeloid leukemia patients. It further achieved major hematologic response in 52% of patients in the accelerated phase, 31% of patients in the blast phase, and 41% of Philadelphia chromosome positive acute lymphoblastic leukemia patients. Ponatinib also showed efficacy in patients with the T315I mutation. Serious adverse events included arterial thrombosis, hepatotoxicity, cardiovascular risks, pancreatitis, hemorrhage, fluid retention, myelosuppression, rash, abdominal pain, and embryo–fetal toxicity. Due to the risk of these adverse events and potential drug interactions, the use of ponatinib must be carefully weighed against the benefits in treating patients who have limited treatment options.Keywords: BCR-ABL, tyrosine kinase inhibitor, TKI, T315I, Philadelphia chromosome

  18. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  19. The Diagnostic Value of Flow Cytometry Imunophenotyping in an Albanian Patient Population with a Preliminary Clinical Diagnosis of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Valentina Semanaj

    2014-03-01

    Conclusion: Flow cytometry immunophenotyping is a fundamental examination for the final diagnosis of chronic lymphocytic leukemia. The expression of CD38+ in CLL patients stands for a more advanced clinical stage.

  20. The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia.

    Science.gov (United States)

    Balgobind, B V; Zwaan, C M; Pieters, R; Van den Heuvel-Eibrink, M M

    2011-08-01

    Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

  1. The Human CD38 Monoclonal Antibody Daratumumab Shows Antitumor Activity and Hampers Leukemia-Microenvironment Interactions in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Matas-Céspedes, Alba; Vidal-Crespo, Anna; Rodriguez, Vanina; Villamor, Neus; Delgado, Julio; Giné, Eva; Roca-Ho, Heleia; Menéndez, Pablo; Campo, Elías; López-Guillermo, Armando; Colomer, Dolors; Roué, Gaël; Wiestner, Adrian; Parren, Paul W H I; Doshi, Parul; van Bueren, Jeroen Lammerts; Pérez-Galán, Patricia

    2017-03-15

    Purpose: To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38 + chronic lymphocytic leukemia (CLL) subtype. Experimental Design: The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP), or human serum to analyze complement-dependent cytotoxicity (CDC). The effect of daratumumab on CLL cell migration and adhesion to extracellular matrix was characterized. Daratumumab activity was validated in two in vivo models. Results: Daratumumab demonstrated efficient lysis of patient-derived CLL cells and cell lines by ADCC in vitro and ADCP both in vitro and in vivo whereas exhibited negligible CDC in these cells. To demonstrate the therapeutic effect of daratumumab in CLL, we generated a disseminated CLL mouse model with the CD38 + MEC2 cell line and CLL patient-derived xenografts (CLL-PDX). Daratumumab significantly prolonged overall survival of MEC2 mice, completely eliminated cells from the infiltrated organs, and significantly reduced disease burden in the spleen of CLL-PDX. The effect of daratumumab on patient-derived CLL cell dissemination was demonstrated in vitro by its effect on CXCL12-induced migration and in vivo by interfering with CLL cell homing to spleen in NSG mice. Daratumumab also reduced adhesion of CLL cells to VCAM-1, accompanied by downregulation of the matrix metalloproteinase MMP9. Conclusions: These unique and substantial effects of daratumumab on CLL viability and dissemination support the investigation of its use in a clinical setting of CLL. Clin Cancer Res; 23(6); 1493-505. ©2016 AACR . ©2016 American Association for Cancer Research.

  2. Immunophenotype and increased presence of CD4+CD25+ regulatory T cells in patients with acute lymphoblastic leukemia

    OpenAIRE

    WU, CUI-PING; QING, XI; WU, CUI-YUN; ZHU, HONG; ZHOU, HAI-YAN

    2011-01-01

    Acute lymphoblastic leukemia (ALL), cancer of the white blood cells, is a heterogeneous disease that mainly occurs due to the malignant cloning of original and naive lymphocytes. The aim of this study was to explore the immunophenotype, the percentage of CD4+CD25+ regulatory T cells (Tregs) and the expression of cytokines interleukin (IL)-2, IL-10 and TGF-β in patients with ALL. The immunophenotype and levels of CD4+CD25+ Tregs were detected using flow cytometry in the peripheral blood of 35 ...

  3. Brief communication: evidence that B lymphocytes carry the nuclear pocket abnormality associated with bovine leukemia virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, K.A.; Paul, P.S.; Weber, A.F.; Sorensen, D.K.; Johnson, D.W.

    1976-01-01

    Peripheral blood lymphocytes from three cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin and the frequency of lymphocytic nuclear pockets in each subpopulation were then determined. In each case the adherent population consisted predominantly of B cells with an increased nuclear pocket frequency while the non-adherent cells were 98 to 99 percent surface immunoglobulin negative and contained essentially no nuclear pockets. These findings provide additional evidence that the B subpopulation of cells is highly involved in bovine leukemia oncogenesis.

  4. Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy

    OpenAIRE

    Mohammad Shahjahani; Elham Khodadi; Mohammad Seghatoleslami; Javad Mohammadi Asl; Neda Golchin; Zeynab Deris Zaieri; Najmaldin Saki

    2015-01-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important diagnostic tools in diagnosis, classification and prognosis in acute myeloid leukemias. Based on World Health Organization (WHO) classification, acute myeloid leukemias can be divided to four groups. Due to...

  5. Chronic lymphocytic leukemia of Emu-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression

    NARCIS (Netherlands)

    Enzler, Thomas; Kater, Arnon P.; Zhang, Weizhou; Widhopf, George F.; Chuang, Han-Yu; Lee, Jason; Avery, Esther; Croce, Carlo M.; Karin, Michael; Kipps, Thomas J.

    2009-01-01

    Results of heavy-water labeling studies have challenged the notion that chronic lymphocytic leukemia (CLL) represents an accumulation of noncycling B cells. We examined leukemia cell turnover in Emu-TCL1 transgenic (TCL1-Tg) mice, which develop a CLL-like disease at 8 to 12 months of age. We found

  6. Data quality in the Danish National Acute Leukemia Registry: A Hematological Data Resource

    DEFF Research Database (Denmark)

    Østgaard, L.S.G.; Nørgaard, J.M.; Severinsen, Marianne Tang

    2013-01-01

    The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data.......The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data....

  7. Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma

    DEFF Research Database (Denmark)

    Hansen, P B; Kjeldsen, L; Dalhoff, K

    1992-01-01

    Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic...

  8. Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate

    DEFF Research Database (Denmark)

    Abrahamsson, Jonas; Forestier, Erik; Heldrup, Jesper

    2011-01-01

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.......To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course....

  9. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  10. New vessel formation and aberrant VEGF/VEGFR signaling in acute leukemia : Does it matter?

    NARCIS (Netherlands)

    De Bont, ESJM; Neefjes, VME; Rosati, S; Vellenga, E; Kamps, WA

    2002-01-01

    Although many patients with acute leukemia achieve a hematological complete remission with aggressive intensive therapy protocols, a large proportion shows reoccurrence of disease. Novel strategies are warranted. In acute leukemia new vessel formation is observed. New vessel formation is the result

  11. Direct and indirect targeting of MYC to treat acute myeloid leukemia

    OpenAIRE

    Kogan, Scott; Goga, Andrei; Brondfield, S; Brondfield, S; Umesh, S; Umesh, S; Corella, A; Corella, A; Zuber, J; Rappaport, AR; Rappaport, AR; Gaillard, C

    2015-01-01

    © 2015 The Author(s) Purpose: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is often resistant to conventional therapies. The MYC oncogene is commonly overexpressed in AML but has remained an elusive target. We aimed to exami

  12. Diagnosis of acute myeloid leukemia in a dental hospital; report of a ...

    African Journals Online (AJOL)

    Acute myeloid leukemias (AMLs) are aggressive hematopoietic neoplasms that, if untreated, can lead to death within days. Owing to its high morbidity rate, early diagnosis and appropriate medical therapy is essential. Oral lesions may be the presenting feature of acute leukemias and are, therefore, important diagnostic ...

  13. Diagnostic imaging of limbs in children with acute leukemia

    International Nuclear Information System (INIS)

    Song Yingru; Li Chenhui; Li Guo; Ye Wei; Huang Zhongkui; Long Liling; Luo Jianming

    2011-01-01

    Objective: To evaluate X-ray and MRI features of limbs in childhood acute leukemia. Methods: Thirteen children with acute leukemia in our pediatric hematology ward were recruited. All patients were pathologically diagnosed by bone marrow aspiration and complained of bone or joint pain in the first visit. Conventional X-ray and MRI examinations of algesic sites were performed before clinical treatment and after complete remission. MR images were obtained with SE-T 1 WI, SE-T 2 WI and T 2 WI-fat suppressed sequences and symmetrical bilateralism was requested while scanning. X-ray and MRI manifestations were evaluated and compared. Results: All 13 patients had received X-ray examinations. Among them, 6 had normal X-ray findings, whereas the other 7 (14 sites) showed various abnormalities including radiolucent metaphyseal bands (5 sites), periosteal reaction (3 sites), osteapenia (2 sites), mixed lesions (lysis- sclerosis, 1 site), and permeative pattern (3 sites). The number of patients for MRI examinations was 8 (11 sites). Among them, 6 (9 sites) showed bone marrow infiltration and bone marrow necrosis accompanied by normal X-ray findings, another 2 (2 sites) showed bone marrow infiltration associated with radiographic abnormalities of periosteal reaction and radiolucent metaphyseal bands. Four cases were followed up within 1 week when reached complete remission by chemotherapy. MR images features included reduced sizes of bone marrow infiltration lesions associated with increased signal intensity on T 1 WI, and disappearance of double-line sign on bone marrow necrosis accompanied by signal homogenization. However, the radiograph before and after treatment in the same cases did not differ significantly. Conclusions: MRI was earlier and more comprehensive in showing limbs bone marrow abnormality than radiogram in acute leukemia children with chief complaint of osteoarticular pains. MRI might be one of indicators in following up therapeutic effect for AL children with

  14. Increased regulatory T cells in acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Idris, Siti-Zuleha; Hassan, Norfarazieda; Lee, Le-Jie; Md Noor, Sabariah; Osman, Raudhawati; Abdul-Jalil, Marsitah; Nordin, Abdul-Jalil; Abdullah, Maha

    2015-10-01

    Regulation in adaptive immune response balances a fine line that prevents instigation of self-damage or fall into unresponsiveness permitting abnormal cell growth. Mechanisms that keep this balance in check include regulatory T cells (Tregs). Tregs consist of a small but heterogeneous population which may be identified by the phenotype, CD3+CD4+CD25+CD127-. Role of Tregs in pathogenesis of cancers is thus far supported by evidence of increased Tregs in various cancers and may contribute to poorer prognosis. Tregs may also be important in acute leukemias. A review of the literature on Tregs in acute leukemias was conducted and Tregs were determined in B-cell acute lymphoblastic leukemias (ALLs). Studies on Tregs in B-cell ALL are few and controversial. We observed a significantly increased percentage of Tregs (mean ± SD, 9.72 ± 3.79% vs. 7.05 ± 1.74%; P = 0.047) in the bone marrow/peripheral blood of ALL (n = 17) compared to peripheral blood of normal controls (n = 35). A positive trend between Tregs and age (R = 0.474, P = 0.055, n = 17) implicates this factor of poor prognosis in B-cell ALL. Tregs in cancer are particularly significant in immunotherapy. The manipulation of the immune system to treat cancer has for a long time ignored regulatory mechanisms inducible or in place. In lymphoma studies tumor-specific mechanisms that are unlike conventional methods in the induction of Tregs have been hypothesized. In addition, tumor-infiltrating Tregs may present different profiles from peripheral blood pictures. Tregs will continue to be dissected to reveal their mysteries and their impact on clinical significance.

  15. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

  16. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

    DEFF Research Database (Denmark)

    Sutton, Lesley-Ann; Young, Emma; Baliakas, Panagiotis

    2016-01-01

    We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations...... subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s)....

  17. Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia

    OpenAIRE

    Hatswell, Anthony J.; Thompson, Gwilym J.; Maroudas, Penny A.; Sofrygin, Oleg; Delea, Thomas E.

    2017-01-01

    Background Ofatumumab (Arzerra?, Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9?months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. Methods The objective of the study was to present a metho...

  18. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    Science.gov (United States)

    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko

    2015-01-01

    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  19. Comorbidity and performance status in acute myeloid leukemia patients

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, J M; Sengeløv, H

    2015-01-01

    As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and World Health Organization Performance Status (...... with an increased short- and long-term mortality (adjusted 90 day MR, PS⩾2=3.43 (95%CI=2.30-5.13); adjusted 91 day-3 year MR=1.35 (95%CI=1.06-1.74)). We propose that more patients with comorbidity may benefit from intensive chemotherapy....

  20. Complexity on Acute Myeloid Leukemia mRNA Transcript Variant

    Directory of Open Access Journals (Sweden)

    Carlo Cattani

    2011-01-01

    Full Text Available This paper deals with the sequence analysis of acute myeloid leukemia mRNA. Six transcript variants of mlf1 mRNA, with more than 2000 bps, are analyzed by focusing on the autocorrelation of each distribution. Through the correlation matrix, some patches and similarities are singled out and commented, with respect to similar distributions. The comparison of Kolmogorov fractal dimension will be also given in order to classify the six variants. The existence of a fractal shape, patterns, and symmetries are discussed as well.

  1. Features of children temperament with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    N. A. Kornetov

    2013-01-01

    Full Text Available The temperament characteristics were studied in 86 children with acute lymphoblastic leukemia (ALL at the age of 3–16 years. Research was conducted using standardized and adapted to the Russian-speaking population of parental questionnaires for children of different age groups (Kolpakov V.G. et al., 1993. Statistically significant differences in temperament ALL patients from healthy children installed and feature of temperament, which is most often seen in children with conduct disorder are installed. The need for psychological and/or psychiatric counseling this category of patients is substantiated.

  2. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

    International Nuclear Information System (INIS)

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L.; West, Daniel C.

    2003-01-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  3. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L. [University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States); West, Daniel C. [Department of Pediatrics, University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States)

    2003-02-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  4. Collagen XVIII Mutation in Knobloch Syndrome with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mahajan, Vinit B.; Olney, Ann Haskins; Garrett, Penny; Chary, Ajit; Dragan, Ecaterina; Lerner, Gary; Murray, Jeffrey; Bassuk, Alexander G.

    2010-01-01

    Knobloch syndrome (KNO) is caused by mutations in the collagen XIII gene (COL18A1) and patients develop encephalocele and vitreoretinal degeneration. Here we report an El Salvadorian family where two sisters showed features of KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA sequencing of COL18A1revealed a homozygous, 2-base pair deletion (c3514-3515delCT) in exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic cleavage product endostatin. KNO patients with mutations in COL18A1 may be at risk for endostatin-related conditions including malignancy. PMID:20799329

  5. NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017.

    Science.gov (United States)

    Brown, Patrick A; Shah, Bijal; Fathi, Amir; Wieduwilt, Matthew; Advani, Anjali; Aoun, Patricia; Barta, Stefan K; Boyer, Michael W; Bryan, Teresa; Burke, Patrick W; Cassaday, Ryan; Coccia, Peter F; Coutre, Steven E; Damon, Lloyd E; DeAngelo, Daniel J; Frankfurt, Olga; Greer, John P; Kantarjian, Hagop M; Klisovic, Rebecca B; Kupfer, Gary; Litzow, Mark; Liu, Arthur; Mattison, Ryan; Park, Jae; Rubnitz, Jeffrey; Saad, Ayman; Uy, Geoffrey L; Wang, Eunice S; Gregory, Kristina M; Ogba, Ndiya

    2017-09-01

    The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management. Copyright © 2017 by the National Comprehensive Cancer Network.

  6. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  7. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2018-01-01

    . PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483......BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival...... to improve survival in relapsed childhood ALL....

  8. Technical relapsed testicular irradiation for acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-01-01

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  9. Genital Infection as a First Sign of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Naoki Oiso

    2010-02-01

    Full Text Available Fournier’s gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier’s gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy.

  10. Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia

    OpenAIRE

    Hou, Qianqian; Liao, Fei; Zhang, Shouyue; Zhang, Duyu; Zhang, Yan; Zhou, Xueyan; Xia, Xuyang; Ye, Yuanxin; Yang, Hanshuo; Li, Zhaozhi; Wang, Leiming; Wang, Xi; Ma, Zhigui; Zhu, Yiping; Ouyang, Liang

    2017-01-01

    GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene...

  11. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  12. Differentiation between tuberculosis and leukemia in abdominal and pelvic lymph nodes: evaluation with contrast-enhanced multidetector computed tomography

    Directory of Open Access Journals (Sweden)

    Ge Zhang

    2015-03-01

    Full Text Available PURPOSE: To compare the characteristics of tubercular vs. leukemic involvement of abdominopelvic lymph nodes using multidetector computed tomography (CT. MATERIALS AND METHODS: We retrospectively reviewed multidetector computed tomography features including lymph node size, shape, enhancement patterns, and anatomical distribution, in 106 consecutive patients with newly diagnosed, untreated tuberculosis (55 patients; 52% or leukemia (51 patients; 48%. In patients with leukemia, 32 (62.7% had chronic lymphocytic leukemia, and 19 (37.3% had acute leukemias; of these, 10 (19.6% had acute myeloid leukemia, and 9 (17.6% had acute lymphocytic leukemia. RESULTS: The lower para-aortic (30.9% for tuberculosis, 63.2% for acute leukemias and 87.5% for chronic lymphocytic leukemia and inguinal (9.1% for tuberculosis, 57.9% for acute leukemias and 53.1% for chronic lymphocytic leukemia lymph nodes were involved more frequently in the three types of leukemia than in tuberculosis (both with p <0.017. Tuberculosis showed peripheral enhancement, frequently with a multilocular appearance, in 43 (78.2% patients, whereas patients with leukemia (78.9% for acute myeloid leukemia and acute lymphocytic leukemia, 87.5% for chronic lymphocytic leukemia demonstrated predominantly homogeneous enhancement (both with p <0.017. For the diagnosis of tuberculosis, the analysis showed that a peripheral enhancement pattern had a sensitivity of 78.2%, a specificity of 100%, and an accuracy of 88.7%. For the diagnosis of leukemia, the analysis showed that a homogeneous enhancement pattern was associated with a sensitivity of 84.3%, a specificity of 94.5%, and an accuracy of 89.6%. CONCLUSION: Our findings indicate that the anatomical distribution and enhancement patterns of lymphadenopathy seen on multidetector computed tomography are useful for differentiating between untreated tuberculosis and leukemia of the abdominopelvic lymph nodes.

  13. Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors

    Science.gov (United States)

    Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

    2012-01-01

    Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

  14. Acute interstitial nephritis in T-cell leukemia in a pediatric patient.

    Science.gov (United States)

    Biro, Erika; Szikszay, Edit; Pethő-Orosz, Petronella; Bigida, László; Balla, György; Szabó, Tamás

    2016-09-01

    Acute lymphoid leukemia is the most frequently occurring malignancy in childhood, but acute tubulointerstitial nephritis with associated acute renal failure as the leading manifestation of leukemia is extremely rare. Only a few pediatric cases have been described in the literature. We present a surprising case in which physical examination and initial investigation were not typical for leukemia. Ultrasound showed only modest kidney enlargement while laboratory results indicated acute renal failure. Renal biopsy indicated tubulointerstitial nephritis, and subsequent steroid treatment led to sudden clinical improvement. One month later, however, the patient returned with typical clinical features of leukemia. Re-evaluation of the original kidney biopsy block indicated T-cell acute lymphoid leukemia. The present case highlights the importance of renal biopsy. © 2016 Japan Pediatric Society.

  15. A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia.

    Science.gov (United States)

    Hale, Victoria; Hale, Gregory A; Brown, Patrick A; Amankwah, Ernest K

    2017-01-01

    Acute leukemia is the most common childhood cancer diagnosis and leading cause of cancer-related death among children and adolescents. Despite substantial improvements in the survival rate of childhood acute leukemia, approximately 20-40% of the patients who undergo treatment develop relapse, with a dismal one third of these patients surviving in the long term. Epigenetics plays an important role in the progression of cancer, and existing evidence suggests a role in childhood acute leukemia relapse. A better understanding of the epigenetic mechanisms in recurrent acute leukemia could potentially lead to novel therapeutic regimens to prevent or treat disease recurrences. In this review, we summarize existing evidence on two of the most studied epigenetic mechanisms, DNA methylation and microRNA expression, in recurrent pediatric acute leukemia. © 2016 S. Karger AG, Basel.

  16. Bovine lymphocytic leukemia: studies of etiology, pathogenesis, and mode of transmission. Progress report No. 19, June 1978-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, D.K.

    1979-07-01

    Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). The presence of BLV particles in lymphocyte cultures from leukemic cattle and cattle with a persistent lymphocytosis has been consistentily demonstrated. Concentrated, cell free, BLV preparations were used to inoculate 12 late stage bovine fetuses (in utero) and two newborn calves. Current studies involve extensive monitoring of these inoculated animals to detect precancerous changes and obtain a detailed description of the events preceding the development of lymphosarcoma. Ongoing monitoring studies will provide a complete record of all changes in the various leukemia associated parameters. We will then be able to detail when, in what sequence, and to what extent each parameter changes in the course of lymphosarcoma development. Fourteen animals were successfully inoculated during the study. Eleven remain alive, and comprise the current monitoring program. All eleven of these animals are definitely infected with BLV, and in nine the infection has substantially progressed with respect to the parameters being monitored. In addition to transmission and monitoring studies, various lymphocyte subpopulations were examined to determine which cell type(s) are involved in the pathogenesis of bovine lymphosarcoma. These studies have conclusively established that B-lymphocytes are the target cells for BLV infection and that they carry the morphologic nuclear abnormality associated with this disease.

  17. [Myeloid/natural killer cell precursor and myeloid/natural killer cell acute leukemia].

    Science.gov (United States)

    Ni, Ming; Chen, Bao-An

    2014-04-01

    With the popularity of flow cytometry, the classification of leukemia become more detailed. Myeloid/natural killer cell precursor acute leukemia and myeloid/natural killer cell acute leukemias are generally recognized as two kinds of rare leukemias and have poor prognosis. The cells expressed both myeloid and lymphatic antigens in these two leukemia and can not be diagnosed by morphology. The only basis to make a definite diagnosis is their unique Immunophenotyping. The role of CD7 and CD56 in these two leukemia are compelling, in the other hand, as the progress of cell differentiation research, there are many new awareness of NK cell differentiation. In this article, the biological origin, clinical manifestation, diagnosis, treatment and the role of CD7 and CD56 in these two leukemia are briefly summarized.

  18. HOXA9 and MEIS1 gene overexpression in the diagnosis of childhood acute leukemias: Significant correlation with relapse and overall survival.

    Science.gov (United States)

    Adamaki, Maria; Lambrou, George I; Athanasiadou, Anastasia; Vlahopoulos, Spiros; Papavassiliou, Athanasios G; Moschovi, Maria

    2015-08-01

    Homeobox genes HOXA9 and MEIS1 are evolutionarily conserved transcription factors with essential roles in both hematopoiesis and leukemogenesis. They act as dominant cooperating oncoproteins that cause acute leukemias bearing MLL translocations and to a lesser extent T-cell acute lymphocytic leukemia (ALL) characterized by other gene fusions. Overexpression is associated with an adverse prognosis in adults. In childhood, the genes have only been investigated in leukemias bearing MLL translocations. The aim of this study was to determine whether overexpression extends to leukemic subtypes other than the MLL-positive subtype in childhood. We use quantitative real-time PCR methodology to investigate gene expression in 100 children with acute leukemias and compare them to those of healthy controls. We show that abnormally high HOXA9 and MEIS1 gene expression is associated with a variety of leukemic subtypes, including various maturation stages of B-cell ALL and cytogenetic types other than the MLL-positive population, thus suggesting that the genes are implicated in the development of a broad range of leukemic subtypes in childhood. In addition, we show that HOXA9 and MEIS1 overexpression are inversely correlated with relapse and overall survival, so the genes could become useful predictive markers of the clinical course of pediatric acute leukemias. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Elucidation and modulation of glucocorticoid-induced apoptosis in acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Eberhart, K.

    2011-01-01

    This thesis deals with the elucidation of the synergistic effect of the glucocorticoid dexamethasone and the metabolic modulator 2-deoxyglucose on apoptosis induction in two in vitro model systems of childhood acute lymphoblastic leukemia. 2-deoxyglucose accelerated the kinetics of, and increased the sensitivity to, glucocorticoid-induced apoptosis in two leukemia cell lines. In primary lymphocytes from healthy donors, in contrast, 2-deoxyglucose and dexamethasone did not act synergistically on apoptosis induction. To elucidate the molecular basis of the synergistic effect, glycolysis by means of glucose uptake, lactate production, ATP levels, glucose transporter and hexokinase expression and mitochondrial oxygen consumption was analyzed in treated vs. untreated cells. The study revealed a downregulation of gene expression of the glucose transporter GLUT1 and hexokinase 2 (HK2), release of HK2 from the outer mitochondrial membrane, as well as reduced glycolysis and mitochondrial respiration. Moreover, the analysis of the mitochondrial proteome by 2 dimensional differential gel electrophoresis after treatment with 2-deoxyglucose and dexamethasone revealed the regulation of several interesting candidate proteins involved in treatment related apoptosis. (author)

  20. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  1. Detection of trisomy 12 by fluorescent in situ hybridization (FISH in chronic lymphocytic leukemia

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    Maria de Lourdes L.F. Chauffaille

    2000-09-01

    Full Text Available Chronic lymphocytic leukemia (CLL presents a varying incidence of karyotypic abnormalities whose detection is complicated by difficulties in obtaining mitosis for analysis in this type of mature lymphocyte disorder. Since the introduction of molecular cytogenetics (FISH = fluorescent in situ hybridization, applying centromeric probes for chromosome 12 has made it possible to detect a higher percentage of trisomy 12 cases. The objective of the present study was to detect trisomy 12 by FISH (alpha satellite probe in 13 patients with CLL whose karyotypes by G-banding were either normal or inadequate. Using this method trisomy 12 was detected in three patients in a percentage of positive cells varying from 55.5% to 79%, showing that FISH is a sensitive and highly specific method for trisomy detection and should be routinely performed when the karyotype is normal.A leucemia linfocítica crônica (CLL apresenta incidência variável de anomalias de cariótipo devido às dificuldades em se obter mitose para análise. Desde a introdução da citogenética molecular (FISH = hibridação in situ por fluorescência usando sonda centromérica para o cromossomo 12 foi possível detectar uma maior porcentagem de casos com trissomia 12. O objetivo deste trabalho foi de detectar trissomia 12 por FISH (sonda alfa satélite em 13 pacientes com CLL cujos cariótipos por banda G haviam sido normais ou sem resultado. Três pacientes apresentaram trissomia 12 por este método com uma porcentagem de células trissômicas variando de 55,5 a 79%, demonstrando que a FISH é um método sensível e altamente específico para detecção de trissomia 12.

  2. Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Rodriguez-Rodriguez, Sergio; Pomerantz, Alan; Demichelis-Gomez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benitez, Olga; Aguayo-Gonzalez, Alvaro

    2016-01-01

    The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

  3. [The expression and clinical significance of miR-203 in pediatric acute leukemia].

    Science.gov (United States)

    Wang, Na; Pan, Jian; Cao, Lan; Lu, Jun; Xiao, Pei-fang; Zhao, Wen-li; Hu, Shao-yan; Chai, Yi-huan

    2013-09-01

    To investigate the methylation, expression and clinical significance of miR-203 in pediatric acute leukemia. The methylation status of miR-203 promoter CpG islands was detected with methylation-specific polymerase chain reaction. The expression of miR-203 was detected by Taqman real- time quantitative polymerase chain reaction. And the clinical significance of miR-203 in pediatric acute leukemia (ALL) was also analyzed. The promoter of miR-203 was unmethylated in all of 31 pediatric acute lymphoblastic leukemia, all of 15 pediatric acute myeloid leukemia (AML) and all of 23 controls. The relative expression levels of miR-203 in controls, pediatric acute leukemia, ALL and AML were 16.93±6.31, 48.97±10.38, 55.88±12.91, 24.28±9.10 respectively. The results indicated that miR-203 was significantly up- regulated in pediatric acute leukemia (P=0.011) and ALL (P=0.009), not in pediatric AML (P=0.514) compared with control. The expression of miR-203 was significantly related with the gender, immunophenotype, chromosome, fusion gene, BCR-ABL, SIL-TAL1 and prednisone experiment in pediatric ALL and the gender, chromosome, fusion gene, SIL-TAL1 in pediatric acute leukemia (Ppediatric acute leukemia. miR- 203 may be a protooncogene involved in the formation of pediatric acute leukemia and ALL. Further analyses indicated that high expression of miR-203 may be associated with poor prognosis of pediatric ALL and acute leukemia.

  4. Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia

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    Fredrick Hogan

    2014-01-01

    Full Text Available Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT. A 55-year-old man with chronic lymphocytic leukemia (CLL received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.

  5. Cytotoxic effect of Spirulina platensis extracts on human acute leukemia Kasumi-1 and chronic myelogenous leukemia K-562 cell lines

    OpenAIRE

    Flores Hernandez, Flor Yohana; Khandual, Sanghamitra; Ramírez López, Inocencia Guadalupe

    2017-01-01

    Objective: To evaluate the cytotoxic effects of Spirulina platensis extracts on acute leukemia Kasumi-1 and chronic leukemia K-562 cancer cell lines. Methods: Various concentrations of Spirulina platensis extracts (0.25–50.00 mg/mL) obtained with different solvents were used to treat cell lines for 72 h. For cytotoxic effect studies, cell viability test with trypan blue solution, MTT assay and microscopic cytomorphological assessment were done. Results: Spirulina extract obtained with 7...

  6. ACUTE MYELOGENOUS LEUKEMIA PRESENTING WITH ABRUPT ONSET LEUKEMIA CUTIS IN A YOUNG BOY: A RARE CASE REPORT

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    Lohit Kumar

    2015-05-01

    Full Text Available We report an 25 - year - old young male patient who presented with sudden onset multiple generalized skin lesions of dusky erythematous plaques of various size and shape all over the body which tends to bleed on rubbing. Histological evaluation revealed leukemia cutis wit h underlying atypical infiltrate contained atypical myeloid forms consistent with acute myelogenous leukemia (AML. His skin biopsy provided the first evidence of progression to AML. AML presenting with sudden onset leukemia cutis in a young boy is an extr emely rare entity

  7. Epigenomics of leukemia: from mechanisms to therapeutic applications.

    Science.gov (United States)

    Florean, Cristina; Schnekenburger, Michael; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc

    2011-10-01

    Leukemogenesis is a multistep process in which successive transformational events enhance the ability of a clonal population arising from hematopoietic progenitor cells to proliferate, differentiate and survive. Clinically and pathologically, leukemia is subdivided into four main categories: chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphocytic leukemia and acute myeloid leukemia. Leukemia has been previously considered only as a genetic disease. However, in recent years, significant advances have been made in the elucidation of the leukemogenesis-associated processes. Thus, we have come to understand that epigenetic alterations including DNA methylation, histone modifications and miRNA are involved in the permanent changes of gene expression controlling the leukemia phenotype. In this article, we will focus on the epigenetic defects associated with leukemia and their implications as biomarkers for diagnostic, prognostic and therapeutic applications.

  8. Multiplex fusion gene testing in pediatric acute myeloid leukemia.

    Science.gov (United States)

    Iijima-Yamashita, Yuka; Matsuo, Hidemasa; Yamada, Miho; Deguchi, Takao; Kiyokawa, Nobutaka; Shimada, Akira; Tawa, Akio; Takahashi, Hiroyuki; Tomizawa, Daisuke; Taga, Takashi; Kinoshita, Akitoshi; Adachi, Souichi; Horibe, Keizo

    2018-01-01

    Gene abnormalities, particularly chromosome rearrangements generating gene fusion, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification, but the results are not always consistent with those of reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and from acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation. Multiplex quantitative RT-PCR was performed to detect eight important fusion genes: AML1(RUNX1)-ETO(RUNX1T1), CBFB-MYH11, MLL(KMT2A)-AF9(MLLT3), MLL-ELL, MLL-AF6(MLLT4), FUS(TLS)-ERG, NUP98-HOXA9, and PML-RARA. Fusion genes were detected in 207 (46.2%) of the 448 AML-05 patient samples. After exclusion of two samples with PML-RARA, no chromosomal abnormalities were identified on karyotyping in 19 of 205 patients (9.3%) positive for fusion genes on RT-PCR. Fusion genes were confirmed on fluorescence in situ hybridization (FISH) in 11 of these 19 patients. In contrast, fusion genes were detected in 37 of 39 patients (94.9%) from the AML-P05 study, and 33 of these results were consistent with the karyotyping. There were discrepancies in four patients (10.8%), three with normal karyotypes and one in whom karyotyping was not possible. All four of these patients were PML-RARA positive on FISH. Multiplex quantitative RT-PCR-based fusion gene screening may be effective for diagnosis of pediatric AML. © 2017 Japan Pediatric Society.

  9. Novel Biomarker Proteins in Chronic Lymphocytic Leukemia: Impact on Diagnosis, Prognosis and Treatment.

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    Lee Admoni-Elisha

    Full Text Available In many cancers, cells undergo re-programming of metabolism, cell survival and anti-apoptotic defense strategies, with the proteins mediating this reprogramming representing potential biomarkers. Here, we searched for novel biomarker proteins in chronic lymphocytic leukemia (CLL that can impact diagnosis, treatment and prognosis by comparing the protein expression profiles of peripheral blood mononuclear cells from CLL patients and healthy donors using specific antibodies, mass spectrometry and binary logistic regression analyses and other bioinformatics tools. Mass spectrometry (LC-HR-MS/MS analysis identified 1,360 proteins whose expression levels were modified in CLL-derived lymphocytes. Some of these proteins were previously connected to different cancer types, including CLL, while four other highly expressed proteins were not previously reported to be associated with cancer, and here, for the first time, DDX46 and AK3 are linked to CLL. Down-regulation expression of two of these proteins resulted in cell growth inhibition. High DDX46 expression levels were associated with shorter survival of CLL patients and thus can serve as a prognosis marker. The proteins with modified expression include proteins involved in RNA splicing and translation and particularly mitochondrial proteins involved in apoptosis and metabolism. Thus, we focused on several metabolism- and apoptosis-modulating proteins, particularly on the voltage-dependent anion channel 1 (VDAC1, regulating both metabolism and apoptosis. Expression levels of Bcl-2, VDAC1, MAVS, AIF and SMAC/Diablo were markedly increased in CLL-derived lymphocytes. VDAC1 levels were highly correlated with the amount of CLL-cancerous CD19+/CD5+ cells and with the levels of all other apoptosis-modulating proteins tested. Binary logistic regression analysis demonstrated the ability to predict probability of disease with over 90% accuracy. Finally, based on the changes in the levels of several proteins in

  10. [Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

    Science.gov (United States)

    Schlenk, R F; Döhner, K; Döhner, H

    2013-02-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

  11. Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

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    Yunbao Pan

    2017-06-01

    Full Text Available Acute myeloid leukemia (AML is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

  12. First-line treatment of acute lymphoblastic leukemia with pegasparaginase

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    Riccardo Masetti

    2009-07-01

    Full Text Available Riccardo Masetti, Andrea PessionPediatric Oncology and Hematology Unit “Lalla Seràgnoli”, University of Bologna, Bologna, ItalyAbstract: Acute lymphoblastic leukemia (ALL accounts for almost 4000 cases annually in the United States, approximately two thirds of which are in children and adolescents. Treatment results of ALL have improved considerably in the past decade, due to an optimal stratification of patients and a rational use of different antileukemic agents among which L-asparaginase (L-ASNase plays a fundamental role. This drug has been used in pediatric ALL chemotherapy protocols for almost 3 decades. In the 1970s and 1980s a chemically modified form of this enzyme called pegasparaginase (PEG-ASNase was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. The different advantages of PEG-ASNase have been demonstrated in many clinical studies, the last of which underline the utility of this drug in front-line therapy of ALL. In this review, we discuss the pharmacological advantages and clinical potential of PEG-ASNase and its important use in first-line treatment of ALL.Keywords: pegasparaginase, acute, lymphoblastic leukemia, pegylation

  13. Evolving Therapies in Acute Myeloid Leukemia: Progress at Last?

    Science.gov (United States)

    DeAngelo, Daniel J; Stein, Eytan M; Ravandi, Farhad

    2016-01-01

    Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials. The revolution in understanding the genetics of AML, facilitated by next-generation sequencing, has led to many new drugs against driver mutations. Better methods of identification of leukemic blasts have provided us with better means to detect the disease left behind after cytotoxic chemotherapy regimens. This measurable residual disease has been correlated with poorer relapse-free survival, demonstrating the need for novel strategies to eradicate it to improve the outcome of patients with acute leukemias. In this article, we discuss adapting and improving AML therapy by age and comorbidities, emerging targeted therapies in AML, and minimal residual disease (MRD) assessment in AML.

  14. Acute Myeloid Leukemia: Clinical Spectrum of 125 Patients.

    Science.gov (United States)

    Sultan, Sadia; Zaheer, Hasan Abbas; Irfan, Syed Mohammed; Ashar, Sana

    2016-01-01

    Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1).

  15. Ibrutinib treatment of a patient with relapsing chronic lymphocytic leukemia and sustained remission of Richter syndrome.

    Science.gov (United States)

    Albi, Elisa; Baldoni, Stefano; Aureli, Patrizia; Dorillo, Erica; Del Papa, Beatrice; Ascani, Stefano; Di Ianni, Mauro; Falzetti, Franca; Sportoletti, Paolo

    2017-11-15

    Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS. The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation. He was treated with FCR with partial response. In 2013, he progressed to RS, not clonally related to the underlying CLL. The patient was treated with anthracycline- and platinum-based regimens, obtaining a complete remission. After 3 years, he presented a CLL progression with worsening lymphocytosis, anemia, thrombocytopenia, increased splenomegaly, and lymphadenopathies. Positron emission tomography-computed tomography scan excluded pathologic uptake. Thus, he was started on ibrutinib. At 12 months' follow-up, we observed white blood cell normalization, increased hemoglobin and platelet levels, disappearance of lymphadenopathy, and spleen size reduction. Therapy was well-tolerated with no evidence of RS. This case demonstrates sustained RS remission in a patient with CLL under ibrutinib therapy, thus improving our knowledge on the use of this new drug in CLL and beyond.

  16. NOTCH and NF-κB interplay in chronic lymphocytic leukemia is independent of genetic lesion.

    Science.gov (United States)

    Baldoni, Stefano; Sportoletti, Paolo; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; Rosati, Emanuela; Ciurnelli, Raffaella; Marconi, Pierfrancesco; Falzetti, Franca; Di Ianni, Mauro

    2013-08-01

    The NOTCH and nuclear factor kappa B (NF-κB) pathways are both constitutively activated in Chronic Lymphocytic Leukemia (CLL). We first described the NOTCH1 PEST domain mutation in a CLL subgroup, but the activation of the NOTCH pathway in NOTCH1-unmutated cases remains unexplained. Here, we investigated whether genetic lesions in the NF-κB/NOTCH loop might support the NOTCH activation status by sequencing negative (TNFAIP3/A20) and positive (TRAF2, TRAF5, TNFRSF11A/RANK, MAP3K7/TAK1, and CARD11) regulators of NF-κB together with NF-κB targets on the NOTCH pathway, the NOTCH ligands Jagged1 and Jagged2, in CLL patients. The sequence analysis revealed four missense mutations for A20, TRAF2, TRAF5 and RANK1 genes, all causing a change in amino acid group from polar to non-polar, but functional domains were not involved. Specific predictive software analyses confirmed that the amino acid changes have a low-functional impact on the protein. Our results show that in CLL, NF-κB regulators and Jagged are both unmutated, suggesting that the Jagged-mediated interplay between NF-κB and NOTCH is independent of genetic lesions.

  17. A systematic approach for peptide characterization of B-cell receptor in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Díez, Paula; Ibarrola, Nieves; Dégano, Rosa M; Lécrevisse, Quentin; Rodriguez-Caballero, Arancha; Criado, Ignacio; Nieto, Wendy G; Góngora, Rafael; González, Marcos; Almeida, Julia; Orfao, Alberto; Fuentes, Manuel

    2017-06-27

    A wide variety of immunoglobulins (Ig) is produced by the immune system thanks to different mechanisms (V(D)J recombination, somatic hypermutation, and antigen selection). The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance to developing targeted vaccines or treatments for specific diseases or infections. Thus, genomics and proteomics techniques (such as Next-Generation Sequencing (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig sequencing and serum Ig peptide profiling in a high-throughput manner. However, the peptide characterization of membrane-bound Ig (e.g., B-cell receptors, BCR) is still a challenge mainly due to the poor recovery of mentioned Ig.Herein, we have evaluated three different sample processing methods for peptide sequencing of BCR belonging to chronic lymphocytic leukemia (CLL) B cells identifying up to 426 different peptide sequences (MS/MS data are available via ProteomeXchange with identifier PXD004466). Moreover, as a consequence of the results here obtained, recommended guidelines have been described for BCR-sequencing of B-CLL samples by MS approaches.For this purpose, an in-house algorithm has been designed and developed to compare the MS/MS results with those obtained by molecular biology in order to integrate both proteomics and genomics results and establish the steps to follow when sequencing membrane-bound Ig by MS/MS.

  18. Preferential use of unmutated immunoglobulin heavy variable region genes in Boxer dogs with chronic lymphocytic leukemia.

    Science.gov (United States)

    Rout, Emily D; Burnett, Robert C; Labadie, Julia D; Yoshimoto, Janna A; Avery, Anne C

    2018-01-01

    Human chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, and immunoglobulin heavy variable region (IGHV) gene mutational status is an important prognostic marker. IGHV mutational status has not been previously examined in canine CLL. We sequenced the IGHV-D-J rearrangements from 55 canine patients with CLL, including 36 non-Boxer and 19 Boxer dogs. The majority of non-Boxers (75%) had mutated IGHV genes, whereas the majority of Boxers (79%) had unmutated IGHV genes. IGHV3-41 and IGHV3-67 gene usage was significantly higher in Boxers with CLL compared to non-Boxers. Additionally, 11 Boxers with large B-cell lymphoma and the normal IGHV repertoire of six control dogs (three Boxers and three non-Boxers) were sequenced. IGHV3-41 was preferentially used in Boxers with other forms of lymphoma and without lymphoproliferative disease. However, preferential use of unmutated IGHV genes was unique to Boxers with CLL, suggesting Boxers may be a valuable model to investigate unmutated CLL.

  19. IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Dong, Shuai; Guinn, Daphne; Dubovsky, Jason A; Zhong, Yiming; Lehman, Amy; Kutok, Jeffery; Woyach, Jennifer A; Byrd, John C; Johnson, Amy J

    2014-12-04

    Chronic lymphocytic leukemia (CLL) displays constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of B-cell receptor (BCR) signaling. Previous studies have shown that an oral PI3K p110δ inhibitor idelalisib exhibits promising activity in CLL. Here, we demonstrate that a dual PI3K p110δ and p110γ inhibitor, IPI-145, antagonizes BCR crosslinking activated prosurvival signals in primary CLL cells. IPI-145 causes direct killing in primary CLL cells in a dose- and time-dependent fashion, but does not generate direct cytotoxicity to normal B cells. However, IPI-145 does reduce the viability of normal T and natural killer cells and decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Furthermore, IPI-145 overcomes the ibrutinib resistance resulting from treatment-induced BTK C481S mutation. Collectively, these studies provide rationale for ongoing clinical evaluation of IPI-145 as a targeted therapy for CLL and related B-cell lymphoproliferative disorders. © 2014 by The American Society of Hematology.

  20. Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation

    Directory of Open Access Journals (Sweden)

    Kaijun Huang

    2016-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL-induced immunodeficiency has been implicated in the occurrence of several secondary or concurrent malignancies. We hereby present the first case of combined CLL and pancreatic neuroendocrine tumor as collision neoplasms within metastatic periportal lymphadenopathy in a 62-year-old patient who presented with obstructive jaundice. An ovoid nodular mass was seen posterior to the head of the pancreas on magnetic resonance cholangiopancreatography and the patient subsequently underwent endoscopic retrograde cholangiopancreatography, with successful placement of two stents within the identified hilar stricture. Tn-111 pentetreotide scintigraphy with single-photon emission computed tomography (CT/CT disclosed two foci of somatostatin receptor positive tissue in the upper abdomen correlating to the previously seen porta hepatis and portacaval lymphadenopathy and the patient was treated with octreotide. Simultaneous onset of CLL and secondary malignancies that each has a different disease status is a rare phenomenon but is important to diagnose for establishing an appropriate treatment strategy, which in certain cases may involve the use of agents active in both types of malignancy to minimize toxicity.

  1. Prognostic signature and clonality pattern of recurrently mutated genes in inactive chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Hurtado, A M; Chen-Liang, T-H; Przychodzen, B; Hamedi, C; Muñoz-Ballester, J; Dienes, B; García-Malo, M D; Antón, A I; Arriba, F de; Teruel-Montoya, R; Ortuño, F J; Vicente, V; Maciejewski, J P; Jerez, A

    2015-01-01

    An increasing numbers of patients are being diagnosed with asymptomatic early-stage chronic lymphocytic leukemia (CLL), with no treatment indication at baseline. We applied a high-throughput deep-targeted analysis, especially designed for covering widely TP53 and ATM genes, in 180 patients with inactive disease at diagnosis, to test the independent prognostic value of CLL somatic recurrent mutations. We found that 40/180 patients harbored at least one acquired variant with ATM (n=17, 9.4%), NOTCH1 (n=14, 7.7%), TP53 (n=14, 7.7%) and SF3B1 (n=10, 5.5%) as most prevalent mutated genes. Harboring one ‘sub-Sanger' TP53 mutation granted an independent 3.5-fold increase of probability of needing treatment. Those patients with a double-hit ATM lesion (mutation+11q deletion) had the shorter median time to first treatment (17 months). We found that a genomic variable: TP53 mutations, most of them under the sensitivity of conventional techniques; a cell phenotypic factor: CD38-positive expression; and a classical marker as β2-microglobulin, remained as the unique independent predictors of outcome. The high-throughput determination of TP53 status, particularly in this set of patients frequently lacking high-risk chromosomal aberrations, emerges as a key step, not only for prediction modeling, but also for exploring mutation-specific therapeutic approaches and minimal residual disease monitoring

  2. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

    Science.gov (United States)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-03-09

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

  3. Clinical Practice Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL) in The Netherlands.

    Science.gov (United States)

    Kersting, Sabina; Neppelenbroek, Suzanne I M; Visser, Hein P J; van Gelder, Michel; Levin, Mark-David; Mous, Rogier; Posthuma, Ward; van der Straaten, Hanneke M; Kater, Arnon P

    2018-01-01

    In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline. This was evidence-based whenever possible, but in cases of low evidence, an expert-based recommendation was formulated with input of the entire working party. The draft guideline was sent to all hematologists in the Netherlands for comment and was subsequently approved. Recommendations were formulated on diagnostic tests and work-up before treatment. Also, recommendations were made for treatment with fludarabine-cyclophosphamide-rituximab, bendamustine-rituximab, chlorambucil with anti-CD20 antibody, ibrutinib, idelalisib-rituximab, venetoclax, and allogeneic stem cell transplantation. In the revised Dutch CLL guidelines, chemo-immunotherapy is still the cornerstone of CLL treatment with novel targeted drugs for specific risk groups. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. PROGNOSTIC VALUE OF TUMOR NECROSIS FACTOR-ALPHA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    E. N. Zotina

    2016-01-01

    Full Text Available The prognostic value of tumor necrosis factor-alfa (TNFα, a pro-inflammatory cytokine was studied in 140 patients with a newly diagnosed chronic lymphocytic leukemia (CLL. TNFα contents in blood serum was determined using ELISA method. A significant increase of serum TNFα was shown in patients with newly diagnosed CLL, as compared to healthy individuals. Dependence of the cytokine concentration on clnical stage and course of disease was revealed: the highest levels of serum TNFα were registered in patients with advanced disease and/or CLL progression. Distinct correlations were revealed between the studied cytokine amounts and clinical laboratory parameters reflecting the cell proliferative activity and tumor clone size. Immunochemotherapy was accompanied by a significant reduction of TNFα levels. According to the data from multivariate regression analysis. TNFα level of at the time of the diagnosis was an independent predictor of overall survival. Hence, TNFα plays an important role in CLL pathogenesis and may be used as an additional predictive factor for CLL outcomes.

  5. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

    2011-01-01

    Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo

  6. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

    Science.gov (United States)

    Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

    2011-01-01

    Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo. PMID:22829125

  7. Complex chromosomal aberrations in chronic lymphocytic leukemia are associated with cellular drug and irradiation resistance.

    Science.gov (United States)

    Koski, T; Karhu, R; Visakorpi, T; Vilpo, L; Knuutila, S; Vilpo, J

    2000-07-01

    Drug resistance is a major problem in chemotherapy of chronic lymphocytic leukemia (CLL). The genetic basis and molecular pathogenesis of drug resistance in CLL remain poorly understood. Here, we have investigated the association between chromosomal aberrations and cellular resistance of CLL cells against seven drugs, gamma and ultraviolet irradiation. Samples were obtained from 35 patients having a classical form of B-CLL. Chromosomal aberrations were first analyzed by traditional karyotyping improved by using optimized mitogen combinations. DNA sequence copy number changes throughout the genome were next screened by comparative genomic hybridization. Finally, fluorescence in situ hybridization was used to detect trisomy 12 and loss of Rb and deletions at chromosome 11. The cellular sensitivity in vitro was assessed by the reduction of macromolecular protein synthesis measured as incorporation of radioactive L-leucine as an endpoint. The overall analysis disclosed a statistically highly significant difference in cellular drug resistance between patients having at least three aberrations compared with patients with fewer or no aberrations. This strongly indicates that complex rather than simple molecular mechanisms are responsible for the drug and irradiation resistance in CLL. According to published results, complex aberrations are constantly associated with poor prognosis in CLL. We demonstrated here that complex chromosomal aberrations were associated with cellular irradiation and drug resistance, which, on the other hand, may be responsible for the poor clinical outcome in CLL.

  8. GENOMIC PROFILING BY MULTIPLEX LIGATION - DEPENDENT PROBE AMPLIFICATION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Georgiana-Emilia Grigore

    2013-11-01

    Full Text Available The clinical management of severe pathological conditions, such as B-cell chronic lymphocytic leukemia (B-CLL, is subject to continuous optimization and re-evaluation. Patients may fully benefit from rapid, standardized laboratory tools designed to facilitate their early stratification according to disease risk, stage and prognosis. Such technologies may also aid the clinician in selecting the therapeutic option with the greatest chances of success. The presence of specific genetic abnormalities are frequently associated with the clinical outcome of oncologic patients in general, and B-CLL patients in particular. In the current study, a group of 58 B-CLL patients were evaluated for the detection of gene copy number alterations (deletions or duplication/ amplifications within 45 distinct genetic targets, by means of a novel molecular methodology, Multiplex Ligation - Dependent Probe Amplification (MLPA. Simple or complex genetic defects were identified in 67% of cases, and the most common aberrations observed were: deletion of the short arm of chromosome 13 in 33% of cases, deletion of the long arm of chromosome 11 in 16% of cases, trisomy 12 in 16% of cases, and deletion of the short arm of chromosome 17 in 7% of cases. The main conclusion of the study presented here points towards MLPA as a potential key step of clinical management protocols in B-CLL, providing that it will be fully standardised for routine diagnosis.

  9. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    Science.gov (United States)

    Berndt, Sonja I.; Camp, Nicola J.; Skibola, Christine F.; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S.; Smedby, Karin E.; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S.; Lan, Qing; Teras, Lauren R.; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R.; Hartge, Patricia; Purdue, Mark P.; Birmann, Brenda M.; Vajdic, Claire M.; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G.; Shanafelt, Tait D.; Novak, Anne J.; Kay, Neil E.; Liebow, Mark; Cunningham, Julie M.; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T.; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A.; Diver, W Ryan; Link, Brian K.; Weiner, George J.; Conde, Lucia; Bracci, Paige M.; Riby, Jacques; Arnett, Donna K.; Zhi, Degui; Leach, Justin M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Goldin, Lynn R.; Strom, Sara S.; Leis, Jose F.; Weinberg, J. Brice; Caporaso, Neil E.; Norman, Aaron D.; De Roos, Anneclaire J.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María- Dolores; Vermeulen, Roel C. H.; Travis, Ruth C.; Southey, Melissa C.; Milne, Roger L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R.; Villano, Danylo J.; Maria, Ann; Spinelli, John J.; Gascoyne, Randy D.; Connors, Joseph M.; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M.; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E.; Snowden, John A.; Wright, Josh; Fraumeni, Joseph F.; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Slager, Susan L.

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  10. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Badoux, Xavier C; Keating, Michael J; Wang, Xuemei; O'Brien, Susan M; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop; Wierda, William G

    2011-08-25

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.

  11. Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions.

    Science.gov (United States)

    Jadidi-Niaragh, Farhad; Ghalamfarsa, Ghasem; Yousefi, Mehdi; Tabrizi, Mina Hajifaraj; Shokri, Fazel

    2013-08-01

    Identification of regulatory T cells (Tregs) has led to breaking the dichotomy of the Th1/Th2 axis in the immunopathology of several diseases such as autoimmune diseases and cancer. Despite the presence of extensive information about immunobiology of Tregs in pathogenesis of autoimmune diseases, little is known about the frequency and function of these cells in hematologic malignancies, particularly chronic lymphocytic leukemia (CLL). Recent data have demonstrated increased frequency and intact functional capacity of CD4(+) Tregs in CLL patients. However, the precise role of these cells in the immunopathology of CLL is not well known. While targeting Tregs in cancer diseases seems to be an interesting immunotherapeutic approach, such therapeutic interventions in CLL might be deleterious due to suppression of the tumor-specific adaptive and innate immune responses. Thus, the precise biological and regulatory functions of all Tregs subsets should be carefully investigated before planning any immunotherapeutic interventions based on targeting of Tregs. In this communication, we review the recent data published on immunobiology of Tregs in CLL and discuss about the possibility of targeting Tregs in CLL.

  12. Quantitative and qualitative analysis of regulatory T cells in B cell chronic lymphocytic leukemia.

    Science.gov (United States)

    Mpakou, Vassiliki E; Ioannidou, Heleni-Dikaia; Konsta, Eugene; Vikentiou, Myrofora; Spathis, Aris; Kontsioti, Frieda; Kontos, Christos K; Velentzas, Athanassios D; Papageorgiou, Sotiris; Vasilatou, Diamantina; Gkontopoulos, Konstantinos; Glezou, Irene; Stavroulaki, Georgia; Mpazani, Efthimia; Kokkori, Stella; Kyriakou, Elias; Karakitsos, Petros; Dimitriadis, George; Pappa, Vasiliki

    2017-09-01

    Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4 + CD25 - CD127 - and CD4 + CD25 low CD127 - subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells. These data are further supported by our observations that CLL derived Tregs appear rather incapable of inducing apoptosis of both normal B cells and CLL cells, in contrast to normal Tregs, suggesting an immunoediting effect of CLL cells on Tregs which negatively affects the functionality of the latter and contributes to the failure of Tregs in CLL to efficiently eliminate the abnormal clone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Chronic lymphocytic leukemia: a paradigm of innate immune cross-tolerance.

    Science.gov (United States)

    Jurado-Camino, Teresa; Córdoba, Raúl; Esteban-Burgos, Laura; Hernández-Jiménez, Enrique; Toledano, Victor; Hernandez-Rivas, Jose-Angel; Ruiz-Sainz, Elena; Cobo, Teresa; Siliceo, María; Perez de Diego, Rebeca; Belda, Cristobal; Cubillos-Zapata, Carolina; López-Collazo, Eduardo

    2015-01-15

    Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors. Copyright © 2015 by The American Association of Immunologists, Inc.

  14. Evaluation of chronic lymphocytic leukemia by BAC-based microarray analysis

    Directory of Open Access Journals (Sweden)

    McDaniel Lisa D

    2011-02-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is a highly variable disease with life expectancies ranging from months to decades. Cytogenetic findings play an integral role in defining the prognostic significance and treatment for individual patients. Results We have evaluated 25 clinical cases from a tertiary cancer center that have an established diagnosis of CLL and for which there was prior cytogenetic and/or fluorescence in situ hybridization (FISH data. We performed microarray-based comparative genomic hybridization (aCGH using a bacterial artificial chromosome (BAC-based microarray designed for the detection of known constitutional genetic syndromes. In 15 of the 25 cases, aCGH detected all copy number imbalances identified by prior cytogenetic and/or FISH studies. For the majority of those not detected, the aberrations were present at low levels of mosaicism. Furthermore, for 15 of the 25 cases, additional abnormalities were detected. Four of those cases had deletions that mapped to intervals implicated in inherited predisposition to CLL. For most cases, aCGH was able to detect abnormalities present in as few as 10% of cells. Although changes in ploidy are not easily discernable by aCGH, results for two cases illustrate the detection of additional copy gains and losses present within a mosaic tetraploid cell population. Conclusions Our results illustrate the successful evaluation of CLL using a microarray optimized for the interrogation of inherited disorders and the identification of alterations with possible relevance to CLL susceptibility.

  15. Novel synthetic drugs currently in clinical development for chronic lymphocytic leukemia.

    Science.gov (United States)

    Robak, Pawel; Robak, Tadeusz

    2017-11-01

    Over the last few years, several new synthetic drugs, particularly Bruton's tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K) and BCL-2 inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). Areas covered: This review highlights key aspects of BTK, PI3K and BCL-2 inhibitors that are currently at various stages of preclinical and clinical development in CLL. A literature review of the MEDLINE database for articles in English concerning CLL, B-cell receptor, BCL-2 antagonists, BTK inhibitors and PI3K inhibitors, was conducted via PubMed. Publications from 2000 through July 2017 were scrutinized. The search terms used were acalabrutinib, ACP-196, BGB-3111, ONO-4059, GS-4059, duvelisib, IPI-145, TGR-1202, copanlisib, Bay 80-6946, buparlisib, BKM-120, BCL-2 inhibitors, venetoclax, ABT-263, navitoclax, CDK inhibitors, alvocidib, flavopiridol, dinaciclib, SCH 727,965, palbociclib, PD-0332991, in conjunction with CLL. Conference proceedings from the previous five years of the ASH and EHA Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: The use of new synthetic drugs is a promising strategy for the treatment of CLL. Data from ongoing and future clinical trials will aid in better defining the status of new drugs in the treatment of CLL.

  16. The role of CD44 in the pathophysiology of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Julia Christine Gutjahr

    2015-04-01

    Full Text Available CD44 interactions with hyaluronan (HA play a key role in various malignancies, supporting tumor cell migration, adhesion, and survival. In contrast to solid tumors, the expression of CD44 standard and variant forms and their functional interplay with hyaluronan is less understood in hematological malignancies. Chronic lymphocytic leukemia (CLL is a highly abundant B cell malignancy with a well coordinated balance between cell cycle-arrest and proliferation of tumor subpopulations. The long-term survival and proliferation of CLL cells requires their dynamic interactions with stromal and immune cells in lymphoid organs. Interactions of HA with CD44 and HA-mediated motility receptor (RHAMM contribute to CLL cell localization, and hence CLL pathophysiology, by shaping homing, interstitial migration, and adhesion of the tumor cells. CD44 can complex with key prognostic factors of CLL, particularly CD38 and CD49d, bridging the gap between prognosis and cellular function. Here, we review the current evidence for the individual and associated contributions of CD44 to CLL pathophysiology, the dynamic functional regulation of CD44 upon CLL cell activation, and possible therapeutic strategies targeting CD44 in CLL.

  17. Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

    KAUST Repository

    Marcatili, P.

    2013-05-01

    Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated. Copyright © 2013 by The American Association of Immunologists, Inc.

  18. Telomere length analysis in monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia Binet A

    Directory of Open Access Journals (Sweden)

    F.M. Furtado

    Full Text Available Monoclonal B-cell lymphocytosis (MBL is an asymptomatic clinical entity characterized by the proliferation of monoclonal B cells not meeting the diagnosis criteria for chronic lymphocytic leukemia (CLL. MBL may precede the development of CLL, but the molecular mechanisms responsible for disease progression and evolution are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. Here, we determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy volunteers. Twenty-one CLL patients, 11 subjects with high-count MBL, and 6 with low-count MBL were enrolled. Two hundred and sixty-one healthy volunteers aged 0 to 88 years were studied as controls. After diagnosis confirmation, a flow cytometry CD19+CD5+-based cell sorting was performed for the study groups. Telomere length was determined by qPCR. Telomere length was similar in the 3 study groups but shorter in these groups compared to normal age-matched subjects that had been enrolled in a previous study from our group. These findings suggest that telomere shortening is an early event in CLL leukemogenesis.

  19. Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia

    Directory of Open Access Journals (Sweden)

    Sushma Belurkar

    2013-01-01

    Full Text Available Introduction: The classification of acute leukemias has revolutionized over the years. Immunophenotyping of acute leukemia has gained popularity because of its influence on treatment and prognosis of the disease. The various antigens expressed by the leukemic cells can be assessed by flowcytometry (FCA and can be used in rendering specific treatment and predicting the outcome of the different types of acute leukemia. Aims: The main aim of this study was to compare the morphologic and cytochemical diagnoses with flowcytometric diagnoses in acute leukemia and to analyze the usefulness of FCA over morphology. Results: In this study we analyzed 50 cases of acute leukemia and found concordance rate as high as 86% between morphologic/cytochemical diagnosis and flowcytometric diagnosis. Of these, complete concordance was seen in 58% of the cases and partial concordance was seen in 22% of the cases. Non-concordance was seen in only 4% of our cases. In remaining 16% of our cases FCA helped in sub classifying the acute leukemia where morphology and cytochemistry had failed to do so. CD19 and 20 were found to be consistent B-cell markers and CD3 was a very specific marker for T-cell leukemia. CD13 and 33 were important myeloid markers and were aided by other secondary panel of markers like CD14, CD117 and CD41. Conclusion: FCA not only helps in confirming morphologic diagnosis in acute leukemia but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia. Immunophenotyping is of utmorst importance in classifying acute leukemia as it greatly influences the treatment and the prognosis.

  20. Leukemia among participants in military maneuvers at a nuclear bomb test

    International Nuclear Information System (INIS)

    Caldwell, G.G.; Kelley, D.B.; Heath, C.W.

    1980-01-01

    To test the possibility of a casual relationship between leukemia and exposure to nuclear radiation, the frequency of leukemia in personnel observing the detonation of a nuclear device called ''Smoky'' during August 1957 was determined. Of some 3224 men who witnessed the detonation, nine cases of leukemia were observed. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, one of hairy cell lymphocyctic leukemia, and one of acute lymphocytic luekemia. These findings represent a significant increase over the expected leukemia incidence of 3.5 cases. Mean film-badge gamma radiation dose for the study group was 466.2 mrem

  1. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells*

    Science.gov (United States)

    Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas; Fiser, Karel; Hrusak, Ondrej; Lund-Johansen, Fridtjof

    2016-01-01

    Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients. To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation. In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified

  2. Cardiac tamponade mimicking tuberculous pericarditis as the initial presentation of chronic lymphocytic leukemia in a 58-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Nathan Sandeep

    2010-08-01

    Full Text Available Abstract Introduction Chronic lymphocytic leukemia is an indolent disease that often presents with complaints of lymphadenopathy or is detected as an incidental laboratory finding. It is rarely considered in the differential diagnosis of patients presenting with tamponade or a large, bloody pericardial effusion. In patients without known cancer, a large, bloody pericardial effusion raises the possibility of tuberculosis, particularly in patients from endemic areas. However, the signs, symptoms and laboratory findings of pericarditis related to chronic lymphocytic leukemia can mimic tuberculosis. Case Presentation We report the case of a 58-year-old African American-Nigerian woman with a history of travel to Nigeria and a positive tuberculin skin test who presented with cardiac tamponade. She had a mild fever, lymphocytosis and a bloody pericardial effusion, but cultures and stains were negative for acid-fast bacteria. Assessment of blood by flow cytometry and pericardial biopsy by immunohistochemistry revealed CD5 (+ and CD20 (+ lymphocytes in both tissues, demonstrating this to be an unusual manifestation of early stage chronic lymphocytic leukemia. Conclusion Although most malignancies that involve the pericardium clinically manifest elsewhere before presenting with tamponade, this case illustrates the potential for early stage chronic lymphocytic leukemia to present as a large pericardial effusion with tamponade. Moreover, the presentation mimicked tuberculosis. This case also demonstrates that it is possible to treat chronic lymphocytic leukemia-related pericardial tamponade by removal of the fluid without chemotherapy.

  3. Immunological Subtypes of Acute Lymphoblastic Leukemia- Beyond Morphology: Experience from Kidwai State Cancer Institute, Bengaluru, India.

    Science.gov (United States)

    Rajkumar, Namrata N; Vijay, Raghavendra H

    2017-07-01

    Acute lymphoblastic leukemia (ALL) is disease of lymphoid precursors and is the most common cancer. Diagnosis of ALL is made by evaluating morphology and flowcytometric Immunophenotyping (FCI)and is an important adjunct in diagnosis and determining treatment in ALL, with availability of extensive monoclonal antibodies in the recent years there is tremendous progress in the field of FCI, and is a requirement by World Health Organisation for the classification of acute lymphoblastic Leukemia. Flow cytometric immunophenotyping of the leukemic blasts helps in categorization of acute lymphoblastic leukemia as B-ALL or T-ALL. Though ALL is the most common cancer, there is paucity of study in Indian scenario, and very few reports of immunologically subtyping of ALL is reported. To confirm the clinical/morphological diagnosis and to determine immunological subtype of acute lymphoblastic leukemia as per requirement by World Health Organization for the classification of acute lymphoblastic leukemia. At Kidwai State Cancer institute, Bangalore, we have performed of Immunophenotyping in 1425 untreated cases of acute leukemias during January 2012 - August 2015. Flow cytometry analysis of 1425 cases of acute Leukemias were performed, 918 (64.42%) were acute lymphoblastic Leukemia, 688 were B-ALL (74.94%), majority(480) of B-ALL were in children (69.76%), 230 were T-ALL (25.05 %), B-ALL was the most common subtype of acute leukemias. Acute lymphoblastic leukemia is the most common leukemia in adults and children. Immunophenotping helps in confirming the clinical/morphological diagnosis and in determining the immunological subtype of acute lymphoblastic leukemia, thus has an important role in deciding on the treatment regime. ALL is the disease of lymphoid precursors and is more common cancer in children than adults. B-ALL was the most common subtype of acute leukemias both in adults and in children. T-ALL is less common in pediatric population. Flowcytometric techniques are used

  4. A 78-year-old man with acute myeloid leukemia (AML) and acute renal failure.

    Science.gov (United States)

    Tapper, Elliot B; Luptakova, Katarina; Joyce, Robin M; Tzachanis, Dimitrios

    2014-08-30

    Male, 78. Acute myeloid leukemia (AML). Dyspnea • fatigue. Idarubicin followed by cytarabine. Chemotherapy. Hematology. Unusual clinical course. Renal failure is a common presentation of acute myelomonocytic and monocytic leukemia. It is usually the result of a combined glomerular and tubular dysfunction and is associated with a poor prognosis. No guidelines exist for treatment. We herein describe the case of a 78-year-old Caucasian man who presented with acute myeloid leukemia M5, leukostasis with a white count of 340 000/ml, and acute renal failure with a creatinine of 7.7/dL. The patient was initially treated with leukapheresis and 3 days of idarubicin in the setting of continuous renal replacement therapy that resulted in rapid reversal of his renal failure. He then received 7 days of continuous infusion cytarabine and went into a complete remission. Renal failure may complicate the presentation of AML but can be reversible with treatment. Dose adjustment of the chemotherapy is not needed and the treatment can be greatly facilitated with the use of continuous renal replacement therapy, as indicated in our case report. In addition, we emphasize that organ dysfunction, even in elderly patients, is not necessarily a contraindication to aggressive treatment if it is felt to be disease-related and reversible.

  5. Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review.

    Science.gov (United States)

    Lam, Grace Kee See; Leung, Alex Wing Kwan; Ha, Shau Yin; Luk, Chung Wing; Li, Chak Ho; Ling, Siu Cheung; Chiang, Alan Kwok Shing; Li, Chi Kong

    2016-03-01

    Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

  6. Clinicopathologic, Immunophenotypic, Cytogenetic, and Molecular Features of γδ T-Cell Large Granular Lymphocytic Leukemia: An Analysis of 14 Patients Suggests Biologic Differences With αβ T-Cell Large Granular Lymphocytic Leukemia. [corrected].

    Science.gov (United States)

    Yabe, Mariko; Medeiros, L Jeffrey; Wang, Sa A; Konoplev, Sergej; Ok, Chi Young; Loghavi, Sanam; Lu, Gary; Flores, Lauren; Khoury, Joseph D; Cason, R Craig; Young, Ken H; Miranda, Roberto N

    2015-10-01

    T-cell large granular lymphocytic (T-LGL) leukemia is a rare disorder in which the neoplastic cells usually express the αβ T-cell receptor (TCR). To determine the significance of γδ TCR expression in this leukemia, we compared the clinicopathologic, immunophenotypic, and genetic features of patients with T-LGL leukemia expressing γδ TCR or αβ TCR. We used the World Health Organization classification criteria to confirm the diagnosis. All patients were diagnosed and treated at our institution. We identified 14 patients with γδ T-LGL leukemia, 11 men and three women; six (43%) patients had a history of rheumatoid arthritis, 10 (71%) had neutropenia, four (29%) had thrombocytopenia, and three (21%) had anemia. Eight (67%) of 12 patients had a CD4-/CD8- phenotype, and four (33%) had a CD4-/CD8+ phenotype. The median overall survival was 62 months. Patients with γδ T-LGL leukemia were more likely to have rheumatoid arthritis (P = .04), lower absolute neutrophil count (P = .04), lower platelet count (P = .004), and a higher frequency of the CD4-/CD8- phenotype (P < .0001). However, there was no significant difference in overall survival between the two groups (P = .64). Although patients with γδ and αβ T-LGL leukemia show some different clinical or phenotypic features, overall survival is similar, suggesting that γδ TCR expression does not carry prognostic significance. Copyright© by the American Society for Clinical Pathology.

  7. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  8. Role of FAB classification of acute leukemias in era of immunophenotyping.

    Science.gov (United States)

    Sachdeva, Man Updesh Singh; Ahluwalia, Jasmina; Das, Reena; Varma, Neelam; Garewal, G

    2006-10-01

    French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.

  9. Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization.

    Science.gov (United States)

    Heesch, Sandra; Neumann, Martin; Schwartz, Stefan; Bartram, Isabelle; Schlee, Cornelia; Burmeister, Thomas; Hänel, Matthias; Ganser, Arnold; Heuser, Michael; Wendtner, Clemens-Martin; Berdel, Wolfgang E; Gökbuget, Nicola; Hoelzer, Dieter; Hofmann, Wolf-Karsten; Thiel, Eckhard; Baldus, Claudia D

    2013-06-01

    Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.

  10. Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

    Science.gov (United States)

    Chung, Clement; Ma, Hilary

    2017-09-01

    Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia. Evidence indicates that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up-front induction therapy. Core-binding factor acute myeloid leukemia in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer. © 2017 Pharmacotherapy Publications

  11. CD117 expression on blast cells in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Goryainova N.V.

    2015-09-01

    Full Text Available The aim of the present work was to analyze the frequency of CD117 (c-KIT antigen expression on the blast cells in acute myeloid leukemia (AML, evaluation of the presence of the relationship between the expression of the c-KIT and leukemia according to the FAB classification and definition of co-expression of the antigen CD117, antigens CD33 and CD34. The data of 47 patients with AML were diagnosed. M0 AML variant was established in 3 (6% patients, M1 – in 2 (4%, M2 – in 9 (20%, M4 – in 22 (47% and M5 – in 11 (23%. For immunophenotypic stu¬dies monoclonal antibodies (mAb that detect antigens of anti-CD34, anti-CD33 and anti-CD117 (Becton Dickinson, USA were used. The presence of the antigen CD117 was detected in 39 people, accounting for 83% of all surveyed. Antigen c-KIT was present in 48.117.0% cells on average: in all 3 cases – AML M0, in2 cases of AML M1, in 6 cases – AML M2, 20 of 22 cases – AML M4 and in 8 of 11 AML M5 cases. Average levels of CD117 in investigated leukemia cases statistically differed significantly (p=0.0067. Among 39 CD117- positive patients in 25 (53% co-expression of CD117+/CD34+ was revealed. Expression of CD117+/CD34- was observed in 14 cases (30%, CD117-/CD34+ – in 4 cases (8,5%, CD117-/CD34- – in 4 cases (8.5%. CD34 had of 64% of cells of myeloid origin. A high positive cor¬relation between expression of CD117 and CD34 (r=+0,5169 was determined, being statistically significant (p0,0067.

  12. Isolated Extramedullary Relapse of Acute Leukemia after Allogeneic Stem Cell Transplantation: Different Kinetics and Better Prognosis than Systemic Relapse.

    Science.gov (United States)

    Shem-Tov, Noga; Saraceni, Francesco; Danylesko, Ivetta; Shouval, Roni; Yerushalmi, Ronit; Nagler, Arnon; Shimoni, Avichai

    2017-07-01

    Allogeneic stem cell transplantation (SCT) is curative treatment in patients with acute leukemia and myelodysplastic syndrome. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary relapse (iEMR) after SCT is relatively rare and not well characterized. We performed a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR. The 5-year cumulative incidence of bone marrow relapse (BMR) and iEMR was 41.0% and 5.8%, respectively. iEMR occurred significantly later than BMR at 10 and 4 months, respectively (P BMR but did not protect against iEMR. Most patients with iEMR received systemic treatment combined with local radiation and donor lymphocyte infusions when feasible. The 3-year survival after relapse was 8.5% and 30.1% after BMR and iEMR, respectively (P = .002). Patients with a first iEMR continued to have recurrent EMRs, and only a minority progressed to BMR. Second iEMR was also common after first BMR and associated with longer survival than second BMR. iEMR is more frequent in patients with ALL and prior extramedullary disease. It occurs later than BMR and more commonly in patients with chronic GVHD, suggesting less effective graft-versus-leukemia effect in extramedullary sites. Second iEMR is common after a first iEMR but also after a first BMR. Long-term survival is feasible with aggressive treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  13. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

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    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  14. Textural characteristics of bone marrow blast nucleus images with different variants of acute lymphoblastic leukemia

    Science.gov (United States)

    Nikitaev, V. G.; Pronichev, A. N.; Polyakov, E. V.; Mozhenkova, A. V.; Tupitsin, N. N.; Frenkel, M. A.

    2018-01-01

    The paper describes the method of recognition of T - and B - variants of acute lymphoblastic leukemia in microscopic images of blood cells. The method is based on the use of texture characteristics of images. Experimental recognition accuracy evaluation is obtained from the sample of 38 patients (17 with T-ALL and 21 with B-ALL variants of acute lymphoblastic leukemia). The obtained results show the possibility of applying of the proposed approach to the differential diagnosis of T- and B- variants of acute lymphoblastic leukemia.

  15. Problems of prophylactic CNS radiotherapy in acute children's leukemia

    International Nuclear Information System (INIS)

    Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

    1980-01-01

    The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

  16. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  17. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  18. Coagulation Profile at Diagnosis in Patients with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sehgal, Shivali; Sharma, Sunita; Chandra, Jagdish; Nangia, Anita

    2016-10-01

    To evaluate the coagulation parameters at the time of diagnosis in pediatric acute lymphoblastic leukemia (ALL) patients. A total of 65 newly diagnosed ALL patients upto 18 y of age along with 30 age and sex matched controls were included in the study. Coagulation tests including Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (FBG) assay, D-dimer (D-DI) assay, Coagulation inhibitor levels and tests for fibrinolysis were performed. At baseline, APTT of the patients was significantly prolonged (p 0.033), but PT and fibrinogen were comparable in the two groups. Protein C (PC) and Protein S (PS) were both significantly reduced in the cases, while antithrombin was comparable to control values (p DI levels were significantly high (p < 0.001). The onset of leukemia is associated with hemostatic derangement favouring hypercoagulability. The coagulopathy is due to thrombin activation (as evidenced by raised d-dimer). The decreased fibrinolysis (due to reduced tPA and raised PAI-1) and low levels of PC and PS contribute to the hypercoagulable state at the time of diagnosis.

  19. Karyotype complexity and prognosis in acute myeloid leukemia.

    Science.gov (United States)

    Stölzel, F; Mohr, B; Kramer, M; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; Stuhlmann, R; Einsele, H; Krause, S W; Serve, H; Hänel, M; Herbst, R; Neubauer, A; Sohlbach, K; Mayer, J; Middeke, J M; Platzbecker, U; Schaich, M; Krämer, A; Röllig, C; Schetelig, J; Bornhäuser, M; Ehninger, G

    2016-01-15

    A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.

  20. Recent developments in immunotherapy of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Felix S. Lichtenegger

    2017-07-01

    Full Text Available Abstract The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years. Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1 antibody-drug conjugates, (2 T cell-recruiting antibody constructs, (3 chimeric antigen receptor (CAR T cells, (4 checkpoint inhibitors, and (5 dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results. While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts.