Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias

International Nuclear Information System (INIS)

Philip, P.; Pedersen-Bjergaard, J.

1988-01-01

From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease

Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Science.gov (United States)

2017-07-19

Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

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

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

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Kjeld Schmiegelow

2017-04-01

Full Text Available 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 obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically 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 survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

Poor survival of treatment-related acute nonlymphocytic leukemia

International Nuclear Information System (INIS)

Neugut, A.I.; Nieves, J.; Murray, T.; Tsai, Weiyann; Robinson, E.

1990-01-01

Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients

Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

Science.gov (United States)

Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

2011-06-01

The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

Gingival enlargement as an early diagnostic indicator in therapy-related acute myeloid leukemia: A rare case report and review of literature

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Triveni M Gowda

2013-01-01

Full Text Available Treatment for Hodgkin′s lymphoma (HL has resulted in excellent survival rates but is associated with increased risks of secondary therapy-related acute myeloid leukemia (t-AML. Gingival enlargement associated with bleeding and ulceration is the most common rapidly appearing oral manifestations of leukemic involvement. An 8 months pregnant patient reported with generalized gingival enlargement, with localized cyanotic and necrotic papillary areas. Co-relating the hematological report with the oral lesions and her past medical history of HL, a diagnosis of t-AML secondary to treatment for HL was made by the oncologist. As oral lesions are one of the initial manifestations of acute leukemia, they may serve as a significant diagnostic indicator for the dental surgeons and their important role in diagnosing and treating such cases. Furthermore, this case report highlights the serious complication of t-AML subsequent to HL treatment and the important role that a general and oral health care professional may play in diagnosing and treating such cases.

Cytarabine and daunorubicin or idarubicin in induction therapy of Acute Myeloid Leukemia patients

International Nuclear Information System (INIS)

Eivazi-Ziaei, J.; Kermani, I.A.; Nikanfar, A.; Maljaie, H.; Mahmoudpour, A.; Dolatkhah, R.

2010-01-01

Objectives: Acute myeloid leukemia (AML), the most common form of acute leukemia, is treated by remission induction and post-remission therapy. Remission induction is usually achieved by administration of cytarabine along with an anthracycline such as Daunorubicin (DAU) or Idarubicin (IDA). Our objective was see the benefits if any of IDA over DAU in AML therapy. Methodology: Eighty adult AML patients were enrolled in this study, where 40 received DAU and 40 were treated with IDA. Remission status in each subject was studied and response to therapy was subsequently analyzed using SPSS. Results: Complete remission, partial remission and no responsive status were 15, 19, and 14 respectively for patients on DAU and 14, 18, and 11 for patients on IDA protocol. No significant benefit was detected for IDA compared to DAU in response to therapy. Conclusion: We found no benefit in using IDA over DAU in induction therapy for AML patients treated in northwest of Iran. (author)

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

Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

2017-01-01

Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a blood cancer that often gets worse quickly if it is not treated. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about ALL in this expert-reviewed summary.

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...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

The MLL recombinome of acute leukemias in 2017

NARCIS (Netherlands)

C. Meyer; T. Burmeister; D. Gröger (D.); G. Tsaur; L. Fechina; A. Renneville; R. Sutton; N. Venn; M. Emerenciano (M.); Pombo-De-Oliveira, M.S. (M. S.); Barbieri Blunck, C. (C.); Almeida Lopes, B. (B.); J. Zuna; J. Trka (Jan); Ballerini, P. (P.); Lapillonne, H. (H.); E. de Braekeleer; G. Cazzaniga (Gianni); Corral Abascal, L. (L.); V.H.J. van der Velden (Vincent); E. Delabesse; Park, T.S. (T. S.); S.H. Oh (S.); M.L.M. Silva (M. L M); T. Lund-Aho (T.); V. Juvonen (V.); A.S. Moore (A.); O. Heidenreich; Vormoor, J. (J.); Zerkalenkova, E. (E.); Olshanskaya, Y. (Y.); Bueno, C. (C.); P. Menéndez (Pablo); A. Teigler-Schlegel; U. zur Stadt; Lentes, J. (J.); G. Göhring (Gudrun); Kustanovich, A. (A.); O. Aleinikova (O.); Schäfer, B.W. (B. W.); S. Kubetzko (S.); H.O. Madsen; Gruhn, B. (B.); Duarte, X. (X.); P. Gameiro; E. Lippert (Eric); Bidet, A. (A.); J.-M. Cayuela (Jean-Michel); E. Clappier; C.N. Alonso (Cristina); C.M. Zwaan (Christian Michel); M.M. van den Heuvel-Eibrink (Marry); S. Izraeli (Shai); L. Trakhtenbrot; P. Archer (P.); J. Hancock; A. Möricke; Alten, J. (J.); M. Schrappe (Martin); M. Stanulla (Martin); S. Strehl; A. Attarbaschi (Andishe); M.N. Dworzak (Michael); Haas, O.A. (O. A.); R. Panzer-Grümayer (Renate); L. Sedek (Lukasz); Szczepa, T. (T.); A. Caye (Aurélie); Suarez, L. (L.); H. Cavé (Helene); R. Marschalek (Rolf)

2018-01-01

textabstractChromosomal 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

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.

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...

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)

Late effects of childhood leukemia therapy.

Science.gov (United States)

Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J

2011-09-01

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

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Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

2016-01-01

We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...

Phase II trial of vindesine in patients with acute leukemia.

Science.gov (United States)

Sklaroff, R B; Arlin, Z; Young, C W

1979-01-01

Vindesine was administered to 18 patients with acute leukemia who had failed conventional chemotherapy. Each course of therapy consisted of an iv bolus infusion at a dose of 1-2 mg/m2 given daily x 5-10 days. Of 13 patients with acute lymphoblastic leukemia, two had partial remissions which lasted 2 and 3 months and five had minor responses. One of three patients with acute nonlymphoblastic leukemia and one of two patients with blastic crisis of chronic myelogenous leukemia each had a minor response. The data suggest that vindesine has activity in the treatment of acute leukemia.

A case of acute myelogenous leukemia occurring 8 years following 131I therapy for hyperthyroidism

International Nuclear Information System (INIS)

Sugiyama, Hiroyuki; Shimada, Hideto; Senzaki, Shigeki; Takahashi, Takayuki; Horiuchi, Tetsuo; Hoshino, Takashi

1982-01-01

A case of acute myelogenous leukemia occurring 8 years after 131 I therapy for hyperthyroidism is described. The patient, a man, was diagnosed as Hashitoxicosis in 1971 when ha was 62 years old, and was treated with 8 mCi of 131 I followed by antithyroid drug, propylthiouracil, without significant effect. In May 1979, he returned with complaints of malaise and loss of weight. Hematological examinations revealed pancytopenia and bone marrow hypoplasia with marked increase in myeloblasts, which suggested he was in a state of hypoplastic leukemia. Two months later, however, he developed an overt type of acute myelogenous leukemia. Combination chemotherapy was given without success to induce complete remission, and the patient died of pneumonia in November, 1979. (J.P.N.)

Case of acute myelogenous leukemia occurring 8 years following /sup 131/I therapy for hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Sugiyama, H.; Shimada, H.; Senzaki, S.; Takahashi, T.; Horiuchi, T.; Hoshino, T. (Kyoto Univ. (Japan). Faculty of Medicine)

1982-03-01

A case of acute myelogenous leukemia occurring 8 years after /sup 131/I therapy for hyperthyroidism is described. The patient, a man, was diagnosed as Hashitoxicosis in 1971 when ha was 62 years old, and was treated with 8 mCi of /sup 131/I followed by antithyroid drug, propylthiouracil, without significant effect. In May 1979, he returned with complaints of malaise and loss of weight. Hematological examinations revealed pancytopenia and bone marrow hypoplasia with marked increase in myeloblasts, which suggested he was in a state of hypoplastic leukemia. Two months later, however, he developed an overt type of acute myelogenous leukemia. Combination chemotherapy was given without success to induce complete remission, and the patient died of pneumonia in November, 1979.

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)...... of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.Leukemia advance online publication, 8 August 2017; doi:10.1038/leu.2017.213....

Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Bohnstedt, C; Levinsen, M; Rosthøj, S

2013-01-01

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology...

The MLL recombinome of acute leukemias in 2013

DEFF Research Database (Denmark)

Meyer, C; Hofmann, Julian; Burmeister, T

2013-01-01

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......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...

Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

Science.gov (United States)

Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

2014-01-01

Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

2018-01-01

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...

Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

2016-01-01

PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

Thromboembolism in Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Rank, Cecilie Utke; Toft, Nina; Tuckuviene, Ruta

2018-01-01

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during treatment of 1772 consecutive Nordic/Baltic ALL patients 1-45years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL...

Secondary acute leukemia - review of 15 cases

Energy Technology Data Exchange (ETDEWEB)

Venugopal, P; Rajni, A; Gopal, R; Saikia, T; Kurkure, P A; Nair, C N; Advani, S H

1988-12-01

Acute leukemia is a rare complication of long-term chemotherapy, immunosuppressive therapy and radiotherapy. With improved survival in cancer patients resulting from modern methods of investigations and treatment, more case of secondary leukemia have come to light. In this review, fifteen cases of secondary leukemia, its prognostic implications and methods to reduce the risk of its development are emphasised. Relevant literature is also reviewed. (author). 3 tabs., 24 refs.

Therapies for acute myeloid leukemia: vosaroxin

Directory of Open Access Journals (Sweden)

Sayar H

2017-08-01

Full Text Available Hamid Sayar,1 Parvaneh Bashardoust2 1Indiana University Simon Cancer Center, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 2Oceania University of Medicine, OUM-North America, Indianapolis, IN, USA Abstract: Vosaroxin, a quinolone-derivative chemotherapeutic agent, was considered a promising drug for the treatment of acute myeloid leukemia (AML. Early-stage clinical trials with this agent led to a large randomized double-blind placebo-controlled study of vosaroxin in combination with intermediate-dose cytarabine for the treatment of relapsed or refractory AML. The study demonstrated better complete remission rates with vosaroxin, but there was no statistically significant overall survival benefit in the whole cohort. A subset analysis censoring patients who had undergone allogeneic stem cell transplantation, however, revealed a modest but statistically significant improvement in overall survival particularly among older patients. This article reviews the data available on vosaroxin including clinical trials in AML and offers an analysis of findings of these studies as well as the current status of vosaroxin. Keywords: AML, acute myeloid leukemia, vosaroxin, SNS-595, cytarabine

Analysis of peroxidase-negative acute unclassifiable leukemias by monoclonal antibodies. 1. Acute myelogenous leukemia and acute myelomonocytic leukemia.

Science.gov (United States)

Imamura, N; Tanaka, R; Kajihara, H; Kuramoto, A

1988-11-01

In this study, pretreatment peripheral and/or bone marrow blasts from 12 patients with acute unclassifiable leukemia (AUL) expressing the myeloid-related cell-surface antigen (CD 11) were isolated for further analysis. Despite a lack of myeloperoxidase (MPO) activity, 1 patient's blasts contained cytoplasmic Auer rods. The circulating blasts from another patient expressed MPO while maintaining the same surface phenotype during 20 months of clinical follow-up. In addition, the blasts from 3 cases demonstrated both myelomonocytic and monocyte-specific surface antigens, whereas the remaining 9 cases completely lacked any monocyte-specific antigen detectable by monoclonal antibodies, Mo2, My4 and Leu M3 (CD 14). The first case eventually was diagnosed as acute myelomonocytic leukemia and the second as acute myelogenous leukemia by means of immunophenotypic analysis using flow cytometry (FACS IV). In addition, the presence of MPO protein was identified in the cytoplasm of blast cells from 5 patients with AUL by means of a cytoplasmic immunofluorescence test using a monoclonal antibody (MA1). Our study indicates that non-T, non-B AUL expressing OKM1 (CD 11) antigens include acute leukemias which are unequivocally identifiable as being of either myeloid or myelomonocytic origin. However, further investigations, including immunophenotypic and cytoplasmic analysis, ultrastructural cytochemistry and gene analysis with molecular probes (tests applicable to normal myeloid cells), are necessary in order to determine the actual origin of blasts and to recognize the differentiation stages of the various types of leukemic cells from patients with undifferentiated forms of leukemia.

Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Mingxue Fan

2017-08-01

Full Text Available Abstract Currently, conventional therapies for acute myeloid leukemia (AML have high failure and relapse rates. Thus, developing new strategies is crucial for improving the treatment of AML. With the clinical success of anti-CD19 chimeric antigen receptor (CAR T cell therapies against B-lineage malignancies, many studies have attempted to translate the success of CAR T cell therapy to other malignancies, including AML. This review summarizes the current advances in CAR T cell therapy against AML, including preclinical studies and clinical trials, and discusses the potential AML-associated surface markers that could be used for further CAR technology. Finally, we describe strategies that might address the current issues of employing CAR T cell therapy in AML.

PROGRESS IN ACUTE MYELOID LEUKEMIA

Science.gov (United States)

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases

International Nuclear Information System (INIS)

Cadman, E.C.; Capizzi, R.L.; Bertino, J.R.

1977-01-01

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p < 0.0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were threated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival

High-throughput profiling of signaling networks identifies mechanism-based combination therapy to eliminate microenvironmental resistance in acute myeloid leukemia.

Science.gov (United States)

Zeng, Zhihong; Liu, Wenbin; Tsao, Twee; Qiu, YiHua; Zhao, Yang; Samudio, Ismael; Sarbassov, Dos D; Kornblau, Steven M; Baggerly, Keith A; Kantarjian, Hagop M; Konopleva, Marina; Andreeff, Michael

2017-09-01

The bone marrow microenvironment is known to provide a survival advantage to residual acute myeloid leukemia cells, possibly contributing to disease recurrence. The mechanisms by which stroma in the microenvironment regulates leukemia survival remain largely unknown. Using reverse-phase protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment. Stroma reprogrammed signaling networks and modified the sensitivity of acute myeloid leukemia samples to all three targeted inhibitors. Stroma activated AKT at Ser473 in the majority of samples treated with single-agent ABT737 or Nutlin-3a. This survival mechanism was partially abrogated by concomitant treatment with temsirolimus plus ABT737 or Nutlin-3a. Mapping the signaling networks revealed that combinations of two inhibitors increased the number of affected proteins in the targeted pathways and in multiple parallel signaling, translating into facilitated cell death. These results demonstrated that a mechanism-based selection of combined inhibitors can be used to guide clinical drug selection and tailor treatment regimens to eliminate microenvironment-mediated resistance in acute myeloid leukemia. Copyright© 2017 Ferrata Storti Foundation.

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

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

2013-01-01

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 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. PMID:23628958

TARGETED NANOPARTICLES FOR PEDIATRIC LEUKEMIA THERAPY

Directory of Open Access Journals (Sweden)

Riyaz eBasha

2014-05-01

Full Text Available The two major forms of leukemia, acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML account for about one third of the malignancies diagnosed in children. Despite the marked successes in ALL and AML treatment, concerns remain regarding the occurrence of resistant disease in subsets of patients the residual effects of therapy that often persist for decades beyond the cessation of treatment. Therefore, new approaches are needed to reduce or to avoid off target toxicities, associated with chemotherapy and their long term residual effects. Recently, nanotechnology has been employed to enhance cancer therapy, via improving the bioavailability and therapeutic efficacy of anti-cancer agents. While in the last several years, numerous review articles appeared detailing the size, composition, assembly and performance evaluation of different types of drug carrying nanoparticles, the description and evaluation of lipoprotein based drug carriers have been conspicuously absent from most of these major reviews. The current review focuses on such information regarding nanoparticles with an emphasis on high density lipoprotein (HDL-based drug delivery systems to examine their potential role(s in the enhanced treatment of children with leukemia.

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood acute myeloid leukemia and other myeloid malignancies treatment may include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Learn more about AML and myelodysplastic/myeloproliferative diseases in this expert-reviewed summary.

Myeloblastic and lymphoblastic markers in acute undifferentiated leukemia and chronic myelogenous leukemia in blast crisis.

Science.gov (United States)

Shumak, K H; Baker, M A; Taub, R N; Coleman, M S

1980-11-01

Blast cells were obtained from 17 patients with acute undifferentiated leukemia and 13 patients with chronic myelogenous leukemia in blast crisis. The blasts were tested with anti-i serum in cytotoxicity tests and with antisera to myeloblastic leukemia-associated antigens in immunofluorescence tests. The terminal deoxynucleotidyl transferase (TDT) content of the blasts was also measured. Lymphoblasts react strongly with anti-i, do not react with anti-myeloblast serum, and have high levels of TDT; myeloblasts react weakly with anti-i, do not react with anti-myeloblast serum, and have very low levels of TDT. Of the 17 patients with acute undifferentiated leukemia, there were six with blasts which reacted like lymphoblasts, six with blasts which reacted like myeloblasts, and five with blasts bearing different combinations of these lymphoblastic and myeloblastic markers. Eight of the 11 patients with lymphoblastic or mixed lymphoblastic-myeloblastic markers, but only one of the six with myeloblastic markers, achieved complete or partial remission in response to therapy. Thus, in acute undifferentiated leukemia, classification of blasts with these markers may be of prognostic value. Of the 13 patients with chronic myelogenous leukemia in blast crises, the markers were concordant (for myeloblasts) in only two cases. Three of the 13 patients had TDT-positive blasts, but the reactions of these cells with anti-i and with anti-myeloblast serum differed from those seen with lymphoblasts from patients with acute lymphoblastic leukemia. Although the cell involved in "lymphoid" blast crisis of chronic myelogenous leukemia is similar in many respects to that involved in acute lymphoblastic leukemia, these cells are not identical.

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.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

International Nuclear Information System (INIS)

Michels, S.D.; McKenna, R.W.; Arthur, D.C.; Brunning, R.D.

1985-01-01

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy

SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

Science.gov (United States)

2013-01-10

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

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment.

Science.gov (United States)

Cernan, Martin; Szotkowski, Tomas; Pikalova, Zuzana

2017-09-01

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Global Characteristics of Childhood Acute Promyelocytic Leukemia

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Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

2014-01-01

Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

Science.gov (United States)

Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

2015-01-01

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

Directory of Open Access Journals (Sweden)

Guldane Cengiz Seval

2015-03-01

Full Text Available The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML in adolescent and young adult patients (AYAs may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

Acute myeloid leukemia: advancing clinical trials and promising therapeutics

Science.gov (United States)

Daver, Naval; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad

2016-01-01

Recent progress in understanding the biology of acute myeloid leukemia (AML) and the identification of targetable driver mutations, leukemia specific antigens and signal transduction pathways has ushered in a new era of therapy. In many circumstances the response rates with such targeted or antibody-based therapies are superior to those achieved with standard therapy and with decreased toxicity. In this review we discuss novel therapies in AML with a focus on two major areas of unmet need: (1) single agent and combination strategies to improve frontline therapy in elderly patients with AML and (2) molecularly targeted therapies in the frontline and salvage setting in all patients with AML. PMID:26910051

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

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Kimura, Shun-Ichi; Fujita, Hiroyuki; Kato, Hideaki; Hiramoto, Nobuhiro; Hosono, Naoko; Takahashi, Tsutomu; Shigeno, Kazuyuki; Hatsumi, Naoko; Minamiguchi, Hitoshi; Miyatake, Junichi; Handa, Hiroshi; Akiyama, Nobu; Kanda, Yoshinobu; Yoshida, Minoru; Kiyoi, Hitoshi; Miyazaki, Yasushi; Naoe, Tomoki

2017-11-01

We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

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

Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

Science.gov (United States)

Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

2015-12-01

Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

Esterase reactions in acute myelomonocytic leukemia.

Science.gov (United States)

Kass, L

1977-05-01

Specific and nonspecific esterase reactions of bone marrow cells from 14 patients with untreated acute myelomonocytic leukemia and six patients with acute histiomonocytic leukemia were examined. The technic for esterase determination permitted simultaneous visualization of both esterases on the same glass coverslip containing the marrow cells. In cases of acute histiomonocytic leukemia, monocytes, monocytoid hemohistioblasts and undifferentiated blasts stained intensely positive for nonspecific esterase, using alpha-naphthyl acetate as the substrate. No evidence of specific esterase activity using naphthol ASD-chloroacetate as the substrate and fast blue BBN as the dye coupler was apparent in these cells. In all of the cases of acute myelomonocytic leukemia, both specific and nonspecific esterases were visualized within monocytes, monocytoid cells, and granulocytic cells that had monocytoid-type nuclei. Nonspecific esterase activity was not observed in polymorphonuclear leukocytes in cases of myelomonocytic leukemia. The results support a current viewpoint that acute myelomonocytic leukemia may be a variant of acute myeloblastic leukemia, and that cytochemically, many of the leukemic cells in myelomonocytic leukemia share properties of both granulocytes and monocytes.

A Jehovah’s Witness with Acute Myeloid Leukemia Successfully Treated with an Epigenetic Drug, Azacitidine: A Clue for Development of Anti-AML Therapy Requiring Minimum Blood Transfusions

Directory of Open Access Journals (Sweden)

Yumi Yamamoto

2014-01-01

Full Text Available Therapy for acute leukemia in Jehovah’s Witnesses patients is very challenging because of their refusal to accept blood transfusions, a fundamental supportive therapy for this disease. These patients are often denied treatment for fear of treatment-related death. We present the first Jehovah’s Witness patient with acute myeloid leukemia (AML treated successfully with azacitidine. After achieving complete remission (CR with one course of azacitidine therapy, the patient received conventional postremission chemotherapy and remained in CR. In the case of patients who accept blood transfusions, there are reports indicating the treatment of AML patients with azacitidine. In these reports, azacitidine therapy was less toxic, including hematoxicity, compared with conventional chemotherapy. The CR rate in azacitidine-treated patients was inadequate; however, some characteristics could be useful in predicting azacitidine responders. The present case is useful for treating Jehovah’s Witnesses patients with AML and provides a clue for anti-AML therapy requiring minimum blood transfusions.

Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

Science.gov (United States)

Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

2003-12-01

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

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....

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

2018-02-01

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.

Acute Lymphoblastic Leukemia (ALL) (For Parents)

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... Staying Safe Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) What's in this article? About Leukemia Causes ...

Therapy-related myeloid neoplasm in an 18-year-old boy with B-lymphoblastic leukemia.

Science.gov (United States)

Qing, Xin; Panosyan, Eduard; Yue, Changjun; Ji, Ping; Gotesman, Moran; French, Samuel; Cai, Junchao

2017-12-01

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Acute myeloid leukemia or myelodysplastic syndrome during the course of ALL is a rare entity. Some of these cases are therapy-related while the others occur due to lineage switch. The correct diagnosis relies on comparing the immunophenotypes and cytogenetic/molecular alterations of the myeloid neoplasm and the ALL. We present the clinical, pathologic and cytogenetic features of a case of an 18-year-old male with prior treatment for B-lymphoblastic leukemia (B-ALL) who developed therapy-related myeloid neoplasm (t-MN) 4-5years after his initial diagnosis of B-ALL. A 13-year-old boy with no significant past medical history presented to Harbor-UCLA Medical Center (HUMC) in November 2012 with night sweats, fevers and chills, nausea, vomiting, diarrhea, fatigue, weakness, and weight loss. Peripheral blood flow cytometric analysis disclosed B-ALL. The blasts expressed CD10, CD19, CD22 (dim), CD34, CD38, HLA-DR, and TdT, and were negative for CD20, CD13, CD33, CD117, and cytoplasmic MPO. Chromosomal analysis and a supplemental fluorescence in situ hybridization (FISH) study performed on the bone marrow aspirate showed an abnormal karyotype (47,XY,+X,del(9)(p21p21)[4]/46,XY[16]). He achieved remission after induction chemotherapy and remained in remission until March 2016 when bilateral testicular masses were noted. Biopsy of the left testicular mass showed relapsed B-ALL. Cerebrospinal fluid (CSF) contained rare TdT-positive blasts, suggestive of minimal/early involvement by B-ALL. However, there was no evidence of acute leukemia in his bone marrow at this time. He was then treated with COG protocol AALL1331 randomized to blinatumomab arm and achieved second remission. In June 2017, the patient's peripheral blood smear showed 11% circulating monoblasts. By flow cytometry, the blasts expressed CD4, CD11b, CD13, CD15, CD33, CD38, CD56, and CD64. In addition, a few TdT-positive blasts were seen in

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...

[Acute myeloid leukemia].

Science.gov (United States)

Tabuchi, Ken

2007-02-01

The annual incident rate of pediatric acute myeloid leukemia (AML) is now 10 per million in Japan, against 5 to 9 per million in the USA and Europe. Overall long-term survival has now been achieved for more than 50% of pediatric patients with AML in the USA and in Europe. The prognostic factors of pediatric AML were analyzed,and patients with AML were classified according to prognostic factors. The t(15;17), inv(16) and t(8;21) have emerged as predictors of good prognosis in children with AML. Monosomy 7, monosomy 5 and del (5 q) abnormalities showed a poor prognosis. In addition to chromosomal deletions, FLT 3/ITD identifies pediatric patients with a particularly poor prognosis. Clinical trials of AML feature intensive chemotherapy with or without subsequent stem cell transplantation. Risk group stratification is becoming increasingly important in planning AML therapy. APL can be distinguished from other subtypes of AML by virtue of its excellent response and overall outcome as a result of differentiation therapy with ATRA. Children with Down syndrome and AML have been shown to have a superior prognosis to AML therapy compared to other children with AML. The results of the Japan Cooperative Study Group protocol ANLL 91 was one of the best previously reported in the literature. With the consideration of quality of life (QOL), risk-adapted therapy was introduced in the AML 99 trial conducted by the Japanese Childhood AML Cooperative Study Group. A high survival rate of 79% at 3 years was achieved for childhood de novo AML in the AML 99 trial. To evaluate the efficacy and safety of the treatment strategy according to risk stratification based on leukemia cell biology and response to the initial induction therapy in children with AML, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) has organized multi-center phase II trials in children with newly diagnosed AML.

Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.

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Nathalie Itzhar

Full Text Available Therapy-related acute leukemia (t-AML, is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML. Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case. In primary leukemia with a previously "normal" karyotype, 18% exhibited a previously undetected CNA, whereas in the (few t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40 kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1 Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML.

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

DEFF Research Database (Denmark)

Craddock, Charles; Labopin, Myriam; Robin, Marie

2016-01-01

Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Treatment options for adult acute myeloid leukemia (AML) include chemotherapy, radiation therapy, stem cell transplant, and other medications. Get detailed information about the treatment of new and recurrent AML in this expert-reviewed summary.

Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

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Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

2015-01-01

Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy

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Kohei Kasahara

2016-01-01

Full Text Available We report a case of acute myeloid leukemia (AML with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL. Initial G-band analysis showed 51,XY,+6,+8,inv(9(p12q13c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9(p12q13c[19]/46,XY,inv(9(p12q13c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes　(AML-MRC with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy.

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...

Occupation, hobbies, and acute leukemia in adults.

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Terry, Paul D; Shore, David L; Rauscher, Garth H; Sandler, Dale P

2005-10-01

Occupational and industrial exposures have been implicated in the etiology of leukemia, yet uncertainty remains regarding potential high risk occupations. We examined the associations between self-reported occupations and hobbies and acute leukemia risk using data from 811 cases and 637 controls participating in a case-control study in the U.S. and Canada. We found that several occupations may increase the risk of acute leukemia, particularly occupations related to petroleum products, rubber, nuclear energy, munitions, plastics, and electronics manufacturing. Differences were noted according to histological type. Other occupations and hobbies were not clearly associated with risk.

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.

Prognostic significance of primary bone changes in children with acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Rajantie, J.; Jaeaeskelaeinen, J.; Perkkioe, M.; Siimes, M.A.

1985-01-01

In a period of 6.5 years, acute leukaemia was diagnosed in 140 children at our hospital: 137 children had long bone radiographs and 45 patients had bone lesions. Eleven of the 115 patients who had skull radiographs had osteolytic lesions and another four had wide sutures. No patients had bone changes at relapse or at cessation of 3 years' successful therapy. In acute lymphoblastic leukemia, the frequence of osseous lesions tended to be higher in patients in sub-groups with a more favourable prognosis. The duration of remission and survival times were higher in patients with ''leukemic'' long bones than in those without them (p<0.10 and <0.05, respectively). Changes in the skull could not be related to the outcome. We found no abnormalities in the bones of the eight patients with acute non-lymphoblastic leukemia. (orig.)

Acute myeloid leukemia (AML) - children

Science.gov (United States)

Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

Two cases of acute leukemia developed after therapeutic radiation for malignant tumors

International Nuclear Information System (INIS)

Takahashi, Naoki; Matsuo, Kakaru; Yamaguchi, Hiroshi; Tsuno, Sumio; Toyoda, Shigeki

1978-01-01

Report was made as to two cases of acute leukemia developed after therapeutic radiation for malignant tumors. Both cases were exposed to atomic-bomb at the places 4 and 3 km far from the center of explosion, and they did not suffer from injuries and acute symptoms due to radiation. Case 1. -A 78 year old man had a mass in a right hypogastric region in April of 1975. In March of 1976, he received laparotomy and was diagnosed as malignant schwannoma. He received radiation therapy with 4,600 R and MFC therapy. In February of 1977, a clinical diagnosis of erythroleukemia was made according to the findings by bone marrow puncture, and he died in March. Postmortem examination revealed that main lesions were malignant schwannoma, its metastases, and leukemia. Case 2. -A 51 year old woman had a finger-tip sized tumor in the left breast in November of 1965, and had a radical operation on the basis of a diagnosis of comedo sarcoma. After that she received 60 Co irradiation with 18,800 R, and she was admitted in December of 1971, because she was suspected of having leukemia. She died in January of 1972. Postmortem examination revealed acute myelocytic leukemia. It is suspected that the onset of erythroleukemia within one year after irradiation would be influenced by MFC therapy in addition to radiotherapy. It was thought that leukemia in Case 2 was influenced by radiotherapy rather than atomic-bomb radioactivity. (Serizawa, K.)

Acute leukemias of ambiguous lineage.

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Béné, Marie C; Porwit, Anna

2012-02-01

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called "leukemias of ambiguous lineage." The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome 11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most from rapid allogeneic hematopoietic stem cell transplantation.

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

Science.gov (United States)

Straus, D J; Mertelsmann, R; Koziner, B; McKenzie, S; de Harven, E; Arlin, Z A; Kempin, S; Broxmeyer, H; Moore, M A; Menendez-Botet, C J; Gee, T S; Clarkson, B D

1980-11-01

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Acute myeloid (myelogenous) leukemia (AML) treatment options include chemotherapy, radiation therapy, stem cell transplant, and other medications. Cytogenetic analysis helps predict treatment outcomes. Get detailed information about AML in this summary for clinicians.

Asparaginase-Associated toxicity in children with acute lymphoblastic leukemia

NARCIS (Netherlands)

N. Hijiya (Nobuko); I.M. van der Sluis (Inge)

2016-01-01

textabstractAsparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with

AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

Science.gov (United States)

2018-03-12

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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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.

Acute external otitis as debut of acute myeloid leukemia - A case and review of the literature.

Science.gov (United States)

Slengerik-Hansen, Joachim; Ovesen, Therese

2018-03-01

Acute leukemia is a well known childhood cancer. The relation between leukemia and otological symptoms has long been established but is highly rare as a debut symptom of leukemia. External otitis is a common condition affecting many children, and most cases are successively treated with topical medicine. Here we present a child with acute external otitis later shown to be the debut symptom of acute myeloid leukemia, to our knowledge the first specific case described. We have reviewed the literature to find red flags for suspicion of severe disease in case of acute external otitis. Copyright © 2018 Elsevier B.V. All rights reserved.

Therapy related-chronic myelomonocytic leukemia (CMML): Molecular, cytogenetic, and clinical distinctions from de novo CMML.

Science.gov (United States)

Patnaik, Mrinal M; Vallapureddy, Rangit; Yalniz, Fevzi F; Hanson, Curtis A; Ketterling, Rhett P; Lasho, Terra L; Finke, Christy; Al-Kali, Aref; Gangat, Naseema; Tefferi, Ayalew

2018-01-01

Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t-CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t-CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t-CMML in comparison to d-CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t-CMML independently and adversely impacted OS (P = .0001 HR 2.1 95% CI 1.4-3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P = .001, HR 2.4, 95% CI 1.5-3.7) and the GFM prognostic model (P < .0001, HR 2.15, 95% CI 1.5-3.7). In summary, we highlight the unique genetics and independent prognostic impact of t-CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t-MN. © 2017 Wiley Periodicals, Inc.

Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

Directory of Open Access Journals (Sweden)

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.

Monocytic leukemias.

Science.gov (United States)

Shaw, M T

1980-05-01

The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

Diagnostic value of CD117 in differential diagnosis of acute leukemias.

Science.gov (United States)

Ahmadi, Abbas; Poorfathollah, Ali-Akbar; Aghaiipour, Mahnaz; Rezaei, Mansour; Nikoo-ghoftar, Mahin; Abdi, Mohammad; Gharib, Alireza; Amini, Amir

2014-07-01

C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in normal hematopoiesis. It has been demonstrated that its expression extremely increases in leukemias with myeloid commitment. We analyzed findings on CD117 expression together with other myeloid related markers in 203 de novo acute leukemias, referred to Iranian immunophenotyping centers: Iranian Blood Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were characterized based on the French American British cooperative group (FAB) and European Group for Immunological Classification of Leukemias (EGIL). The cases comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive was found (p = 0.036). The calculated specificity for myeloid involvement was 100 % for CD117 and CD33, and 98 % for CD13 and CD15 (p acute leukemias.

Beyond CD19: Opportunities for future development of targeted immunotherapy in pediatric relapsed-refractory acute leukemia

Directory of Open Access Journals (Sweden)

Haneen eShalabi

2015-10-01

Full Text Available Chimeric antigen receptor (CAR T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell ALL, this mode of therapy has become a very attractive option for these patients with high risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia, and potential therapeutic targets for additional high risk populations, including T cell ALL, AML, and infant ALL.

Diagnosis and treatment of acute and chronic leukemia

International Nuclear Information System (INIS)

1978-01-01

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other neoplastic conditions of the reticuloendothelial system, lymphatic system, spleen, multiple myeloma, macroglobulinemia and other monoclonal gammopathies are excluded, and will be coveted by other Cancergrams now under development. This Cancergram includes abstracts concerning all clinical aspects of the disease, such as diagnosis and staging, supportive care, evaluation, and therapy. Animal models, tissue culture experiments, carcinogenesis and other pre-clinical studies are generally excluded, except for those considered to have direct clinical relevance

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.

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)

Trisomy 4 in a case of acute undifferentiated myeloblastic leukemia with hand-mirror cells.

Science.gov (United States)

Kao, Y S; McCormick, C; Vial, R

1990-04-01

A case of acute undifferentiated myelocytic leukemic with trisomy 4 is described. The patient is a 61-year-old woman who developed leukemia 4 1/2 years after receiving radiation therapy for uterine carcinoma. Many leukemic cells exhibited hand-mirror configuration after the bone marrow aspirate was left at room temperature overnight. The relationship between trisomy 4 and hand-mirror cells in acute myelocytic leukemia is unknown.

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...

Trisomy/tetrasomy 13 in seven cases of acute leukemia.

Science.gov (United States)

Sreekantaiah, C; Baer, M R; Morgan, S; Isaacs, J D; Miller, K B; Sandberg, A A

1990-11-01

We report the clinical presentation and the morphologic, histochemical, and immunophenotypic characteristics of seven patients with acute leukemia who had trisomy/tetrasomy 13 as the sole cytogenetic abnormality in their leukemia. Five patients had trisomy 13 at diagnosis of acute leukemia. All five of these patients had undifferentiated leukemias. The sixth patient, who had French-American-British (FAB) type M2 acute nonlymphocytic leukemia (ANLL), and the seventh patient with biphenotypic acute leukemia developed the trisomic clone as a new abnormality late in the course of their disease. A review of the literature revealed 28 previously reported hematologic malignancies with trisomy 13 or tetrasomy 13q as a solitary cytogenetic abnormality. Trisomy 13 appears to represent another rare but nonrandom cytogenetic abnormality in acute leukemia. In our series trisomy 13 is largely associated with acute leukemia with little myeloid or lymphoid differentiation.

Acute leukemia after successful chemotherapy for oat cell carcinoma

International Nuclear Information System (INIS)

Rose, V.L.; Keppen, M.D.; Eichner, E.R.; Pitha, J.V.; Murray, J.L.

1983-01-01

A report of acute myelomonocytic leukemia following successful therapy for oat cell carcinoma is presented. The patient had been treated with extensive cytotoxic and radiation therapy, and was without clinical evidence of disease at one year follow-up. Eighteen months later, a peripheral smear revealed numerous blasts with monocytoid characteristics. This unusual presentation is discussed and compared with several other cases appearing in the recent literature

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

Cytogenetic basis of acute myeloid leukemia.

Science.gov (United States)

Ford, J H; Pittman, S M; Singh, S; Wass, E J; Vincent, P C; Gunz, F W

1975-10-01

The chromosomes of 12 adult patients with acute leukemia were analyzed by conventional means and by Giemsa and centromeric banding techniques. Acute myeloblastic leukemia was diagnosed in 7, acute myelomonocytic leukemia in 2, and acute undifferentiated leukemia in 3. Bone marrow was aspirated from patients when in relapse or remission, and both euploid and aneuploid cells were examined. All patients showed trisomy no. 9 and many showed additional numerical or structural changes in some or all their cells. These changes included monosomy no. 21 and/or monosomy no. 8. The proportion of trisomy no. 9 cells was 30-50% in patients in full remission and up to 100% in patients in relapse; thus trisomy no. 9 might be an important marker of leukemic cells. A mechanism was proposed to explain the induction and selection of the trisomy no. 9 karotype.

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

Science.gov (United States)

2013-01-09

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); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

Analysis of immunophenotype in acute myeloid leukemia by multiparameter flow cytometry

International Nuclear Information System (INIS)

Gao Yanqun; Jin Haijie; Yan Pei; Wang Feifei; Li Xiaohong; Gao Chunji

2005-01-01

To evaluate the immunophenotype of acute leukemia patients, the surface and cytoplasmic antigen expression in 162 cases of acute leukemia were analyzed by multiparameter flow cytometry and CD45/SSC gating. The results showed that CDl17 (94.9%), CD13 (88.5%) and CD33(70.5%) were mainly expressed in ANLL patients; cCD79a(100%), CD19(92.1%) were chiefly expressed in B-ALL patients, and in T-ALL patients, cCD3(100%) and CD2(83.3%) were expressed; For the expression of lymphoid differentiation antigen Ly+ANLL, CD7 (56.2%) and CD19(31.2%) were chiefly found, and for myeloid antigen My+ALL, CD13(88. 9%) and CD33 (27.8%) were detected. In conclusion, multiparameter flow cytometry and three-color direct immunofluorescence staining methods may be of important clinical significance in diagnosis, therapy and prognosis of acute leukemia. (authors)

Acute leukemia in early childhood

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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.

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

Second acute leukemia and other malignancies following treatment for Hodgkin's disease

International Nuclear Information System (INIS)

Valagussa, P.; Santoro, A.; Fossati-Bellani, F.; Banfi, A.; Bonadonna, G.

1986-01-01

The records of 1329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives

Cytosine arabinoside influx and nucleoside transport sites in acute leukemia.

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Wiley, J S; Jones, S P; Sawyer, W H; Paterson, A R

1982-02-01

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells, since mean influxes for myeloblasts and lymphoblasts were 6- and 2.3-fold greater than polymorphs and lymphocytes, respectively. Also, the mean influx for myeloblasts was fourfold greater than the mean for lymphoblasts. The number of nucleoside transport sites was estimated for each cell type by measuring the equilibrium binding of [(3)H]nitrobenzylthioinosine (NBMPR), which inhibits nucleoside fluxes by binding with high affinity to specific sites on the transport mechanism. The mean binding site numbers for myeloblasts and lymphoblasts were 5- and 2.8-fold greater, respectively, than for the mature cells of the same maturation series. The mean number of NBMPR binding sites for myeloblasts was fourfold greater than for lymphoblasts. Patients with AUL were heterogeneous since blasts from some gave values within the myeloblastic range and others within the lymphoblastic range. The araC influx correlated closely with the number of NBMPR binding sites measured in the same cells on the same day. Transport parameters were measured on blasts from 15 patients with AML or AUL who were then treated with standard induction therapy containing araC. Eight patients entered complete remission, while seven failed therapy, among whom were the three patients with the lowest araC influx (myeloblasts have both higher araC transport rates and more nucleoside transport sites than lymphoblasts and this factor may contribute to the greater sensitivity of AML to this drug. AraC transport varied >10

Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

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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.

Perceived Benefits and Barriers to Exercise for Recently Treated Adults With Acute Leukemia.

Science.gov (United States)

Leak Bryant, Ashley; Walton, AnnMarie L; Pergolotti, Mackenzi; Phillips, Brett; Bailey, Charlotte; Mayer, Deborah K; Battaglini, Claudio

2017-07-01

To explore perceived exercise benefits and barriers in adults with acute leukemia who recently completed an inpatient exercise intervention during induction therapy.
. Descriptive, exploratory design using semistructured interviews.
. Inpatient hematology/oncology unit at North Carolina Cancer Hospital in Chapel Hill.
. 6 adults with acute leukemia aged 35-67 years.
. Content analyses of semistructured interviews that were conducted with each participant prior to hospital discharge.
. Most participants were not meeting the recommended physical activity levels of 150 minutes of moderate-intensity exercise per week before their diagnosis. Patients were highly pleased with the exercise intervention and the overall program. Common barriers to exercise were anxiety and aches and pains.
. Overall, participants experienced physical and psychological benefits with the exercise intervention with no adverse events from exercising regularly during induction chemotherapy. Referrals for cancer rehabilitation management will lead to prolonged recovery benefits.
. Findings inform the nurses' role in encouraging and supporting adults with acute leukemia to exercise and be physically active during their hospitalization. Nurses should also be responsible for assisting patients with physical function activities to increase mobility and enhance overall health-related quality of life.

Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in Child with Acute Lymphoblastic Leukemia

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Olga Zając-Spychała

2016-01-01

Full Text Available Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by “probable” invasive fungal infection, when fungal pathogen is still uncertain. We report a case of probable hepatic candidiasis in 4-year-old boy with acute lymphoblastic leukemia. Despite proper antifungal therapy, there was no clinical and radiological improvement, so diagnosis of Candida-related IRIS was made and corticosteroid therapy was added to antifungal treatment achieving prompt resolution of infection symptoms.

Frank hematuria as the presentation feature of acute leukemia

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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.

Therapies for acute myeloid leukemia: vosaroxin.

Science.gov (United States)

Sayar, Hamid; Bashardoust, Parvaneh

2017-01-01

Vosaroxin, a quinolone-derivative chemotherapeutic agent, was considered a promising drug for the treatment of acute myeloid leukemia (AML). Early-stage clinical trials with this agent led to a large randomized double-blind placebo-controlled study of vosaroxin in combination with intermediate-dose cytarabine for the treatment of relapsed or refractory AML. The study demonstrated better complete remission rates with vosaroxin, but there was no statistically significant overall survival benefit in the whole cohort. A subset analysis censoring patients who had undergone allogeneic stem cell transplantation, however, revealed a modest but statistically significant improvement in overall survival particularly among older patients. This article reviews the data available on vosaroxin including clinical trials in AML and offers an analysis of findings of these studies as well as the current status of vosaroxin.

Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

2009-01-01

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...... acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P...

Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites

DEFF Research Database (Denmark)

Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N.

2017-01-01

BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy...... in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy. PROCEDURE: In children with ALL treated in Denmark according to the NOPHO ALL2008 protocol...... children receiving PEG-asparaginase biweekly, 29 developed SOS (≥2 criteria: hyperbilirubinemia, hepatomegaly, ascites, weight gain ≥2.5%, unexplained thrombocytopenia

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.

Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

DEFF Research Database (Denmark)

Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

Refractory acute promyelocytic leukemia successfully treated with combination therapy of arsenic trioxide and tamibarotene: A case report

Directory of Open Access Journals (Sweden)

Minoru Kojima

2016-01-01

Full Text Available A 40-year-old male developed refractory acute promyelocytic leukemia (APL after various treatments including all-trans retinoic acid, tamibarotene, arsenic trioxide (As2O3, conventional chemotherapy, and autologous peripheral blood stem cell transplantation. We attempted to use both tamibarotene and As2O3 as a combination therapy, and he achieved molecular complete remission. Grade 2 prolongation of the QTc interval on the electrocardiogram was observed during the therapy. The combination therapy of As2O3 and tamibarotene may be effective and tolerable for treating refractory APL cases who have no treatment options, even when they have previously been treated with tamibarotene and As2O3 as a single agent.

Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia

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Amy N. Sexauer

2017-11-01

Full Text Available Acute myeloid leukemia (AML is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3 occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses. Identification and development of targeted FLT3 inhibitors represents a major precision medicine paradigm shift in the treatment of patients with AML. While further development of many first-generation FLT3 inhibitors was hampered by limited potency and significant toxicity due to effects upon other kinases, the more selective second- and third-generation FLT3 inhibitors have demonstrated excellent tolerability and remarkable efficacy in the relapsed/refractory and now de novo FLT3-mutated AML settings. While these newest and most promising inhibitors have largely been studied in the adult population, pediatric investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing or planned. Successful development of FLT3 inhibitor-based therapies will be essential to improve outcomes in children with this high-risk subtype of AML.

Effects of Growth Hormone Therapy on Bone Mass, Metabolic Balance, and Well-Being in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

NARCIS (Netherlands)

van den Heijkant, Silvia; Hoorweg-Nijman, Gera; Huisman, Jaap; Drent, Madeleine; van der Pal, Heleen; Kaspers, Gert-Jan; Delemarre-van de Waal, Henriette

2011-01-01

Growth hormone deficiency (GHD), mostly after cranial radiotherapy (CRT), may lead to several negative effects. Young adult survivors of acute lymphoblastic leukemia (ALL) could benefit from GH therapy in different ways. Twenty ALL survivors (17.1 +/- 4.3 y after diagnosis) with low bone mineral

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since 1975. Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

Genetics Home Reference: core binding factor acute myeloid leukemia

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... binding factor acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Goyama S, Mulloy JC. Molecular ...

Management of acute lymphoblastic leukemia in young adults.

Science.gov (United States)

Muffly, Lori S; Reizine, Natalie; Stock, Wendy

2018-02-01

Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission. Blinatumomab, inotuzumab, and chimeric antigen receptor T-cell therapies are transforming the treatment of relapsed/refractory ALL. This comprehensive review of the current management of ALL in YAs summarizes recent scientific developments and clinical trial findings related to ALL biology, frontline management approaches, novel therapies, and supportive care specific to this patient population. Finally, a practical guide to modern YA management for practicing clinicians is provided.

Parvovirus B19 infection in a child with acute lymphoblastic leukemia during induction therapy.

Science.gov (United States)

McNall, R Y; Head, D R; Pui, C H; Razzouk, B I

2001-01-01

Immunocompromised children, including those undergoing chemotherapy treatment of malignant disease, are at particular risk for infection with parvovirus B19. However, these patients' attenuated immune responses may obscure the serologic and clinical manifestations of the infection. The authors describe a patient undergoing induction therapy for acute lymphoblastic leukemia whose parvovirus B19 infection was identified by the incidental detection of giant pronormoblasts and absence of normal mature erythroid precursors, characteristic of parvovirus infection, on a routine bone marrow examination. Intravenous immunoglobulin was administered and the patient's aplastic anemia resolved completely within 3 weeks. This highlights the importance of alertness to the possibility of parvovirus infection in children with cancer.

Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

International Nuclear Information System (INIS)

Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon

2014-01-01

To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

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Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

2014-09-15

To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

DEFF Research Database (Denmark)

Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.

2014-01-01

BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

2016-01-01

The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL......-negative blood isolates occurred more frequently in patients with a TE, and that lower incidences of BSI were detected in patients older than 9 years with a TE, and in patients with T-ALL. It is concluded that the type of CVC inserted at diagnosis has no impact upon the risk of BSI in patients with ALL...

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.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

Directory of Open Access Journals (Sweden)

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.

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

Translocations and deletions with breakpoint on 21q are nonrandomly associated with treatment-related acute nonlymphocytic leukemia and preleukemia

International Nuclear Information System (INIS)

Keldsen, N.; Philip, P.; Pedersen-Bjergaard, J.

1987-01-01

Six of 70 (8.6%) consecutive cases with therapy-related acute nonlymphocytic leukemia (ANLL) or preleukemia had a translocation or deletion with a breakpoint on 21q. Such aberrations were seen in only one of 200 (0.5%) consecutive cases of de novo ANLL examined at our laboratory. The figures reflect a 17.1-fold increased incidence of 21q aberrations in therapy-related ANLL or preleukemia, compared with ANLL de novo. The difference is highly significant (p = 0.003). The increased incidence of 21q aberrations in therapy-related myelodysplastic syndromes was confirmed by literature studies. Band 21q22 was most often involved. Cases with t(8;21), which is strongly associated with the M2 variant of ANLL, or cases with i(21q), which is supposedly due to a centromeric misdivision, were not included in the count. It is concluded that the 21q aberrations are associated with treatment-related ANLL or preleukemia with at least the same degree of specificity as aberrations of number5 and number7. 61 references

Radiotherapy of the central nervous system in acute leukemia

International Nuclear Information System (INIS)

Novak, L.J.

1989-01-01

The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.20 references

Case of acute myelogenous leukemia following aplastic anemia after radiotherapy and chemotherapy for breast cancer

Energy Technology Data Exchange (ETDEWEB)

Takano, Y; Chinen, T; Ogawa, M; Kato, Y; Kitagawa, T [Japanese Foundation for Cancer Research, Tokyo. Hospital

1980-12-01

A 53 years old mastectomized woman for breast cancer treated with radiotherapy (total doses 12,600 rad) and with long term oral administration of cyclophosphamide (CPM) and ftorafur (FT), developed aplastic anemia and thereafter acute myelogenous leukemia. About six months after discontinuation of the above therapies, she developed anemia and leukopenia and was referred to our clinic. Hematological improvement was obtained by the administration of anabolic hormone, however, two months later she became pancytopenic again. At that time, quite atypical myeloblasts contained peroxidase positive granules, were found 39% in the peripheral blood and 89.4% in the bone marrow, respectively. Leukemic hiatus was present. A bone marrow biopsy revealed coexistence of leukemic cells and breast cancer cells. A diagnosis of breast cancer complicated with acute myelogenous leukemia was made. A combined therapy of adriamycin, CPM and FT was ineffective. OAP regimen of vincristine, cytosine arabinoside and predonisolone revealed transient hematologic improvement. Finally, the patient died of septicemia due to klebsiella. Autopsy revealed wide spread coexistence of leukemia and cancer in the bone marrow, liver, and thyroid. The authors discuss some possible explanations for development of acute leukemia after radiotherapy and chemotherapy.

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

Recurrence of acute myeloid leukemia in cryptorchid testis: case report

International Nuclear Information System (INIS)

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, 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

Recurrence of acute myeloid leukemia in cryptorchid testis: case report

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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.

Haemostasis disturbances in children with acute lymphoblastic leukemia (ALL) - report of two cases

International Nuclear Information System (INIS)

Dus, M.; Samborska, M.; Derwich, K.

2009-01-01

The therapy of acute lymphoblastic leukemia (ALL) in children may be accompanied by numerous treatment-related complications of various etiology and severity. Possible adverse effects include thromboembolic and haemorrhagic events, which occur mainly during the induction or consolidation therapy, since as they are associated with the administration of L-Asparaginase (L-Asp), steroids and central venous access insertion. The aim of this report is to present haemostatic disturbances which occurred in 2 children with All, treated according to the ALL IC BFM 2002 regimen, despite prophylactic measures during intensive chemotherapy. (authors)

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.

Clinical Presentations of Acute Leukemia

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Shahab, F.; Raziq, F.

2014-01-01

Objective: To document the clinical presentation and epidemiology of various types of acute leukemia with their respective referral source at a tertiary level centre in Peshawar. Study Design: An observational study. Place and Duration of Study: Department of Pathology, Hayatabad Medical Complex (HMC), Peshawar, from January 2011 to May 2012. Methodology: A total of 618 bone marrow biopsy reports were reviewed. All biopsy reports labeled as acute leukemia were reviewed for age, gender, address, referring unit, diagnosis on bone marrow examination, presenting complaints, duration of illness and findings of clinical examination. Results: Ninety-two patients were diagnosed as suffering from acute leukemias (15%). ALL was most prevalent (46%), followed by AML (38%) and undifferentiated acute leukemia (16%). Males were affected more compared to females (60% vs. 40%). ALL and AML were predominant in pediatric (64%) and adults (77%) patients respectively. Patients from Afghanistan accounted for 33% of all cases followed by Peshawar (14%). Fever (77%), pallor (33%) and bleeding disorders (23%) were the main presenting complaints. Enlargement of liver, spleen and lymph nodes together was associated with ALL compared with AML (p = 0.004). Conclusion: ALL-L1 and AML-M4 were the most common sub-types. Fever, pallor and bleeding disorders were the main presenting complaints. Enlargement of liver, spleen and lymph nodes was more frequently associated with ALL compared to AML. (author)

Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

Science.gov (United States)

Bongiovanni, Deborah; Saccomani, Valentina

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease caused by the malignant transformation of immature progenitors primed towards T-cell development. Clinically, T-ALL patients present with diffuse infiltration of the bone marrow by immature T-cell blasts high blood cell counts, mediastinal involvement, and diffusion to the central nervous system. In the past decade, the genomic landscape of T-ALL has been the target of intense research. The identification of specific genomic alterations has contributed to identify strong oncogenic drivers and signaling pathways regulating leukemia growth. Notwithstanding, T-ALL patients are still treated with high-dose multiagent chemotherapy, potentially exposing these patients to considerable acute and long-term side effects. This review summarizes recent advances in our understanding of the signaling pathways relevant for the pathogenesis of T-ALL and the opportunities offered for targeted therapy. PMID:28872614

Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

Science.gov (United States)

Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

2013-08-01

While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients. Copyright © 2013 Wiley Periodicals, Inc.

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...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

The findings of F-18 FDG camera-based coincidence PET in acute leukemia

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Yoon, S. N.; Joh, C. W.; Lee, M. H. [Ajou University School of Medicine, Suwon (Korea, Republic of)

2002-07-01

We evaluated the usefulness of F-18 FDG coincidence PET (CoDe-PET) using a dual-head gamma camera in the assessment of patients with acute leukemia. F-18 FDG CoDE-PET studies were performed in 5 patients with acute leukemia (6 ALL and 2 AML) before or after treatment. CoDe-PET was performed utilizing a dual-head gamma camera equipped with 5/8 inch NaI(Tl) crystal. Image acquisition began 60 minutes after the injection of F-18 FDG in the fasting state. A whole trunk from cervical to inguinal regions or selected region were scanned. No attenuation correction was made and image reconstruction was done using filtered back-projection. CoDe-PET studies were evaluated visually. F-18 FDG image performed in 5 patients with ALL before therapy depicted multiple lymph node involvement and diffuse increased uptake involving axial skeleton, pelvis and femurs. F-18 FDG image done in 2 AML after chemotherapy showed only diffuse increased uptake in sternum, ribs, spine, pelvis and proximal femur and these may be due to G-CSF stimulation effect in view of drug history. But bone marrow histology showed scattered blast cell suggesting incomplete remission in one and completer remission in another. F-18 image done in 1 ALL after therapy showed no abnormal uptake. CoDe-PET with F-18 FDG in acute lymphoblastic lymphoma showed multiple lymphnode and bone marrow involvement in whole body. Therefore we conclude that CoDe-PET with F-18 FDG usefulness for evaluation of extent in acute lymphoblastic leukemia. But there was a limitation to assess therapy effectiveness during therapy due to reactive bone marrow.

Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

Science.gov (United States)

... Familial acute myeloid leukemia with mutated CEBPA Familial acute myeloid leukemia with mutated CEBPA Printable PDF Open All Close ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Carmichael CL, Wilkins EJ, ...

Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era

Science.gov (United States)

Ramadan, Safaa M.; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

2012-01-01

The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed. PMID:22689684

Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

Science.gov (United States)

Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

2014-01-01

Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia

DEFF Research Database (Denmark)

Østgård, Lene Sofie Granfeldt; Lund, Jennifer L; Nørgaard, Jan Maxwell

2018-01-01

To examine the outcome of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared to chemotherapy alone in a population-based setting, we identified a cohort of acute myeloid leukemia (AML) patients aged 15-70 years diagnosed between 2000-2014 in Denmark. Using...... the Danish National Acute Leukemia Registry, we compared relapse risk, relapse-free survival (RFS), and overall survival between patients with non-favorable cytogenetic features receiving post-remission therapy with conventional chemotherapy-only versus those undergoing HSCT in CR1. To minimize immortal time...

Phosphoproteomic profiling analysis in pediatric acute leukemias and in solid tumors of the adult

International Nuclear Information System (INIS)

Basso, G.; Nitti, D.

2009-01-01

We analyzed 120 pediatric patients affected with B-cell AL (B-Acute Lymphoblastic Leukemia) by Reverse Phase Protein Arrays (RPPA). Leukemia cells from bone marrow aspirates were stored in liquid nitrogen in the Bio Bank of the Laboratory of Pediatric Onco hematology in Padova. Clinical data, such as immuno phenotype, outcome, response to therapy and chromosomal translocations, were collected for all the patients

Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol)

International Nuclear Information System (INIS)

Siemes, H.; Rating, D.; Siegert, M.; Hanefeld, F.; Mueller, S.; Gadner, H.; Riehm, H.

1980-01-01

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown

Heterogeneity in acute undifferentiated leukemia.

Science.gov (United States)

LeMaistre, A; Childs, C C; Hirsch-Ginsberg, C; Reuben, J; Cork, A; Trujillo, J M; Andersson, B; McCredie, K B; Freireich, E; Stass, S A

1988-01-01

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.

An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

International Nuclear Information System (INIS)

Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

1990-01-01

Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

Genetics Home Reference: cytogenetically normal acute myeloid leukemia

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... Testing (1 link) Genetic Testing Registry: Acute myeloid leukemia Other Diagnosis and Management Resources (3 links) Fred Hutchinson Cancer Research Center National Cancer Institute: Acute Myeloid Leukemia Treatment St. Jude Children's Research Hospital General Information ...

IKAROS Gene Deleted B-Cell Acute Lymphoblastic Leukemia in Mexican Mestizos: Observations in Seven Patients and a Short Review of the Literature.

Science.gov (United States)

Ruiz-Delgado, Guillermo José; Cantero-Fortiz, Yahveth; León-Peña, Andrés Aurelio; León-González, Mónica; Nuñez-Cortés, Ana Karen; Ruiz-Argüelles, Guillermo José

2016-01-01

In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia. At a single center we prospectively studied patients diagnosed with B-cell acute lymphoblastic leukemia and screened for IKZF1 deletion using the multiplex ligation-dependent probe amplification method. We did a descriptive analysis of patients positive for the IKZF1 deletion to determine its impact on the evolution of the disease and survival rate. Between 2010 and 2015, 16 Mexican mestizo patients with B-cell acute lymphoblastic leukemia were prospectively screened for IKZF1 deletion; seven (43%) were positive and were included for further analysis. The age range of patients was 13-60 years; six were males and one female. All cases had type B acute lymphoblastic leukemia. Of the seven patients, two died, three were lost to follow-up, and two continue in complete remission with treatment. Results are worse than those in a group of patients with non-mutated IKAROS B-cell acute lymphoblastic leukemia previously studied in our center. Although this is a small sample, the presence of IKAROS deletion in acute lymphoblastic leukemia patients could represent a poor-prognosis marker and was probably related to therapy failure. It is also possible that this variant of leukemia may be more prevalent in Mexico. More studies are needed to define the role of IKZF1 deletion in acute lymphoblastic leukemia and the real prevalence of the disease in different populations.

Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Wojtuszkiewicz, Anna; Peters, Godefridus J; van Woerden, Nicole L

2015-01-01

BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblast...... resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients....... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...... in tumor cells, have been classified as determinants of MTX resistance. However, the relation between MTX resistance and long-term clinical outcome of ALL has not been shown previously. METHODS: We have collected clinical data for 235 childhood ALL patients, for whom samples taken at the time of diagnosis...

Infection pattern of neutropenic patients in post-chemotherapy phase of acute leukemia treatment

Directory of Open Access Journals (Sweden)

Ahmad Ahmadzadeh

2013-12-01

Full Text Available Neutropenia following chemotherapy regimens in leukemia patients is of major concern since it makes these patients vulnerable to infections. If we can identify which germs are causing these infections, they can be annihilated or, at least, the most appropriate antibiotic therapy can be started immediately, even before we have the results of the culture. This retrospective multi-center study took place in 2012 and included patients with acute leukemia who had already undergone chemotherapy and who had been febrile for at least 16 hours. In order to assess the type of infection, different environments were chosen and the results were compared by t-test and x2 tests. This study took place in four hospitals in Tehran and Ahwaz, Iran. The study population was made up of 89 patients: 37 with acute lymphoblastic leukemia and 52 with acute myeloid leukemia. The results revealed that blood was the most common site of infection. From all our positive cultures, it was seen that 85.4% of them had gram-negative bacteria with a dominance of E. coli of 25.8% over the other colonies. Also, antibiograms revealed the sensitivity of almost all the gram-negatives to amino glycosides. In contrast with most of the literature, in our patients, gram-negatives are the most common cause of infection and, therefore, administering amino glycosides would be the safest antibiotic therapy to prescribe before culture results are available.

Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features.

Science.gov (United States)

Reiffers, J; Bernard, P; Larrue, J; Dachary, D; David, B; Boisseau, M; Broustet, A

1985-01-01

This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.

[Prognostic significance of the cyclic AMP concentration in acute leukemias].

Science.gov (United States)

Paietta, E; Mittermayer, K; Schwarzmeier, J D

1979-01-01

In patients with acute leukemia (myeloblastic, lymphoblastic, undifferentiated) proliferation kinetics and cyclic adenosine-3', 5'-monophosphate (cAMP) concentration of the leukemic cells were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly faster turnover and lower cAMP-levels than those who failed to respond to treatment.

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.)

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.)

Minimal Residual Disease in Acute Myeloid Leukemia: Still a Work in Progress?

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Federico Mosna

2017-06-01

Full Text Available Minimal residual disease evaluation refers to a series of molecular and immunophenotypical techniques aimed at detecting submicroscopic disease after therapy. As such, its application in acute myeloid leukemia has greatly increased our ability to quantify treatment response, and to determine the chemosensitivity of the disease, as the final product of the drug schedule, dose intensity, biodistribution, and the pharmakogenetic profile of the patient. There is now consistent evidence for the prognostic power of minimal residual disease evaluation in acute myeloid leukemia, which is complementary to the baseline prognostic assessment of the disease. The focus for its use is therefore shifting to individualize treatment based on a deeper evaluation of chemosensitivity and residual tumor burden. In this review, we will summarize the results of the major clinical studies evaluating minimal residual disease in acute myeloid leukemia in adults in recent years and address the technical and practical issues still hampering the spread of these techniques outside controlled clinical trials. We will also briefly speculate on future developments and offer our point of view, and a word of caution, on the present use of minimal residual disease measurements in “real-life” practice. Still, as final standardization and diffusion of the methods are sorted out, we believe that minimal residual disease will soon become the new standard for evaluating response in the treatment of acute myeloid leukemia.

Recent advances in acute lymphoblastic leukemia in children and adolescents: an expert panel discussion.

Science.gov (United States)

Asselin, Barbara L; Gaynon, Paul; Whitlock, James A

2013-12-01

Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia, representing 75% to 80% of cases of acute leukemia among children. Dramatic improvements in the cure rates and survival outcomes for children with ALL have been seen over the past several decades; currently the 5-year survival rate for childhood ALL is more than 80%. These improvements have come about because of advances in the understanding of the molecular genetics and pathogenesis of the disease, incorporation of risk-adapted therapy, and the advent of new targeted agents. Scientific advances have provided new insights into leukemogenesis, drug resistance, and host pharmacogenomics, identified novel subtypes of leukemia, and suggested potential targets for therapy. At the same time novel monoclonal antibodies, small molecule inhibitors, chemotherapeutics, and cell-based treatment strategies have been developed and investigated. In this article, experts will discuss some of the current challenges and future directions in the treatment of pediatric ALL. The authors will offer expert guidance to practicing oncologists on how to best incorporate newer treatment approaches into the care of children and adolescents with ALL. The most important ongoing clinical trials in the area will also be reviewed.

Side effects of treatment in childhood acute leukemia, 2

International Nuclear Information System (INIS)

Fujinami, Akira; Murakami, Mako; Sako, Masahiro; Takubo, Yoshiyuki; Nakagawa, Kimiko; Konishi, Shouzaburo; Tsujino, Giiti; Hata, Shinn; Koizumi, Yoshiko

1989-01-01

We evaluated delayed neurotoxicities in treatment of childhood acute leukemia. Of 28 patients treated over 2 years who were examined on computed tomography of brain scans, 7 patients had abnormal findings. These abnormalities included two cases of leukoencephalopathy, three cases of intracranial calcifications, and two of ventricular dilatation. These patients were under 6 years old at the onset of disease, especially under 3 years old. Also, delayed neurotoxicities developed after relapse of leukemia, especially CNS relapse. It was considered that these were caused by cranial irradiation, intravenous methotrexate injection, intrathecal methotrexate, and sometimes high-dose Ara-C therapy, etc. Most of the cases of leukoencephalopathy were associated with treatment of intermediate-dose or high-dose methotrexate after relapse. These abnormalities must be carefully considered in the treatment of younger children with leukemia and patients with relapse. (author)

Biting back: BiTE antibodies as a promising therapy for acute myeloid leukemia.

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Walter, Roland B

2014-06-01

The experience with gemtuzumab ozogamicin has highlighted both the potential value and limitations of antibodies in acute myeloid leukemia (AML). Recently, bispecific T-cell engager (BiTE) antibodies have emerged as a means to harness polyclonal cytotoxic T-cells and cause highly efficient lysis of targeted tumor cells. Promising early results have been obtained with the CD19-directed BiTE antibody, blinatumomab, in patients with acute lymphoblastic leukemia. A first candidate for AML is the CD33/CD3 molecule, AMG 330, for which several recent preclinical studies demonstrated high potency and efficacy in destroying CD33(+) human AML cells. Many questions remain to be addressed, but BiTE antibodies may offer an exciting new tool in a disease for which the outcomes in many patients remain unsatisfactory.

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

2007-01-01

At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs...

Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

Science.gov (United States)

2018-02-16

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...NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD

Esterase Isoenzyme Profiles in Acute and Chronic Leukemias.

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Drexler, H G; Gignac, S M; Hoffbrand, A V; Minowada, J

1991-01-01

Using isoelectric focusing (IEF) a number of carboxylic esterase isoenzymes (EC 3.1.1.1) with isoelectric points between pH 4.5-8.0 can be separated. One particular isoenzyme with an isoelectric point at about pH 6.0, the Mono-band, can be selectively and completely inhibited by sodium fluoride; this isoenzyme comprises a number of closely related subcomponents and may appear in more than one band on the gel. We analyzed the expression of typical esterase isoenzyme patterns in cells from a large panel of leukemias which were tested under identical conditions by IEF on horizontal thin-layer polyacrylamide gels with an ampholyte of pH 2-11. The 442 cases of acute and chronic myeloid and lymphoid leukemia (AML/AMMoL, CML/CMML, ALL, CLL) were classified according to clinical, morpho-cytochemical and immunophenotyping criteria. While bands between pH 4.5-5.5 appeared not to be specific for lineage or stage of differentiation, isoenzymes between pH 6.6-7.7 provided information on the type of leukemia involved. Seven typical isoenzyme patterns termed Mono1/Mono2 (fo monocyte-associated), My1/My2 (myeloid), Lym1/Lym2 (lymphoid) and Und (undifferentiated) could be discerned. Lym and Und patterns are characterized by fewer bands with a weaker staining intensity than Mono and My patterns. Nearly all cases of lymphoid leukemias (acute and chronic) expressed only Lym or Und esterase isoenzyme patterns, but no Mono or My patterns. Cases of acute or chronic myeloid and (myelo)monocytic leukemia showed strong isoenzyme staining displaying predominantly Mono or My isoenzyme patterns. The isoenzyme patterns found in CML in lymphoid or myeloid blast crisis corresponded to those seen in the respective acute leukemias, ALL or AML. The Mono-band was found in most cases of leukemias with monocytic elements (AMMoL 80%, CML 44%, CMML 100%), in the occasional case of CML-myeloid blast crisis or AML, but in none of the cases of ALL or CLL. This isoenzyme is a distinctive, specific marker for

Adrenocortical function and reserve in children treated for acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Pawlaczyk, B.; Malecka, E.H.; Krause, W.

1993-01-01

Serum cortisol and 17 OHS, 17 KS and DHA levels in 24-hour urine were determined in 30 children (22 girls and boys) 0.5 to 4 years after completion of therapy (radio- and chemotherapy) for acute lymphoblastic leukemia (ALL). Serum cortisol after Syncthen (adrenocortical reserve) was determined in 15 girls and 4 boys. The results show that therapy for ALL depresses glucocorticosteroid synthesis; however, it does not disturb the adrenal reserve or androgenesis. (author)

Acute lymphoblastic leukemia: a comprehensive review and 2017 update

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Terwilliger, T; Abdul-Hay, M

2017-01-01

Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

Expression of CD133 in acute leukemia.

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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.

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

Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon

2009-01-01

The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy (P=0.04) were both related to an increased risk of an event (overall P value of the Cox model: 0.003), whereas neither sex, age at diagnosis, administration of central nervous system irradiation, nor presence of a day 15 bone marrow with > or =25% versus

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

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

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

Science.gov (United States)

Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

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 dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

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

Heterogeneity of acute myeloblastic leukemia without maturation: an ultrastructural study.

Science.gov (United States)

Hamamoto, K; Date, M; Taniguchi, H; Nagano, T; Kishimoto, Y; Kimura, T; Fukuhara, S

1995-01-01

We demonstrated by ultrastructural examination that the leukemic blasts of 13 patients with acute myeloblastic leukemia (AML) without maturation (M1 in the French-American-British classification) showed heterogeneous features. In 7 patients, the leukemic blasts had a high level of light microscopic myeloperoxidase positivity (> 50%). Ultrastructurally, the cells were myeloblast-promyelocytes with 100% myeloperoxidase positivity, and these 7 patients appeared to have typical AML. In contrast, the remaining 6 patients had leukemic blasts with a low myeloperoxidase positivity (undifferentiated blasts. The former group had a better prognosis than the latter, indicating that ultrastructural analysis of M1 leukemia may help predict the response to therapy.

Small Molecule Inhibitors in Acute Myeloid Leukemia: From the Bench to the Clinic

Science.gov (United States)

Al-Hussaini, Muneera; DiPersio, John F.

2014-01-01

Many patients with acute myeloid leukemia (AML) will eventually develop refractory or relapsed disease. In the absence of standard therapy for this population, there is currently an urgent unmet need for novel therapeutic agents. Targeted therapy with small molecule inhibitors (SMIs) represents a new therapeutic intervention that has been successful for the treatment of multiple tumors (e.g., gastrointestinal stromal tumors, chronic myelogenous leukemia). Hence, there has been great interest in generating selective small molecule inhibitors targeting critical pathways of proliferation and survival in AML. This review highlights a selective group of intriguing therapeutic agents and their presumed targets in both preclinical models and in early human clinical trials. PMID:25025370

Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

Energy Technology Data Exchange (ETDEWEB)

Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula [Ondokuz Mayis University, Samsun (Turkmenistan)

2009-10-15

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.

Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia

DEFF Research Database (Denmark)

Øvlisen, Andreas K; Oest, Anders; Bendtsen, Mette D

2018-01-01

Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission...... transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie,

CT findings of children with acute leukemia with special reference to 5 cases of leukoencephalopathy

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Hattori, Haruo; Akiyama, Yuichi; Takao, Tatsuo; Ito, Masatoshi; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

1983-10-01

CT scans of the brain were taken 122 times in 43 children with acute leukemia. CT evidence of cerebral atrophy was seen in 58.1% (25/43) of the children. Of the children who were studied during initial antileukemic therapy, such as remission-induction therapy and CNS prophylaxis, 67.7% (21/31) also had CT evidence of cerebral atrophy. This high incidence was considered mainly due to the administration of the glucocorticoid hormone during the remission-induction therapy. Leukoencephalopathy developed in 11.6% (5/43) of the children. These 5 cases had CNS leukemia, systemic or intrathecal methotrexate administration, or CNS irradiation; the common factor was intrathecal methotrexate administration. Low-density areas in the cerebral white matter, ventricular dilatation, and intracerebral calcification were found on CT. The distribution of these areas was symmetrical (periventricular lucency), asymmetrical, or focal. Only 2 of these 5 children had intracerebral calcification; they survived more than 5 years after the onset of acute leukemia. CT was useful in evaluating 2 other asymptomatic children with low-density areas in the cerebral white matter. This finding was suggestive of preclinical or subclinical leukoencephalopathy.

CT findings of children with acute leukemia with special reference to 5 cases of leukoencephalopathy

International Nuclear Information System (INIS)

Hattori, Haruo; Akiyama, Yuichi; Takao, Tatsuo; Ito, Masatoshi; Nakano, Shozo

1983-01-01

CT scans of the brain were taken 122 times in 43 children with acute leukemia. CT evidence of cerebral atrophy was seen in 58.1% (25/43) of the children. Of the children who were studied during initial antileukemic therapy, such as remission-induction therapy and CNS prophylaxis, 67.7% (21/31) also had CT evidence of cerebral atrophy. This high incidence was considered mainly due to the administration of the glucocorticoid hormone during the remission-induction therapy. Leukoencephalopathy developed in 11.6% (5/43) of the children. These 5 cases had CNS leukemia, systemic or intrathecal methotrexate administration, or CNS irradiation; the common factor was intrathecal methotrexate administration. Low-density areas in the cerebral white matter, ventricular dilatation, and intracerebral calcification were found on CT. The distribution of these areas was symmetrical (periventricular lucency), asymmetrical, or focal. Only 2 of these 5 children had intracerebral calcification; they survived more than 5 years after the onset of acute leukemia. CT was useful in evaluating 2 other asymptomatic children with low-density areas in the cerebral white matter. This finding was suggestive of preclinical or subclinical leukoencephalopathy. (author)

WHO HAS THERAPY-RELATED AML?

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Robert Gale

2017-03-01

Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

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

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

International Nuclear Information System (INIS)

Ding, Kai; Wang, Xiao-ming; Fu, Rong; Ruan, Er-bao; Liu, Hui; Shao, Zong-hong

2012-01-01

To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M 3 , 33.3% in M 2 , and 28.6% in M 5 . Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype, but not with age, gender, white blood count or percentage of blast cells. The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia

Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

Directory of Open Access Journals (Sweden)

Emmons Gregory S

2012-10-01

Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

Utility of peripheral blood immunophenotyping by flow cytometry in the diagnosis of pediatric acute leukemia.

Science.gov (United States)

Metrock, Laura K; Summers, Ryan J; Park, Sunita; Gillespie, Scott; Castellino, Sharon; Lew, Glen; Keller, Frank G

2017-10-01

Childhood acute leukemia is traditionally diagnosed from a bone marrow aspirate (BMA). New-onset acute leukemia patients do not always have visible circulating blasts in the peripheral blood (PB) at diagnosis. While the role of bone marrow flow cytometry for the diagnosis of acute leukemia is well established, the utility of PB flow cytometry (PBFC) is unknown. We performed a single-institution retrospective analysis to compare PBFC versus BMA in establishing or excluding a diagnosis of childhood acute leukemia. We retrospectively identified 485 PBFC samples with concurrent BMA from 2008 to 2013. Results of four-color flow cytometry for immunophenotypic characterization of leukemic versus nonclonal disease were characterized. Sensitivity and specificity were calculated among patients without a known diagnosis or prior therapy. Among 485 samples eligible for analysis, 120 had negative PBFC and BMA, 359 had positive PBFC and BMA, 3 had negative PBFC and positive BMA, and 3 had positive PBFC and negative BMA. There were small but significant differences in sensitivity (100 vs. 93.8%; P = 0.002) and positive predictive value (100 vs. 93.8%; P = 0.002) favoring BMA over PBFC among those demonstrating absence of circulating morphologic blasts. PBFC has high sensitivity and specificity for the diagnosis of childhood acute leukemia. The predictive value of PBFC remains high for patients without visible circulating blasts and may enhance the diagnostic process for determining the indications for marrow testing. © 2017 Wiley Periodicals, Inc.

WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy.

Science.gov (United States)

Rein, Lindsay A M; Chao, Nelson J

2014-03-01

The Wilms tumor 1 (WT1) gene was originally identified as a tumor suppressor gene that, when mutated, would lead to the development of pediatric renal tumors. More recently, it has been determined that WT1 is overexpressed in 90% of patients with acute myeloid leukemia (AML) and is mutated in approximately 10% of AML patients. WT1 plays a role in normal hematopoiesis and, in AML specifically, it has oncogenic function and plays an important role in cellular proliferation and differentiation. The ubiquity of WT1 in leukemia has lead to the development of vaccines aimed at employing the host immune system to mount a T-cell response to a known antigen. In this evaluation, the authors discuss the role of WT1 in normal hematopoiesis as well as in the development of hematologic malignancies. Furthermore, the authors discuss the data supporting the development of WT1 vaccines, and the clinical trials supporting their use in patients with acute leukemia. Several small trials have been conducted which support the safety and efficacy of this therapy, although larger trials are certainly warranted. In the authors' opinion, the WT1 vaccination has potential in terms of its application as an adjuvant therapy for patients with AML who are at high risk of relapse or who have detectable minimal residual disease after initial standard therapy.

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

Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

Directory of Open Access Journals (Sweden)

Chana L. Glasser, MD

2017-01-01

Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

DEFF Research Database (Denmark)

Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

2011-01-01

Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ...... hybridization for del(5q31). DESIGN AND METHODS: Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial...... the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4...

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

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Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

2006-03-15

Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

Karyotyping, FISH, and PCR in acute lymphoblastic leukemia: competing or complementary diagnostics?

NARCIS (Netherlands)

Olde Nordkamp, Louise; Mellink, Clemens; van der Schoot, Ellen; van den Berg, Henk

2009-01-01

BACKGROUND: Chromosomal abnormalities, such as t(9;22)(q34;q11) (ABL/BCR), t(12;21)(p13;q22) (TEL/AML1), and t(11q23) (MLL) are independent prognostic indicators in childhood acute lymphoblastic leukemia resulting in risk adapted therapy. Accurate and rapid detection of these abnormalities is

Frontline treatment of acute myeloid leukemia in adults

Science.gov (United States)

Tamamyan, Gevorg; Kadia, Tapan; Ravandi, Farhad; Borthakur, Gautam; Cortes, Jorge; Jabbour, Elias; Daver, Naval; Ohanian, Maro; Kantarjian, Hagop; Konopleva, Marina

2017-01-01

Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients’ age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40–50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30–40% up to 80–90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the “7+3” regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the “7+3” regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future. PMID:28109402

Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

DEFF Research Database (Denmark)

Schmiegelow, K; Nyvold, C; Seyfarth, J

2001-01-01

Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone......, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction...... pronounced when B cell precursor and T cell leukemia were analyzed separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47, P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P = 0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients...

ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

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Stuart P. Weisberg

2014-02-01

Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

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%.

Pictorial essay: Acute neurological complications in children with acute lymphoblastic leukemia

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Seema A Kembhavi

2012-01-01

Full Text Available Acute lymphoblastic leukemia (ALL is the commonest childhood malignancy with high cure rates due to recent advances in central nervous system (CNS prophylaxis. The disease per se, as well as the prophylactic therapy, predisposes the child to complications such as cerebrovascular events, infections, drug toxicities, etc. The purpose of this study is to highlight the pathophysiology and the imaging features (with appropriate examples of these complications and to propose a diagnostic algorithm based on MRI. Interpreting these scans in the light of clinical inputs very often helps the radiologist reach an appropriate diagnosis and help treatment and management.

Pictorial essay: Acute neurological complications in children with acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Kembhavi, Seema A.; Somvanshi, Snehal; Banavali, Shripad; Kurkure, Purna; Arora, Brijesh

2012-01-01

Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy with high cure rates due to recent advances in central nervous system (CNS) prophylaxis. The disease per se, as well as the prophylactic therapy, predisposes the child to complications such as cerebrovascular events, infections, drug toxicities, etc. The purpose of this study is to highlight the pathophysiology and the imaging features (with appropriate examples) of these complications and to propose a diagnostic algorithm based on MRI. Interpreting these scans in the light of clinical inputs very often helps the radiologist reach an appropriate diagnosis and help treatment and management

Acute leukemia classification by ensemble particle swarm model selection.

Science.gov (United States)

Escalante, Hugo Jair; Montes-y-Gómez, Manuel; González, Jesús A; Gómez-Gil, Pilar; Altamirano, Leopoldo; Reyes, Carlos A; Reta, Carolina; Rosales, Alejandro

2012-07-01

Acute leukemia is a malignant disease that affects a large proportion of the world population. Different types and subtypes of acute leukemia require different treatments. In order to assign the correct treatment, a physician must identify the leukemia type or subtype. Advanced and precise methods are available for identifying leukemia types, but they are very expensive and not available in most hospitals in developing countries. Thus, alternative methods have been proposed. An option explored in this paper is based on the morphological properties of bone marrow images, where features are extracted from medical images and standard machine learning techniques are used to build leukemia type classifiers. This paper studies the use of ensemble particle swarm model selection (EPSMS), which is an automated tool for the selection of classification models, in the context of acute leukemia classification. EPSMS is the application of particle swarm optimization to the exploration of the search space of ensembles that can be formed by heterogeneous classification models in a machine learning toolbox. EPSMS does not require prior domain knowledge and it is able to select highly accurate classification models without user intervention. Furthermore, specific models can be used for different classification tasks. We report experimental results for acute leukemia classification with real data and show that EPSMS outperformed the best results obtained using manually designed classifiers with the same data. The highest performance using EPSMS was of 97.68% for two-type classification problems and of 94.21% for more than two types problems. To the best of our knowledge, these are the best results reported for this data set. Compared with previous studies, these improvements were consistent among different type/subtype classification tasks, different features extracted from images, and different feature extraction regions. The performance improvements were statistically significant

Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

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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.

Cytosine Arabinoside Influx and Nucleoside Transport Sites in Acute Leukemia

OpenAIRE

Wiley, J. S.; Jones, S. P.; Sawyer, W. H.; Paterson, A. R. P.

1982-01-01

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells...

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

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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.

Future prospects of therapeutic clinical trials in acute myeloid leukemia

Science.gov (United States)

Khan, Maliha; Mansoor, Armaghan-e-Rehman; Kadia, Tapan M

2017-01-01

Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future. PMID:27771959

An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

Energy Technology Data Exchange (ETDEWEB)

Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

2002-12-01

A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Kato, Yasuhiro; Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji

2002-01-01

A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

Pericarditis as presenting manifestation of acute nonlymphocytic leukemia in a young child.

Science.gov (United States)

Chu, J Y; Demello, D; O'Connor, D M; Chen, S C; Gale, G B

1983-07-15

A case of acute nonlymphocytic leukemia presenting as pericarditis is reported in a five-year-old boy. Initially, a clinical diagnosis of viral pericarditis was made, because the child did not demonstrate hematologic or clinical manifestations of leukemia. Acute undifferentiated or lymphocytic leukemia. Acute undifferentiated or lymphocytic leukemia was diagnosed one week after admission when his peripheral blood count became abnormal. The patient did not respond to vincristine and prednisone. When cytochemical evaluation indicated acute myelomonocytic leukemia, employment of cytosine arabinoside and 6-thioguanine was instituted and the child began to improve. Currently, he is still in good remission and has no evidence of recurrence of pericarditis, 1 1/2 years after his initial presentation. In reviewing the literature, we found 17 patients who had leukemic pericardial effusion with cardiac tamponade. There are three reported cases of young children with pericardial effusion as the initial manifestation of acute lymphocytic leukemia, but no reported cases due to nonlymphocytic leukemia, as in this child.

Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives

Directory of Open Access Journals (Sweden)

McCulloch D

2017-03-01

Full Text Available Derek McCulloch, Christina Brown, Harry Iland Institute of Hematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia Abstract: Acute promyelocytic leukemia (APL is a distinct subtype of acute myeloid leukemia (AML with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms. Both are characterized by a balanced translocation between the long arms of chromosomes 15 and 17, [t(15;17(q24;q21], giving rise to a unique fusion gene PML-RARA and an abnormal chimeric transcription factor (PML-RARA, which disrupts normal myeloid differentiation programs. The success of current treatments for APL is in marked contrast to the vast majority of patients with non-promyelocytic AML. The overall prognosis in non-promyelocytic AML is poor, and although there has been an improvement in overall survival in patients aged <60 years, only 30%–40% of younger patients are still alive 5 years after diagnosis. APL therapy has diverged from standard AML therapy through the empirical discovery of two agents that directly target the molecular basis of the disease. The evolution of treatment over the last 4 decades to include all-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of patients in trials and rates of overall survival between 86% and 97%. Keywords: acute promyelocytic leukemia, ATRA, arsenic trioxide

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...

Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

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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.

The Prognostic Significance of The Serum Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL in Childhood Acute Leukemias

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Zeliha Haytoglu

2015-12-01

Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002. In patients with high-risk-grade (HRG of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008. In patients with common acute lymphoblastic leukemia antigen(CALLA(- B ALL compared with control group have shown low serum TRAIL levels in CALLA(- B ALL (p=0.004. Children with acute leukemias (ALL, AML who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004. Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL's role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed. [Cukurova Med J 2015; 40(4.000: 774-781

Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

Science.gov (United States)

Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

1980-01-01

The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

Data quality in the Danish National Acute Leukemia Registry

DEFF Research Database (Denmark)

Ostgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; 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....

Leukemia after therapy with alkylating agents for childhood cancer

International Nuclear Information System (INIS)

Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

1987-01-01

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

Childhood acute lymphoblastic leukemia: from genome to patient

International Nuclear Information System (INIS)

Kolenova, A.

2016-01-01

Acute lymphoblastic leukemia is the most common malignant disease in childhood. During recent decades prognosis for children with acute leukemia has greatly improved, including the patients treated in the Slovak Republic. The prognosis for these patients has improved as a result of the systematic and well-organized international research efforts and clinical trials. The advent of new genomic technologies has provided new insights into leukemogenesis, identified many novel subtypes of leukemia, and triggered development of new therapeutic formulations. The success of treatment depends on stratifying patients into risk group and incorporating novel treatment strategies.The Slovak pediatric leukemia group is actively incorporated into these international clinical trials and the outcome for our patients is comparable to the results published in Western Europe. (author)

Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer

International Nuclear Information System (INIS)

Wiggans, R.G.; Jacobson, R.J.; Fialkow, P.J.; Woolley, P.V. III; Macdonald, J.S.; Schein, P.S.

1978-01-01

A 64-yr-old female developed acute myeloblastic leukemia following radiation and drug therapy for colon carcinoma. The patient was heterozygous for glucose-6-phosphate dehydrogenase [G-6-PD) and displayed types A and B isoenzymes in nonhematopoietic tissue. In contrast, only type B G-6-PD was observed in peripheral blood white cells. In addition, a karyotypic abnormality was found in peripheral blood and marrow cells but not in skin fibroblasts. The data are consistent with a clonal origin of this leukemia

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...

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.

The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Taskinen, Mervi; Oskarsson, Trausti; Levinsen, Mette

2017-01-01

BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect...

Post-traumatic stress disorder symptoms in family caregivers of adult patients with acute leukemia from a dyadic perspective.

Science.gov (United States)

Jia, Mutian; Li, Jie; Chen, Chunyan; Cao, Fenglin

2015-12-01

Acute leukemia is a fatal disease in adults that not only affects the patients who suffer from it but also their family caregivers. No studies have investigated post-traumatic stress disorder symptoms (PTSS) in family caregivers of adult patients with acute leukemia using a matched sample. The current study examined PTSS in adult patients with acute leukemia and their family caregivers and investigated the factors associated with caregivers' PTSS. A total of 163 patient-caregiver dyads completed questionnaires assessing their PTSS, psychological resilience, and perceived social support. Hierarchical linear regression was used to explore the related factors of caregivers' PTSS. More caregivers than patients met caseness criteria for PTSS (36.8% vs. 18.4%, p caregivers, being more closely related to the patients (e.g., spouses and parents), having patients with higher PTSS and having lower psychological resilience were independently associated with more severe PTSS. Caregivers of acute leukemia patients had significantly more severe PTSS than did their patients. This study is the first to investigate PTSS among family caregivers of adult patients with acute leukemia and its related factors in a matched sample. More attention should be paid to the caregivers of patients with acute leukemia to minimize their PTSS and thus improve mental health of caregivers and reduce potential negative consequences for the patients themselves. Copyright © 2015 John Wiley & Sons, Ltd.

A vascular necrosis of bone. A complication of agressive therapy for acute lymphoblastic leukemia

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Vaidya, S.; Saika, S.; Sirohi, B.; Pai, S.; Advani, S. [Tata Memorial Hospital, Bombay (India). Dept. of Medical Oncology

1998-09-01

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and {sup 99m}technicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The medium period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awarness of this complication is important in order to have an early diagnosis so as to limit disability. (orig.)

A vascular necrosis of bone. A complication of agressive therapy for acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Vaidya, S.; Saika, S.; Sirohi, B.; Pai, S.; Advani, S.

1998-01-01

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99m technicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral he[. All h[ received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The medium period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awarness of this complication is important in order to have an early diagnosis so as to limit disability. (orig.)

A typical presentation of acute myeloid leukemia

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Udayakumar N

2006-01-01

Full Text Available A young man who presented with fever, altered sensorium and sudden onset tachypnea, is described. Arterial blood gas analysis, revealed the presence of severe high anion gap metabolic acidosis, with compensatory respiratory alkalosis and normal oxygen saturation. A detailed neurological, nephrological, biochemical and hematological evaluation, revealed the presence of Acute myeloid leukemia, with lactic acidosis and hyponatremia. There are very few reports of presentation of leukemia as lactic acidosis. This case report highlights the need for emergency room physicians, to consider the possibility of lactic acidosis, as one of the causes of high anion gap acidosis and to meticulously investigate the cause of lactic acidosis. We describe a rare clinical instance of lactic acidosis as the presenting manifestation of Acute myeloid leukemia.

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

International Nuclear Information System (INIS)

Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion

2005-01-01

Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RARα and PLZF-RARα fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RARα from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells

Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia

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Sinem Civriz Bozdag; Sinem Namdaroglu; Omur Kayikci; Gülsah Kaygusuz; Itir Demiriz; Murat Cinarsoy; Emre Tekgunduz; Fevzi Altuntas

2013-01-01

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.

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Schmidt, M; Hochhaus, A; König-Merediz, S A; Brendel, C; Proba, J; Hoppe, G J; Wittig, B; Ehninger, G; Hehlmann, R; Neubauer, A

2000-10-01

Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML. Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha. IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression. IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.

[Clinical and cytological differences in adult acute lymphatic and acute undifferentiated leukemia].

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Abbrederis, K; Schmalzl, F

1976-01-01

The usefulness for clinical purposes of the distinction of acute undifferentiated (AUL) and acute lymphocytic leukemia (ALL) is suggested by the following observations: 1. Maturation from AUL to ALL has not been observed. Transformation of ALL to AUL has been reported i.e. less of cytoplasmic polysaccharides; however this seems rather to be the effect of cytotoxic therapy and not a real change of the cytological type. 2. Significant differences among ALL and AUL can be noted as far as the therapeutic response is concerned: All of the 9 patients with ALL but only 2 out of 9 patients with AUL went into remission. The mean survival of the cases with ALL amounts to 34, that of AUL only to 4 months. Out of the patients with ALL 4 patients are still alive in persistant first remission after 77, 57, 36 and 28 months. 3. ALL occurs most frequently in young adults (mean age of 21 patients: 31.7 years): AUL is more frequent in elderly patients (Mean age of 18 patients: 57.6 years). 4. In our material ALL did never occur consequent to a typical preluekemic stage, which was followed either by myeloblastic, monocytic, erythroleukemic or undifferentiated leukemias.

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Science.gov (United States)

2015-06-03

Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature.

Science.gov (United States)

McIlwain, Laura; Sokol, Lubomir; Moscinski, Lynn C; Saba, Hussain I

2003-04-01

We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11 leukemia with lineage switch and extreme leukocytosis

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Čolović Nataša

2015-01-01

which may occur in patients with very high white blood cell count in addition with presence of a CD56 adhesion molecule and other concomitant thrombophilic factors. The treatment of AMI in patients with acute leukemias should include antiplatelet and anticoagulant therapy, even with more aggressive methods depending on patient’s age and clinical risk assessment. [Projekat Ministarstva nauke Republike Srbije, br. 41004

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.)

Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

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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.)

Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

DEFF Research Database (Denmark)

Jarden, Mary; Møller, Tom; Kjeldsen, Lars

2013-01-01

and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured...... and supervised counseling and exercise program.Methods/design: This paper presents the study protocol: Patient Activation through Counseling and Exercise -- Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction...... chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle...

Multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP and lung resistance protein (LRP gene expression in childhood acute lymphoblastic leukemia

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Elvis Terci Valera

Full Text Available CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP, and lung resistance protein (LRP may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR, and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005. The presence of the common acute lymphoblastic leukemia antigen (CALLA was correlated with increased LRP expression (p = 0.009 and increased risk of relapse or death (p = 0.05. The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05, as confirmed by multivariate analysis of the three genes studied (p = 0.035. DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the

Transfer of ERR for radiation-related leukemia from Japanese population to Chinese population

International Nuclear Information System (INIS)

Huang Liqiong; Sun Zhijuan; Zhao Yongcheng; Wang Jixian

2011-01-01

Objective: To establish a transfer model for excess relative risk (ERR) for radiation-related leukemia from Japanese population to Chinese population. Methods: Combined ERR of several subtypes of leukemia published in 1994, with the corresponding leukemia baseline incidence rates obtained from Cancer Incidence in Five Continents Vol. Ⅸ (CI5-Ⅸ) for Japanese population and Chinese population, a weighted risk transfer model was employed between an additive model and a multiplicative model, to execute ERR transfer. Results: A range of weighing factors was proposed for risk transfer models: weighing factor was 0.4 for male and 0.3 for female, acute lymphoblastic leukemia, acute myeloid leukemia and chronic myeloid leukemia. The uncertainty for ERR transfer was characterized by lognormal distribution. Conclusions: Based on the difference of baseline incidence rate for subtypes of leukemia between Japanese population and Chinese population, the transfer model and these weighing factors discussed in the present study could be applicable to transfer ERR for radiation-related leukemia from Japanese population to Chinese population. (authors)

Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

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Yong Ku

2011-11-01

Full Text Available Abstract Background To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. Case Presentation A 9 year-old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. Conclusion Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections.

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

The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

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Vali A Mehrzad

2012-01-01

Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

Prospective neurodevelopmental studies of two children treated with total body irradiation and bone marrow transplantation for acute leukemia in infancy

International Nuclear Information System (INIS)

Kaleita, T.; Tesler, A.; Feig, S.A.

1987-01-01

Five-year neurodevelopmental studies of two infants with acute leukemia are presented. Both patients underwent bone marrow transplantation (BMT) after conditioning with cyclophosphamide and total body irradiation (TBI). Neither patient was treated with intrathecal chemotherapy. Their outcome is remarkable for normal development of intelligence, language, perception, and motor coordination. These results suggest that TBI and BMT should be considered in future therapeutic studies of infants with acute leukemia, who are at great risk for failure of conventional therapy

Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature.

Science.gov (United States)

Naunheim, Matthew R; Nahed, Brian V; Walcott, Brian P; Kahle, Kristopher T; Soupir, Chad P; Cahill, Daniel P; Borges, Lawrence F

2010-09-01

Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH.

Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin.

Science.gov (United States)

Lavallée, Vincent-Philippe; Chagraoui, Jalila; MacRae, Tara; Marquis, Miriam; Bonnefoy, Arnaud; Krosl, Jana; Lemieux, Sébastien; Marinier, Anne; Pabst, Caroline; Rivard, Georges-Étienne; Hébert, Josée; Sauvageau, Guy

2018-02-23

Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor. Most intriguingly, the Podoplanin (PDPN) gene, involved in platelet aggregation, is aberrantly expressed in APL promyelocytes and is the most distinctive transcript for this disease. Using an antibody panel optimized for AML diagnosis by flow cytometry, we also found that PDPN was the most specific surface marker for APL, and that all-trans retinoic acid therapy rapidly decreases its expression. Functional studies showed that engineered overexpression of this gene in human leukemic cells causes aberrant platelet binding, activation and aggregation. PDPN-expressing primary APL cells, but not PDPN-negative primary leukemias, specifically induce platelet binding, activation and aggregation. Finally, PDPN expression on leukemia cells in a xenograft model was associated with thrombocytopenia and prolonged bleeding time in vivo. Together our results suggest that PDPN may contribute to the hemostatic perturbations found in APL.

Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

2011-01-01

illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

Aberrant Expression of CD19 and CD43 in a Patient With Therapy-Related Acute Myeloid Leukemia and a History of Mantle Cell Lymphoma

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Yen-Chuan Hsieh

2009-07-01

Full Text Available Mantle cell lymphoma (MCL is an aggressive B cell lymphoma with frequent involvement of the gastrointestinal tract and peripheral blood (PB. In addition to the B cell markers, the neoplastic cells express CD5 and CD43. In patients with a prior history of MCL with PB involvement, the appearance of leukemic cells after chemotherapy usually heralds a relapse, particularly if the leukemic cells express B cell markers and CD43. We report a patient with MCL who presented with multiple lymphomatous polyposis of the intestine. The staging procedures revealed the involvement of lymph nodes, bone marrow and PB. Three years after chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the PB was noted. Leukemic cells obtained from bone marrow aspirate expressed CD19 and CD43, suggesting a relapse. Detailed cytomorphological and immunophenotypic studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of therapy-related acute myeloid leukemia was made. This case illustrates the importance of morphologic examination and performing a complete antibody panel in the diagnosis of a suspected relapse in patients with a prior history of lymphoma.

Efficacy and Toxicity of Asparaginases During Prospective Drug Monitoring in Patients With Childhood Acute Lymphoblastic Leukemia

NARCIS (Netherlands)

W.H. Tong (Wing)

2014-01-01

markdownabstract__Abstract__ Intensified and effective asparaginase therapy is very important in modern treatment of childhood acute lymphoblastic leukemia. The use of native E.coli asparaginase in induction leads to a high rate of hypersensitivity reactions to PEGasparaginase in the

CAR-T therapy for leukemia: progress and challenges.

Science.gov (United States)

Wang, Xin; Xiao, Qing; Wang, Zhe; Feng, Wen-Li

2017-04-01

Despite the rapid development of therapeutic strategies, leukemia remains a type of difficult-to-treat hematopoietic malignancy that necessitates introduction of more effective treatment options to improve life expectancy and quality of patients. Genetic engineering in adoptively transferred T cells to express antigen-specific chimeric antigen receptors (CARs) has proved highly powerful and efficacious in inducing sustained responses in patients with refractory malignancies, as exemplified by the success of CD19-targeting CAR-T treatment in patients with relapsed acute lymphoblastic leukemia. Recent strategies, including manipulating intracellular activating domains and transducing viral vectors, have resulted in better designed and optimized CAR-T cells. This is further facilitated by the rapid identification of an accumulating number of potential leukemic antigens that may serve as therapeutic targets for CAR-T cells. This review will provide a comprehensive background and scrutinize recent important breakthrough studies on anti-leukemia CAR-T cells, with focus on recently identified antigens for CAR-T therapy design and approaches to overcome critical challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Slow-Stroke Back Massage on Symptom Cluster in Adult Patients With Acute Leukemia: Supportive Care in Cancer Nursing.

Science.gov (United States)

Miladinia, Mojtaba; Baraz, Shahram; Shariati, Abdolali; Malehi, Amal Saki

Patients with acute leukemia usually experience pain, fatigue, and sleep disorders, which affect their quality of life. Massage therapy, as a nondrug approach, can be useful in controlling such problems. However, very few studies have been conducted on the effects of massage therapy on the complications of leukemia. The aim of this study was to examine the effects of slow-stroke back massage (SSBM) on the symptom cluster in acute leukemia adult patients undergoing chemotherapy. In this randomized controlled trial, 60 patients with acute leukemia were allocated randomly to either the intervention or control group. The intervention group received SSBM 3 times a week (every other day for 10 minutes) for 4 weeks. The pain, fatigue, and sleep disorder intensities were measured using the numeric rating scale. The sleep quality was measured using the Pittsburgh Sleep Quality Index. Statistical tests of χ, t test, and the repeated-measure analysis of variance were used for data analysis. Results showed that the SSBM intervention significantly reduced the progressive sleep disorder, pain, fatigue, and improved sleep quality over time. Slow-stroke back massage, as a simple, noninvasive, and cost-effective approach, along with routine nursing care, can be used to improve the symptom cluster of pain, fatigue, and sleep disorders in leukemia patients. Oncology nurses can increase their knowledge regarding this symptom cluster and work to diminish the cluster components by using SSBM in adult leukemia patients.

Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse

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Elan Gorshein

2018-01-01

Full Text Available Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric population. It portends a poorer prognosis if present in adult patients. Although adults frequently achieve complete remission, relapse rates are substantial, particularly among the elderly and high-risk populations. In the absence of prophylactic intrathecal chemotherapy, more than half of patients may develop CNS involvement or relapse, which is associated with significant risk for systemic illness. This report describes a patient with acute lymphoblastic leukemia with repeated isolated CNS relapses. This case should remind clinicians that isolated CNS disease in the absence of systemic recurrence could successfully respond to intrathecal therapy and offer patients a favorable quality of life.

Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

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Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

2017-04-01

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

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Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

2016-02-01

Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations.

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Andersson, Anna; Olofsson, Tor; Lindgren, David; Nilsson, Björn; Ritz, Cecilia; Edén, Patrik; Lassen, Carin; Råde, Johan; Fontes, Magnus; Mörse, Helena; Heldrup, Jesper; Behrendtz, Mikael; Mitelman, Felix; Höglund, Mattias; Johansson, Bertil; Fioretos, Thoas

2005-12-27

Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)/PBX1, IGH@/MYC, ETV6(TEL)/RUNX1(AML1), 11q23/MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies.

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

ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CIRCULATING BLASTS PRESENTING AS SEVERE HYPERCALCEMIA

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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.

32P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

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Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

1978-01-01

In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi 32 P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32 P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32 P. The exposed population should be closely followed, since this will likely permit assessment of the risk of 32 P-induced leukemia in a nonneoplastic condition

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

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Göllner, Stefanie; Oellerich, Thomas; Agrawal-Singh, Shuchi

2017-01-01

In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction...

Cytogenetic patterns in acute nonlymphocytic leukemia

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Testa, J R; Rowley, J D

1978-01-01

Analysis of chromosomal banding patterns in acute nonlymphocytic leukemia (ANLL) reveals that approximately 50% of patients have an abnormal karyotype. Although there is substantial variability, certain nonrandom abnormalities occur, e.g., +8, -7, and the 8;21 translocation (often accompanied by loss of an X or Y chromosome). The 15;17 translocation appears to be highly specific for acute promyelocytic leukemia. These abnormalities usually are not seen in remission, but reappear in relapse, sometimes exhibiting further clonal evolution; a +8 is the most frequently observed evolutionary change. Patients with ANLL following treatment of a malignant lymphoma tend to have hypodiploid modal numbers and frequently show loss of a chromosome No. 5 or No. 7.

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

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Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

2015-01-01

Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

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Daniel Willian Lustosa de Sousa

2015-08-01

Full Text Available OBJECTIVE: To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment.METHODS: Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.RESULTS: The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%. The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5% than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/µL and white blood cell counts <5.0 Ã- 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%.CONCLUSION: The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age

HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.

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Scott, A A; Head, D R; Kopecky, K J; Appelbaum, F R; Theil, K S; Grever, M R; Chen, I M; Whittaker, M H; Griffith, B B; Licht, J D

1994-07-01

We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and

One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

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Thomas, E.D.; Buckner, C.D.; Banaji, M.

1977-01-01

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3 to 17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted rejected and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1--4 1 / 2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

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Ciprian Tomuleasa

2018-02-01

Full Text Available Chimeric antigen receptor (CAR T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

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Elisa Dorantes-Acosta

2012-01-01

Full Text Available Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide.

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Ishitsuka, Kenji; Shirahashi, Akihiko; Iwao, Yasuhiro; Shishime, Mikiko; Takamatsu, Yasushi; Takatsuka, Yoshifusa; Utsunomiya, Atae; Suzumiya, Junji; Hara, Syuji; Tamura, Kazuo

2004-04-01

Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

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Øyan, Anne Margrete; Ånensen, Nina; Bø, Trond Hellem; Stordrange, Laila; Jonassen, Inge; Bruserud, Øystein; Kalland, Karl-Henning; Gjertsen, Bjørn Tore

2009-01-01

The molecular changes in vivo in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response. The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting. Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells. Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex

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

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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...

Morbidity associated to the transfusion support in pediatric patients with acute leukemia in the National Cancer Institute

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Vizcaino Valderrama, Martha; Suarez Mattos, Amaranto; Hernandez Kunzel, Jorge Alberto; Restrepo, Alexandra

2002-01-01

Acute leukemia represents the most common cancer in pediatrics. The current treatments made necessary a hematological support which increases the risks of complications, like fever, immunologic reaction, infections and, graft versus host disease. The objective of the present study was to determine the morbidity associated with transfusion support in pediatric patients with acute leukemia. In the pediatric population with diagnosis of acute leukemia in the INC during one and half year, the morbidity associated with transfusions was low and couldn't be related to the treatment given to the transfused products

Therapeutic Effects of Myeloid Cell Leukemia-1 siRNA on Human Acute Myeloid Leukemia Cells

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Hadi Karami

2014-05-01

Full Text Available Purpose: Up-regulation of Mcl-1, a known anti-apoptotic protein, is associated with the survival and progression of various malignancies including leukemia. The aim of this study was to explore the effect of Mcl-1 small interference RNA (siRNA on the proliferation and apoptosis of HL-60 acute myeloid leukemia (AML cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative mRNA and protein expressions were quantified by quantitative real-time PCR and Western blotting, respectively. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of Mcl-1 siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using ELISA cell death assay. Results: Mcl-1 siRNA clearly lowered both Mcl-1 mRNA and protein levels in a time-dependent manner, leading to marked inhibition of cell survival and proliferation. Furthermore, Mcl-1 down-regulation significantly enhanced the extent of HL-60 apoptotic cells. Conclusion: Our results suggest that the down-regulation of Mcl-1 by siRNA can effectively trigger apoptosis and inhibit the proliferation of leukemic cells. Therefore, Mcl-1 siRNA may be a potent adjuvant in AML therapy.

Genital Infection as a First Sign of Acute Myeloid Leukemia

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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.

A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

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Xueqing Jiang

Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

Radiotherapy for leukemia in children, (1). Radiotherapy for central nervous system leukemia

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Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro [Maizuru National Hospital, Kyoto (Japan)

1983-07-01

Following the development of effective chemotherapy for producing remissions of acute lymphocytic leukemia (ALL), a new phenomenon has emerged in this disease--central nervous system (CNS) leukemia. CNS leukemia has become an increasingly frequent obstacle to prolongation of initial complete remission. Prophylactic irradiation of the CNS concomitant with intrathecal administration of methotrexate (IT-MTX) has proved to be effective in the reduction of CNS involvement. The purpose of this paper is to describe the results of irradiation for prevention of CNS leukemia and to discuss their implications. The patients consisted of 32 children with acute leukemia, admitted to MAIZURU National Hospital from 1966 to 1980; 22 patients of them had ALL, the others ANLL (acute non-lymphocytic leukemia). Preventive CNS therapy was started in 1974, (group A), but there was no prevention before 1974 (group B). 1. In group B, six patients was treated by therapeutic cranial irradiation, but all cases resulted in death. 2. In group A, seven patients was treated by prophylactic cranial irradiation combined with IT-MTX, and all of them have been alive without CNS relapse for 2 to 4 2/3 years after therapy. 3. In group A, none of 7 patients (0 %) relapsed CNS leukemia initially as compared to 7 (50 %) of 14 in group B, thus preventive efficacy was clear. 4. There were no severe complications attributable to the radiotherapy, with or without IT-MTX.

Evidence of a treatment dose response in acute nonlymphocytic leukemias which occur after therapy of non-Hodgkin's lymphoma

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Greene, M.H.; Young, R.C.; Merrill, J.M.; DeVita, V.T.

1983-01-01

We evaluated the occurrence of second cancers among 517 patients with non-Hodgkin's lymphoma (NHL) treated at the National Cancer Institute. Nine cases of acute nonlymphocytic leukemia (ANL) were observed compared to 0.08 cases expected (ratio of observed to expected cases, 105; 95% confidence limits, 48; 199). The excess risk of ANL was 4.1 cases per 1000 patients per year; the cumulative risk of ANL at 10 years was 7.9 +/- 3.2% (S.E.). A case-control study within the NHL cohort revealed that patients treated with both radiation and chemotherapy were at greater risk of ANL than were patients who received single-modality therapy (relative risk, 6.0; p less than 0.05), especially if the therapy included total-body or hemibody radiation. A positive correlation between cumulative radiation dose to the bone marrow and risk of ANL was demonstrated, independent of chemotherapy duration. A similar correlation between chemotherapy dose and risk of ANL was suggested but could not be proven with the available data. An apparent association between ANL risk and indolent NHL histological subtypes was due to the significantly larger amounts of potentially leukemogenic therapy to which these patients were repeatedly exposed. Only one case of ANL occurred among NHL patients whose initial therapy produced a durable complete remission. Our data are compatible with a multistep model of leukemogenesis and also underscore the need for curative NHL treatment regimens which minimize the duration and quantity of therapy required for optimum patient management

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

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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...... levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10(9) /l rise [1...

Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.

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Lin, Na; Fu, Wei; Zhao, Chen; Li, Bixin; Yan, Xiaojing; Li, Yan

2017-12-09

DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients. Four DNMT3A variants were identified, with DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines. Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls with non-malignant hematological disease, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in acute myeloid leukemia with different clinical association, and might play important roles in the pathophysiology of acute myeloid leukemia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Cytomorphology of acute mixed leukemia].

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Sucić, Mirna; Batinić, Drago; Zadro, Renata; Mrsić, Sanja; Labar, Boris

2008-10-01

Biphenotypic acute leukemias (AL) with blasts expressing both myeloid and lymphoid antigens are grouped with undifferentiated AL and bilineal AL in the group of AL of ambiguous lineage. Not all AL with myeloid and lymphoid antigens (ALMy+Ly) are true biphenotypic AL. According to EGIL scoring system, true biphenotypic ALMy+Ly are those with a sum of antigens 2 or more points for both myeloid and lymphoid lineage or for B and T lineage. The aim of this study was to compare cytomorphology and immunophenotype of AL to better understand the relation of certain AL morphology, immunophenotype, cytogenetics and molecular biology of biphenotypic AL. The study included a group of 169 AL patients treated from 1985 till 1991, and a group of 102 AL patients treated from 1993 till 1996 at Zagreb University Hospital Center. Bone marrow and peripheral blood of the two groups of AL patients were analyzed according to Pappenheim (May-Grunwald-Giemsa), cytochemical and alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunocytochemical staining. Flow cytometry immunophenotyping of bone marrow was also done in both patient groups. In the group of 169 adult AL patients, 116 were cytomorphologically classified as acute myeloblastic leukemias (AML), 35 as acute lymphoblastic leukemias (ALL) and 18 as acute undifferentiated leukemias (ANLM). In 6 (3.4%) of 169 AL patients, blasts expressed both myeloid and lymphoid antigens. In the group of 102 AL patients there were 19 (18.6%) ALMy+Ly. In 64 patients cytomorphologically classified into AML subgroup out of 102 AL patients, there were 15 (14.7%/102; 23.4%/64) AML with lymphoid antigens (AMLLy+). In 35 patients cytomorphologically diagnosed as ALL and 3 as ANLM out of 102 AL, there were 4 (3.9%/102; 10.5%/38) ALL with myeloid antigens (ALLMy+). The incidence of mixed AL in 102 AL was more consistent with other studies, pointing to the necessity of myeloperoxidase (MPO), CD7 and TdT determination as part of standard immunophenotyping

ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia

OpenAIRE

Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Krajinovic, Maja

2011-01-01

Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these gene...

Azacitidine and lenalidomide as an alternative treatment for refractory acute myeloid leukemia: a case report.

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Todaro, Juliana; Bollmann, Patrícia Weinschenker; Rother, Edna Terezinha; del Giglio, Auro

2015-01-01

Refractory acute myeloid leukemia (AML) is a difficult disease to control with second or third-line chemotherapy regimens. In this report, we describe using azacitidine in combination with lenalidomide as salvage therapy. 52-year-old female was diagnosed with refractory AML and high-risk cytogenetics: complex monosomal karyotype consisting of t (3, 3) in association with monosomy 7 and del 5q. Morphological remission associated with maintenance of the cytogenetic abnormality of chromosome 3 and disappearance of the abnormalities relating to chromosomes 5 and 7 was achieved after three cycles of combination therapy with azacitidine and lenalidomide. Azacitidine plus lenalidomide can be a therapeutic option for patients with refractory AML, as illustrated in this case.

Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

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2018-05-24

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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 in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Secondary Acute Myeloid Leukemia

Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

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Pei-Jie Shi

2016-02-01

Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK down-regulation in the treatment of ALL. Methods The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID mouse model. Results When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2 gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. Conclusions FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel

Patients' Adherence in the Maintenance Therapy of Children and Adolescents with Acute Lymphoblastic Leukemia.

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Kremeike, K; Juergens, C; Alz, H; Reinhardt, D

2015-11-01

Acute lymphoblastic leukemia (ALL) is the most common form of paediatric cancer. Maintenance therapy as last treatment phase includes oral chemotherapy with methotrexate (MTX) and mercaptopurine (6-MP), self- or parent-administered at home, given for about 1 ½ years, and qualified as decisive for an optimum therapy outcome. The aim of our study was to analyze factors influencing the adherence of patients with ALL undergoing maintenance therapy and their families. A multi-method study was undertaken between 11/2011 and 10/2014 with patients surveyed by the Hannover Medical School outpatient clinic, including a questionnaire survey and qualitative interviews with parents as well as blood samples of the patients. 33 questionnaires, 27 interviews and blood samples of 26 patients could be analyzed. Only one third of the blood samples showed concentrations of the 6-MP active metabolite within the therapeutic reference range. Parents named the clinical doctor as their main advisor on medication intake. 36% (12/33) of the participants stated that medication intake has not always occurred the way medication was prescribed. Drug formulation and drug intake information could be identified as determinants of adherence. Parents' problems to obtain information are partly caused by different study results concerning the correct timing of the drug intake and drug interactions with milk products. Parents' information on drug therapy should be more consistent and the pharmaceutical formulations have to be adapted to patients' needs to improve adherence and thereby the chance of long-term remission. © Georg Thieme Verlag KG Stuttgart · New York.

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

Science.gov (United States)

2018-05-14

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Clinical relevance of IDH1/2 mutant allele burden during follow-up in acute myeloid leukemia. A study by the French ALFA group

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Ferret, Yann; Boissel, Nicolas; Helevaut, Nathalie; Madic, Jordan; Nibourel, Olivier; Marceau-Renaut, Alice; Bucci, Maxime; Geffroy, Sandrine; Celli-Lebras, Karine; Castaigne, Sylvie; Thomas, Xavier; Terré, Christine; Dombret, Hervé; Preudhomme, Claude; Renneville, Aline

2018-01-01

Assessment of minimal residual disease has emerged as a powerful prognostic factor in acute myeloid leukemia. In this study, we investigated the potential of IDH1/2 mutations as targets for minimal residual disease assessment in acute myeloid leukemia, since these mutations collectively occur in 15–20% of cases of acute myeloid leukemia and now represent druggable targets. We employed droplet digital polymerase chain reaction assays to quantify IDH1R132, IDH2R140, and IDH2R172 mutations on genomic DNA in 322 samples from 103 adult patients with primary IDH1/2 mutant acute myeloid leukemia and enrolled on Acute Leukemia French Association (ALFA) - 0701 or -0702 clinical trials. The median IDH1/2 mutant allele fraction in bone marrow samples was 42.3% (range, 8.2 – 49.9%) at diagnosis of acute myeloid leukemia, and below the detection limit of 0.2% (range, <0.2 – 39.3%) in complete remission after induction therapy. In univariate analysis, the presence of a normal karyotype, a NPM1 mutation, and an IDH1/2 mutant allele fraction <0.2% in bone marrow after induction therapy were statistically significant predictors of longer disease-free survival. In multivariate analysis, these three variables remained significantly predictive of disease-free survival. In 7/103 (7%) patients, IDH1/2 mutations persisted at high levels in complete remission, consistent with the presence of an IDH1/2 mutation in pre-leukemic hematopoietic stem cells. Five out of these seven patients subsequently relapsed or progressed toward myelodysplastic syndrome, suggesting that patients carrying the IDH1/2 mutation in a pre-leukemic clone may be at high risk of hematologic evolution. PMID:29472349

Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

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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.

Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

NARCIS (Netherlands)

Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

2009-01-01

Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant

Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia | Office of Cancer Genomics

Science.gov (United States)

NCI's TARGET Initiative reported the discovery of a novel genetic marker for children with acute lymphoblastic leukemia (ALL) in the January 7, 2009, advance online edition of The New England Journal of Medicine. The genetic alteration identified, IKZF1, should improve clinicians' ability to identify high-risk patients and better assign these patients to appropriate therapy.

Allogeneic stem cell transplantation in acute myeloid leukemia

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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%.

The impact of cranial irradiation on the growth of children with acute lymphocytic leukemia

International Nuclear Information System (INIS)

Wells, R.J.; Foster, M.B.; D'Ercole, A.J.; McMillan, C.W.

1983-01-01

Heights, height velocities, weights, and weight velocities were measured serially in 21 patients with acute lymphocytic leukemia (ALL) who had survived three to five years in continuous complete remission. These patients were assigned randomly to treatment regimens that varied according to whether cranial irradiation was used. Patients receiving cranial irradiation had lower height velocities during therapy than normal subjects and patients not receiving cranial irradiation. Twenty-two other children with ALL, who were irradiated but not randomized, exhibited similar alterations in growth. These results indicate that cranial irradiation, and not leukemia or antileukemia chemotherapy, causes reduced growth

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Schmiegelow, K; Forestier, E; Hellebostad, M

2010-01-01

Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors...

Leucemia congénita aguda Acute congenital leukemia

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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.

Acute lymphoblastic leukemia mimicking Wilms tumor at presentation.

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Singh, Amitabh; Mandal, Anirban; Guru, Vijay; Seth, Rachna

2016-09-01

Acute lymphoblastic leukemia (ALL), the commonest malignancy of childhood, is known to manifest with a myriad of atypical presentations. Nephromegaly is a rare presentation of childhood ALL with hepatic mass being even rarer. We present a 3 year-old child with unilateral renal mass and hepatic mass lesion with normal blood counts, initially suspected to have metastatic Wilms tumor based on clinical, radiological and WT1 positivity on immunocytochemistry of renal mass. He was later diagnosed as ALL with peripheral blood flowcytometry and bone marrow examination. Renomegaly at presentation of acute leukemia is not necessarily due to leukemic infiltration and rarely leads to renal impairment. The radiological differential of such a renal mass includes both benign and malignant entities including metastasis. Over-expression of WT1 mRNA has been found in a number of solid tumors and hematological malignancies and is far from being diagnostic of Wilms tumor. Again, a small number of children with acute leukemia may have a deceptively normal complete blood count at presentation. Though, initial all (clinical, radiological, hematological, and immunocytological) parameters pointed towards a diagnosis of Wilms tumor in our case, the subsequent development of thrombocytopenia and lymphocytic leukocytosis prompted further investigation and final diagnosis of ALL. WT1 positivity is a known phenomenon in childhood ALL and undifferentiated lymphoblasts may be positive for WT1 and negative for Leucocyte common antigen. Acute leukemia with renal and hepatic mass with normal blood counts at presentation is a diagnostic challenge.

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

Plasminogen activator inhibitor-2 in patients with monocytic leukemia.

Science.gov (United States)

Scherrer, A; Kruithof, E K; Grob, J P

1991-06-01

Plasma and tumor cells from 103 patients with leukemia or lymphoma at initial presentation were investigated for the presence of plasminogen activator inhibitor-2 (PAI-2) antigen, a potent inhibitor of urokinase. PAI-2 was detected in plasma and leukemic cells of the 21 patients with leukemia having a monocytic component [acute myelomonocytic (M4), acute monoblastic (M5), and chronic myelomonocytic leukemias], and in the three patients with acute undifferentiated myeloblastic leukemia (M0). In contrast, this serine protease inhibitor was undetectable in 79 patients with other subtypes of acute myeloid leukemia or other hematological malignancies. Serial serum PAI-2 determinations in 16 patients with acute leukemia at presentation, during therapy, remission, and relapse revealed that in the five patients with M4-M5, elevated PAI-2 levels rapidly normalized under therapy and during remission, but increased again in the patients with a relapse associated with an M4-M5 phenotype. Thus, PAI-2 seems to be a marker highly specific for the active stages of monocytic leukemia, i.e. presentation and relapse. The presence of PAI-2 in the plasma and cells of patients with M0 may give a clue to a monocytic origin of these cells.

Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report

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Zarallo Luis

2007-05-01

Full Text Available Abstract Background Fusarium spp. is being isolated with increasing frequency as a pathogen in oncohematologic patients. Caspofungin and amphotericin B have been reported to have synergistic activity against Fusarium spp. Case presentation We herein report a case of disseminated fusariosis diagnosed by chest CT scan and positive blood cultures to Fusarium spp. Because the patient's clinical condition deteriorated, CRP levels increased, and blood cultures continued to yield Fusarium spp. despite liposomal amphotericin B monotherapy up to 5 mg/kg daily, treatment with caspofungin was added. Within 2 weeks of onset of combined antifungal therapy, the chest CT scan demonstrated a progressive resolution of the pulmonary lesions. Upon discontinuation of intravenous antifungals, the patient received suppressive therapy with oral voriconazole. Three months later, a chest CT scan showed no abnormalities. Twenty-five months after discontinuation of all antifungal therapy, the patient remains in complete remission of her neoplastic disease with no signs of clinical activity of the Fusarium infection. Conclusion This is the first description of successful treatment of disseminated fusariosis in a pediatric patient with acute lymphoblastic leukemia with caspofungin and amphotericin B followed by oral suppressive therapy with voriconazole.

Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

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Kamran Kaveh

2017-07-01

Full Text Available Philadelphia chromosome-positive (Ph+ acute lymphoblastic leukemia (ALL is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR in combination with TKI therapy overcome chemo-resistance. Additionally, we developed a mathematical model, parameterized by cell viability experiments under Nilotinib treatment and LDR, to explain the cellular response to combination therapy. The addition of LDR significantly reduced drug resistance both in vitro and in computational model. Decreased expression level of phosphorylated AKT suggests that the combination treatment plays an important role in overcoming resistance through the AKT pathway. Model-predicted cellular responses to the combined therapy provide good agreement with experimental results. Augmentation of LDR and Nilotinib therapy seems to be beneficial to control Ph+ leukemia resistance and the quantitative model can determine optimal dosing schedule to enhance the effectiveness of the combination therapy.

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

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Xenofon Papanikolaou

2011-10-01

Full Text Available Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

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Bart Barlogie

2011-01-01

Full Text Available

Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

Science.gov (United States)

Dayton, Vanessa J; McKenna, Robert W; Yohe, Sophia L; Dolan, Michelle M; Courville, Elizabeth; Alvarez, Harold; Linden, Michael A

2017-01-01

Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Recent advances in the management of pediatric acute lymphoblastic leukemia [version 1; referees: 2 approved

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Jan Starý

2016-11-01

Full Text Available Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood. Despite enormous improvement of prognosis during the last half century, ALL remains a major cause of childhood cancer-related mortality. During the past decade, whole genomic methods have enhanced our knowledge of disease biology. Stratification of therapy according to early treatment response measured by minimal residual disease allows risk group assignment into different treatment arms, ranging from reduction to intensification of treatment. Progress has been achieved in academic clinical trials by optimization of combined chemotherapy, which continues to be the mainstay of contemporary treatment. The availability of suitable volunteer main histocompatibility antigen-matched unrelated donors has increased the rates of hematopoietic stem cell transplantation (HSCT over the past two decades. Allogeneic HSCT has become an alternative treatment for selected, very-high-risk patients. However, intensive treatment burdens children with severe acute toxic effects that can cause permanent organ damage and even toxic death. Immunotherapeutic approaches have recently come to the forefront in ALL therapy. Monoclonal antibodies blinatumomab and inotuzumab ozogamicin as well as gene-modified T cells directed to specific target antigens have shown efficacy against resistant/relapsed leukemia in phase I/II studies. Integration of these newer modalities into combined regimens with chemotherapy may rescue a subset of children not curable by contemporary therapy. Another major challenge will be to incorporate less toxic regimens into the therapy of patients with low-risk disease who have a nearly 100% chance of being cured, and the ultimate goal is to improve their quality of life while maintaining a high cure rate.

Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

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Hurley, M Yadira; Ghahramani, Grant K; Frisch, Stephanie; Armbrecht, Eric S; Lind, Anne C; Nguyen, Tudung T; Hassan, Anjum; Kreisel, Friederike H; Frater, John L

2013-05-01

We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

Children's Oncology Group's 2013 blueprint for research: acute myeloid leukemia.

Science.gov (United States)

Gamis, Alan S; Alonzo, Todd A; Perentesis, John P; Meshinchi, Soheil

2013-06-01

For the 365 children diagnosed with acute myeloid leukemia in the US annually, 5-year survival for patients on COG trials with low, intermediate, and high risk disease is 83%, 62%, and 23%, respectively. Recent advances include improved therapeutic stratification, improved survival with dose intensification, and further elucidation of the heterogeneity specific to childhood AML. These discoveries now guide current strategy incorporating targeted agents to pathways specific to childhood AML as well as evaluating methods to increase the sensitivity of the leukemic stem cell, first in Phase II feasibility trials followed by Phase III efficacy trials of the most promising agents. Acute myeloid leukemia in children, though with similar subgroups to adults, remains uniquely different based upon quite different prevalence of subtypes as well as overall response to therapy. The Children's Oncology Group's research agenda builds upon earlier efforts to better elucidate the leukemogenic steps distinct to childhood AML in order to more scientifically develop and test novel therapeutic approaches to the treatment and ultimate cure for children with this disorder. Pediatr Blood Cancer 2013; 60: 964-971. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic)

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Ishii, Kazusa; Barrett, Austin J.

2016-01-01

There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID:26834952

Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia

International Nuclear Information System (INIS)

Kaiser, M; Kühnl, A; Reins, J; Fischer, S; Ortiz-Tanchez, J; Schlee, C; Mochmann, L H; Heesch, S; Benlasfer, O; Hofmann, W-K; Thiel, E; Baldus, C D

2011-01-01

Heat shock protein (HSP) 70 is aberrantly expressed in different malignancies and has emerged as a promising new target for anticancer therapy. Here, we analyzed the in vitro antileukemic effects of pifithrin-μ (PFT-μ), an inhibitor of inducible HSP70, in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cell lines, as well as in primary AML blasts. PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μ, and was highly active in primary AML blasts with a median IC50 of 8.9 μ (range 5.7–37.2). Importantly, higher IC50 values were seen in normal hematopoietic cells. In AML and ALL, PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent fashion. PFT-μ also led to an increase of the active form of caspase-3 and reduced the intracellular concentrations of AKT and ERK1/2 in NALM-6 cells. Moreover, PFT-μ enhanced cytotoxicity of cytarabine, 17-(allylamino)-17-desmethoxygeldanamycin, suberoylanilide hydroxamic acid, and sorafenib in NALM-6, TOM-1 and KG-1a cells. This is the first study demonstrating significant antileukemic effects of the HSP70 inhibitor PFT-μ, alone and in combination with different antineoplastic drugs in both AML and ALL. Our results suggest a potential therapeutic role for PFT-μ in acute leukemias

TBI parameters and relapse of acute leukemia

International Nuclear Information System (INIS)

Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

1994-01-01

The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

[Ultrastructure and Raman Spectral Characteristics of Two Kinds of Acute Myeloid Leukemia Cells].

Science.gov (United States)

Liang, Hao-Yue; Cheng, Xue-Lian; Dong, Shu-Xu; Zhao, Shi-Xuan; Wang, Ying; Ru, Yong-Xin

2018-02-01

To investigate the Raman spectral characteristics of leukemia cells from 4 patients with acute promyelocytic leukemia (M 3 ) and 3 patients with acute monoblastic leukemia (M 5 ), establish a novel Raman label-free method to distinguish 2 kinds of acute myeloid leukemia cells so as to provide basis for clinical research. Leukemia cells were collected from bone marrow of above-mentioned patients. Raman spectra were acquired by Horiba Xplora Raman spectrometer and Raman spectra of 30-50 cells from each patient were recorded. The diagnostic model was established according to principle component analysis (PCA), discriminant function analysis (DFA) and cluster analysis, and the spectra of leukemia cells from 7 patients were analyzed and classified. Characteristics of Raman spectra were analyzed combining with ultrastructure of leukemia cells. There were significant differences between Raman spectra of 2 kinds of leukemia cells. Compared with acute monoblastic leukemia cells, the spectra of acute promyelocytic leukemia cells showed stronger peaks in 622, 643, 757, 852, 1003, 1033, 1117, 1157, 1173, 1208, 1340, 1551, 1581 cm -1 . The diagnostic models established by PCA-DFA and cluster analysis could successfully classify these Raman spectra of different samples with a high accuracy of 100% (233/233). The model was evaluated by "Leave-one-out" cross-validation and reached a high accuracy of 97% (226/233). The level of macromolecules of M 3 cells is higher than that of M 5 . The diagnostic models established by PCA-DFA can classify these Raman spectra of different cells with a high accuracy. Raman spectra shows consistent result with ultrastructure by TEM.

A case of acute lymphoblastic leukemia with an intracerebellar mass

International Nuclear Information System (INIS)

Oshima, Yukio; Shitara, Toshiji; Kuribayashi, Toshio; Noji, Takashi; Kuroume, Takayoshi

1983-01-01

A 3-year-old boy, who had a complaint of hemorrhagic diathesis, was diagnosed as having acute lymphoblastic leukemia. Remission was induced by a combination of vincristine and prednisolone. Prophylactic intrathecal methotrexate and cranial irradiation were administered. Two years later, he was hospitalized for CNS leukemia and treated with multiple doses of intrathecal methotrexate. At the time, the results of CT scanning were normal. Six months later, though, he developed vomiting and lethargy. CT scanning showed a mass of an increased density in the right cerebellar hemisphere that displaced the fourth ventricle to the left and resulted in an obstructive hydrocephalus. Decompression was done by means of Ommaya reservoir setting. Soon his consciousness returned to normal, and CT scanning revealed no abnormal mass three weeks later. A month later, though, the CNS leukemia returned. He developed vomiting and a headache, and CT scanning showed a high-density mass in the right cerebellar hemisphere. The mass was diagnosed as hematoma. He died one month later. In this case, the previous mass showed evidence of a relatively uniform contrast enhancement, which is consistent with the intracerebral leukemic mass reported by Wendling. In Japan, this is the first report of an intracerebellar mass of acute lymphoblastic leukemia as perceived by CT scanning. (author)

Comparison of health-related quality of life of children during maintenance therapy with acute lymphoblastic leukemia versus siblings and healthy children in India.

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Bansal, Minakshi; Sharma, Kamlesh K; Vatsa, Manju; Bakhshi, Sameer

2013-05-01

Data on quality of life (QOL) specifically in maintenance therapy of acute lymphoblastic leukemia (ALL) are minimal. This study was done to assess various items listed in domains of QOL (physical, emotional, social and school health domains) of children with ALL during maintenance therapy, and compare the same with those of their siblings and other healthy children. Forty children on maintenance therapy of ALL, 40 siblings and 40 healthy children were assessed for QOL by child self-report using PedsQL 4.0 Generic Core in the local language. Means were computed and compared for each domain with one-way analysis of variance (ANOVA), wherein higher values reflected better QOL. Overall QOL of children with ALL in maintenance therapy (77.16 ± 10.98) was significantly poorer than that of siblings (93.56 ± 4.41) and healthy children (93.02 ± 3.76) (p fear, anger, sleeping problems) among children with ALL. In the social health domain, children with ALL reported difficulty in maintaining friendships and competing. QOL of siblings was as good as that of healthy children in physical, social and school health domains, but they had increased emotional problems such as anger and sadness. Healthy children reported significantly higher future worries and bullying than children with ALL and siblings. This study validated that the QOL of children with ALL during maintenance therapy was significantly poorer than that of siblings and healthy children. The study identified various items in each domain of QOL that were affected in these children, and thus would assist in guiding healthcare professionals to focus on these specific items so as to improve their overall QOL.

Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

International Nuclear Information System (INIS)

Tanaka, K.; Tanaka, H.; Kamada, N.

2003-01-01

It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

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Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

2016-06-01

Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently

Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid Leukemia.

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Elmariah, Hany; Pratz, Keith W

2017-07-01

Adult acute myeloid leukemia (AML) is often associated with a poor prognosis, with allogeneic transplantation representing the greatest chance of cure for eligible patients. Historically, the preferred donor source is a human leukocyte antigen-matched blood relative, although only approximately 30% of patients have access to such a donor. Alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical related donors, are available for almost every patient and are increasingly being used for patients without a matched related donor. Survival outcomes with these alternative donor sources now approximate those of matched related donor transplants. Given the safety and success of alternative donor transplants, comparative trials are needed to reassess the optimal donor source for patients with AML. This review summarizes the available data on these alternative donor transplants. Further investigation is needed to contemporize donor selection algorithms, but, in the current era, donor availability should no longer preclude a patient's eligibility for an allogeneic blood or marrow transplant. Copyright © 2017 by the National Comprehensive Cancer Network.

The Stoplight Program: A Proactive Physical Therapy Intervention for Children With Acute Lymphoblastic Leukemia.

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Tanner, Lynn; Sencer, Susan; Hooke, Mary C

Chemotherapy may cause neuromuscular impairments that can have life-long effects. The Stoplight Program (SLP) was developed as a proactive physical therapy (PT) intervention directed at impairments in children with acute lymphoblastic leukemia (ALL). In this program evaluation, we assessed the feasibility of the SLP delivered as part of standard care and identified body function and activity patterns in patients who received the intervention. Children ages 1 to 22 years, diagnosed with ALL, received an assessment by a physical therapist as part of usual care. The SLP intervention used 3 levels to categorize the impairment levels and intensity of PT. Of the children (n = 135) screened, 46% completed 5 intervention visits and 32% completed the program and met discharge criteria. At initial assessment, 46% of children ages 1 to 5 years and 67% of children ages 6 to 22 years had abnormal motor function. Those completing the program tested within the healthy norms. Research is needed on variables that influence adherence to a PT program and the range of functional impairment and activity limitations in this population.

Treatment-related Myelodysplastic Syndrome in a Child With Acute Myeloid Leukemia and TPMT Heterozygosity

DEFF Research Database (Denmark)

Stensman, Lars M; Kjeldsen, Eigil; Nersting, Jacob

2015-01-01

INTRODUCTION: We describe a patient diagnosed with acute myeloid leukemia (AML) and low activity of thiopurine methyltransferase (TPMT) who developed secondary myelodysplastic syndrome after treatment. OBSERVATION: A 10-year-old boy presented with AML-M2 with t(8;21)(q22;q22) and genotyping...

CD22: A Promising Target for Acute Lymphoblastic Leukemia Treatment | Center for Cancer Research

Science.gov (United States)

There are about 4,000 new cases of acute lymphoblastic leukemia (ALL) in the United States each year. Great improvements have been made in the treatment of ALL, but many patients suffer from side effects of standard therapy and continue to die of this disease. One of the most promising therapeutic strategies includes engineering T cells with a chimeric antigen receptor (CAR)

Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features

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Schwab, Claire J.; Chilton, Lucy; Morrison, Heather; Jones, Lisa; Al-Shehhi, Halima; Erhorn, Amy; Russell, Lisa J.; Moorman, Anthony V.; Harrison, Christine J.

2013-01-01

In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute lymphoblastic leukemia and the recently reported copy number abnormalities affecting significant leukemia associated genes. In a consecutive series of 1427 childhood B-cell precursor acute lymphoblastic leukemia patients, we have determined the incidence and type of copy number abnormalities using multiplex ligation-dependent probe amplification. We have shown strong links between certain deletions and cytogenetic subtypes, including the novel association between RB1 deletions and intrachromosomal amplification of chromosome 21. In this study, we characterized the different copy number abnormalities and show heterogeneity of PAX5 and IKZF1 deletions and the recurrent nature of RB1 deletions. Whole gene losses are often indicative of larger deletions, visible by conventional cytogenetics. An increased number of copy number abnormalities is associated with NCI high risk, specifically deletions of IKZF1 and CDKN2A/B, which occur more frequently among these patients. IKZF1 deletions and rearrangements of CRLF2 among patients with undefined karyotypes may point to the poor risk BCR-ABL1-like group. In conclusion, this study has demonstrated in a large representative cohort of children with B-cell precursor acute lymphoblastic leukemia that the pattern of copy number abnormalities is highly variable according to the primary genetic abnormality. PMID:23508010

Azacitidine and lenalidomide as an alternative treatment for refractory acute myeloid leukemia: a case report

Directory of Open Access Journals (Sweden)

Juliana Todaro

Full Text Available CONTEXT:Refractory acute myeloid leukemia (AML is a difficult disease to control with second or third-line chemotherapy regimens. In this report, we describe using azacitidine in combination with lenalidomide as salvage therapy.CASE REPORT:52-year-old female was diagnosed with refractory AML and high-risk cytogenetics: complex monosomal karyotype consisting of t (3, 3 in association with monosomy 7 and del 5q. Morphological remission associated with maintenance of the cytogenetic abnormality of chromosome 3 and disappearance of the abnormalities relating to chromosomes 5 and 7 was achieved after three cycles of combination therapy with azacitidine and lenalidomide.CONCLUSION:Azacitidine plus lenalidomide can be a therapeutic option for patients with refractory AML, as illustrated in this case.

[Cellular immunophenotypes in 97 adults with acute leukemia].

Science.gov (United States)

Piedras, J; López-Karpovitch, X; Cárdenas, M R

1997-01-01

To analyze hematopoietic cell surface antigen reactivity in acute leukemia (AL) by flow cytometry and identify acute mixed-lineage leukemias (AMLL) employing the most widely accepted criteria. Ninety seven patients with de novo AL were studied. Cell surface antigens were investigated with monoclonal antibodies directed to: B lymphoid (CD10, CD19, CD20, CD21, CD22); T lymphoid (CD2, CD3, CD5, CD7); and myeloid (CD13, CD14, CD15, CD33, CD41) cell lineages. Maturation cell-associated antigens (CD34, HLA-DR and TdT) were also studied. Twelve patients unclassified by cytomorphology could be classified by immunophenotype. Using cytomorphologic, cytochemical and immunophenotypic data, 54 cases corresponded to acute lymphoblastic leukemia (ALL) and 43 were acute myeloblastic leukemia (AML). In All there were 63% B lineage, 15% T, 7% T/B, 6% undifferentiated and 9% mixed-lineage (coexpression of two or more myeloid-associated antigens). In AML, myeloid immunophenotype was observed in 86% undifferentiated in 2%, and mixed-lineage in 12% (coexpression of two or more lymphoid-associated antigens). In addition, 26% of ALL cases and 12% of AML cases expressed a single myeloid and lymphoid antigen respectively. The most common aberrant antigens in ALL and AML were CD13 and CD7 respectively. The highest frequency of CD34 antigen expression (90%) was detected in patients with AMLL. Flow cytometric immunophenotypic analysis allowed to: a) establish diagnosis in cytomorphologically unclassified cases; b) identify AMLL with a frequency similar to that reported in other series; and c) confirm the heterogeneity of AL.

CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in Ras pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response.

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Dixon, Zach A; Nicholson, Lindsay; Zeppetzauer, Martin; Matheson, Elizabeth; Sinclair, Paul; Harrison, Christine J; Irving, Julie A E

2017-04-01

Relapsed acute lymphoblastic leukemia is the most common cause of cancer-related mortality in young people and new therapeutic strategies are needed to improve outcome. Recent studies have shown that heterozygous inactivating mutations in the histone acetyl transferase, CREBBP , are particularly frequent in relapsed childhood acute lymphoblastic leukemia and associated with a hyperdiploid karyotype and KRAS mutations. To study the functional impact of CREBBP haploinsufficiency in acute lymphoblastic leukemia, RNA interference was used to knock down expression of CREBBP in acute lymphoblastic leukemia cell lines and various primagraft acute lymphoblastic leukemia cells. We demonstrate that attenuation of CREBBP results in reduced acetylation of histone 3 lysine 18, but has no significant impact on cAMP-dependent target gene expression. Impaired induction of glucocorticoid receptor targets was only seen in 1 of 4 CREBBP knockdown models, and there was no significant difference in glucocorticoid-induced apoptosis, sensitivity to other acute lymphoblastic leukemia chemotherapeutics or histone deacetylase inhibitors. Importantly, we show that CREBBP directly acetylates KRAS and that CREBBP knockdown enhances signaling of the RAS/RAF/MEK/ERK pathway in Ras pathway mutated acute lymphoblastic leukemia cells, which are still sensitive to MEK inhibitors. Thus, CREBBP mutations might assist in enhancing oncogenic RAS signaling in acute lymphoblastic leukemia but do not alter response to MEK inhibitors. Copyright© Ferrata Storti Foundation.

Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis.

Science.gov (United States)

Shah, Harsh; Bradford, Carol; Sayar, Hamid

2015-01-01

We report a case of acute promyelocytic leukemia (APL) presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA-) containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia.

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Ponciano-Gómez, Alberto; Martínez-Tovar, Adolfo; Vela-Ojeda, Jorge; Olarte-Carrillo, Irma; Centeno-Cruz, Federico; Garrido, Efraín

2017-10-01

Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real-time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis

Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: a population based case-control study.

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Liu, Chen-Yu; Hsu, Yi-Hsiang; Wu, Ming-Tsang; Pan, Pi-Chen; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C

2009-01-13

Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia. A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses. Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15-2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37-0.83) and bean-curd (OR = 0.55; 95% CI: 0.34-0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea. Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.

Considerations in the design of clinical trials for pediatric acute lymphoblastic leukemia

OpenAIRE

Devidas, Meenakshi; Anderson, James R

2013-01-01

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although outcomes for children with ALL have improved dramatically over the last 50 years, ALL remains the leading cause of childhood cancer death. In addition, high-risk patient subsets can be identified with significantly inferior survival. In the current era of therapies directed at specific molecular targets, the use of conventional randomized Phase III trials to show benefit from a new treatment regimen may not b...

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)

2018-04-30

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

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group.

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Moritake, Hiroshi; Kamimura, Sachiyo; Nunoi, Hiroyuki; Nakayama, Hideki; Suminoe, Aiko; Inada, Hiroko; Inagaki, Jiro; Yanai, Fumio; Okamoto, Yasuhiro; Shinkoda, Yuichi; Shimomura, Maiko; Itonaga, Nobuyoshi; Hotta, Noriko; Hidaka, Yasufumi; Ohara, Osamu; Yanagimachi, Masakatsu; Nakajima, Noriko; Okamura, Jun; Kawano, Yoshifumi

2014-07-01

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu-Yamaguchi Children's Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

Detection of Anti-Asparaginase Antibodies During Therapy with E.coli Asparaginase in Children with Newly Diagnosed Acute Lymphoblastic Leukemia and Lymphoma

International Nuclear Information System (INIS)

EBEID, E.N.; KAMEL, M.M.; ALI, B.A.

2008-01-01

41 patients (83%) out of 50 patients had positive anti asparaginase antibodies at week 10 and week 21 of continuation phase respectively. The 2-year EFS of the whole group was 50%. There was no statistically significant relation between positivity of antiasparaginase antibodies and the following: age, gender, hypersensitivity reaction, response to therapy and EFS. Conclusion: The presence of anti asparaginase antibodies was unrelated to age, gender, hypersensitivity reaction, response to therapy and event free survival of newly diagnosed children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Gene Dose Effects of GSTM1, GSTT1 and GSTP1 Polymorphisms on Outcome in Childhood Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Borst, Louise; Buchard, Anders; Rosthoj, Susanne

2012-01-01

Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods...

Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells.

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Morita, Ken; Noura, Mina; Tokushige, Chieko; Maeda, Shintaro; Kiyose, Hiroki; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Yoshida, Kenichi; Ozaki, Toshifumi; Matsuo, Hidemasa; Ogawa, Seishi; Liu, Pu Paul; Nakahata, Tatsutoshi; Sugiyama, Hiroshi; Adachi, Souichi; Kamikubo, Yasuhiko

2017-11-30

Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

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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

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.

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Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

2010-04-01

About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Osteogenesis imperfecta and acute lymphoid leukemia: case report

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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.

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

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...

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.

The role of parvovirus B19 and the immune response in the pathogenesis of acute leukemia.

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Kerr, Jonathan R; Mattey, Derek L

2015-05-01

In this article, we review the evidence suggesting a possible role for B19 virus in the pathogenesis of a subset of cases of acute leukemia. Human parvovirus B19 infection may complicate the clinical course of patients with acute leukemia and may also precede the development of acute leukemia by up to 180 days. Parvovirus B19 targets erythroblasts in the bone marrow and may cause aplastic crisis in patients with shortened-red cell survival. Aplastic crisis represents a prodrome of acute lymphoblastic leukemia in 2% patients. There is a significant overlap between those HLA classes I and II alleles that are associated with a vigorous immune response and development of symptoms during B19 infection and those HLA alleles that predispose to development of acute leukemia. Acute symptomatic B19 infection is associated with low circulating IL-10 consistent with a vigorous immune response; deficient IL-10 production at birth was recently found to be associated with subsequent development of acute leukemia. Anti-B19 IgG has been associated with a particular profile of methylation of human cancer genes in patients with acute leukemia, suggesting an additional hit and run mechanism. The proposed role for parvovirus B19 in the pathogenesis of acute leukemia fits well with the delayed infection hypothesis and with the two-step mutation model, which describes carriage of the first mutation prior to birth, followed by suppression of hematopoiesis, which allows rapid proliferation of cells harboring the first mutation, acquisition of a second activating mutation, and expansion of cells carrying both mutations, resulting in acute leukemia. Copyright © 2015 John Wiley & Sons, Ltd.

The biology and targeting of FLT3 in pediatric leukemia

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Colleen eAnnesley

2014-09-01

Full Text Available Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high risk groups of acute myeloid leukemia (AML and acute lymphoblastic leukemia (ALL, as well as for relapsed leukemia, remains poor. Intensified chemotherapy regimens have somewhat improved success rates, but at the cost of drastically increased morbidity and long term adverse effects. With the success of imatinib in Philadelphia-chromosome positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over the past 15 years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3. FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high risk pediatric AML and in certain high risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy.

Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

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Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

2017-10-01

Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

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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

Is high dose methotrexate without irradiation of the brain sufficiently effective in prevention of CNS disease in children with acute lymphoblastic leukemia?

International Nuclear Information System (INIS)

Cap, J.; Foltinova, A.; Kaiserova, E.; Mojzesova, A.; Sejnova, D.; Jamarik, M.

1998-01-01

We present 5-year results of treatment in 93 children suffering from acute lymphoblastic leukemia using two therapeutic protocols containing multidrug chemotherapy including high dose methotrexate. We could ascertain different results in standard and high risk patients. In a group of 62 children with standard risk we observed improvement in complete remission rate being 98.9% after induction phase of therapy, only one patient died on septicemia. Relapse rate in this group was 21.2% and that 14. 7% in the bone marrow and 6.5% in CNS and no testicular relapse at all. In the group of 31 children with high risk leukemia all patients achieved complete remission. Only one of them died on acute pancreatitis due to toxicity. Overall relapse rate in this group was 28.9% with 12.8% of medullary relapse and 16.1 % of CNS relapse. The last one was significantly higher than in the previous study when brain irradiation was a part of therapeutic procedure. It seems that this treatment is effective mainly in the standard risk leukemia, however, in the high risk leukemias this procedure appears to be less effective in preventing CNS leukemia. In this group of patients irradiation of the brain need to be enclosed in the therapy. (authors)

Effects of Guided Written Disclosure Protocol on mood states and psychological symptoms among parents of off-therapy acute lymphoblastic leukemia children.

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Martino, Maria Luisa; Freda, Maria Francesca; Camera, Flavia

2013-06-01

This study assesses the effects of Guided Written Disclosure Protocol on psychological distress in mothers and fathers of off-therapy acute lymphoblastic leukemia children. An experimental group participated in the writing intervention with a control group subject only to test-taking standards. The Symptom Questionnaire and Profile of Mood States were administered at baseline, post-intervention, and follow-up. Guided Written Disclosure Protocol had significant effects on the progressive reduction of anxiety, depression, somatic symptoms, hostility, tension-anxiety, and fatigue-inertia within the experimental group. However, the control group distress levels tended to worsen over time. The mediating role of emotional processing was highlighted.

Tamibarotene as maintenance therapy for acute promyelocytic leukemia: results from a randomized controlled trial.

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Shinagawa, Katsuji; Yanada, Masamitsu; Sakura, Toru; Ueda, Yasunori; Sawa, Masashi; Miyatake, Junichi; Dobashi, Nobuaki; Kojima, Minoru; Hatta, Yoshihiro; Emi, Nobuhiko; Tamaki, Shigehisa; Gomyo, Hiroshi; Yamazaki, Etsuko; Fujimaki, Katsumichi; Asou, Norio; Matsuo, Keitaro; Ohtake, Shigeki; Miyazaki, Yasushi; Ohnishi, Kazunori; Kobayashi, Yukio; Naoe, Tomoki

2014-11-20

The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL. Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years. A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated. In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study. © 2014 by American Society of Clinical Oncology.

A case of acute lymphoblastic leukemia complicated with spinal cord compression

International Nuclear Information System (INIS)

Abe, Yukiko; Uchiyama, Noboru; Endo, Norio

1985-01-01

A 14-year-old boy developed spinal cord compression during remission of acute lymphoblastic leukemia. Metrizamide myelography disclosed complete block at the level of the 8th thoracic vertebra. Subsequent metrizamide CT clearly showed the subarachnoid space compressed and stenosed from the 8th thoracic vertebra to the 2nd lumber verbetra, and an extradural mass compressing the spinal cord. The function in the lower extremities was almost completely recovered by radiation therapy with a total dose of 10 Gy from the 6th thoracic vertebra to the 4th lumbar vertebra. (Namekawa, K.)

Tunneling Schmorl's nodes in an elderly woman treated for acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Leone, A.; Cerase, A.; Equitani, F.; Pagano, L.

2000-01-01

We present a 70-year-old woman with pre-B acute lymphoblastic leukemia in whom serial imaging studies showed the development of multiple vertebral collapse, and communicating superior and inferior Schmorl's nodes creating a longitudinal channel (''tunneling'' Schmorl's nodes) through the anterior aspect of T12 to L3 vertebral bodies of her osteoporotic thoracolumbar spine. This was observed after achieving complete remission of the disease and during maintenance therapy. The finding is felt to be secondary to iatrogenic exacerbation of osteoporosis. (orig.)

Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

International Nuclear Information System (INIS)

Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

1978-01-01

The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

Treatment of Young Adults with Acute Lymphoblastic Leukemia.

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Kansagra, Ankit; Litzow, Mark

2017-06-01

Young adults with acute lymphoblastic leukemia are a distinctive category of patients, with substantial difference in disease biology and response to therapy; hence, they pose unique challenges and issues beyond those faced by children and older adults. Despite inferior survival compared to children, there is growing evidence to suggest that young adults have improved outcomes when treated with pediatric-based approaches. With better supportive care and toxicity management and multidisciplinary team and approach, we have made great improvement in outcomes of young adults with ALL. However, despite significant progress, patients with persistence of minimal residual disease have a poor prognosis. This review discusses current controversies in the management of young adults with ALL, outcomes following pediatric and adult protocols, and the role of allogeneic stem cell transplantation. We also explore recent advances in disease monitoring and highlight our approach to incorporation of novel therapies in the management of young adults with ALL.

Heme oxygenase-1: A new druggable target in the management of chronic and acute myeloid leukemia.

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Salerno, Loredana; Romeo, Giuseppe; Modica, Maria N; Amata, Emanuele; Sorrenti, Valeria; Barbagallo, Ignazio; Pittalà, Valeria

2017-12-15

Heme oxygenase-1 (HO-1) is the enzyme catalyzing the rate-limiting oxidative degradation of cellular heme into free iron, carbon monoxide (CO), and biliverdin, which is then rapidly converted into bilirubin. By means of these catabolic end-products and by removal of pro-oxidant heme, HO-1 exerts antioxidant, antiapoptotic, and immune-modulating effects, leading to overall cytoprotective and beneficial functions in mammalian cells. Therefore, HO-1 is considered a survival molecule in various stress-related conditions. By contrast, growing evidence suggests that HO-1 is a survival-enhancing molecule also in various solid and blood cancers, such as various types of leukemia, promoting carcinogenesis, tumor progression, and chemo-resistance. Among leukemias, chronic myeloid leukemia (CML) is currently therapeutically well treated with tyrosine kinase inhibitors (TKIs) such as Imatinib (IM) and its congeners; nevertheless, resistance to all kinds of current drugs persist in a number of patients. Moreover, treatment outcomes for acute myeloid leukemia (AML) remain unsatisfactory, despite progress in chemotherapy and hematopoietic stem cell transplantation. Therefore, identification of new eligible targets that may improve leukemias therapy is of general interest. Several recent papers prove that inhibition of HO-1 through HO-1 inhibitors as well as modulation of other pathways involving HO-1 by a number of different new or known molecules, are critical for leukemia treatment. This review summarizes the current understanding of the pro-tumorigenic role of HO-1 and its potential as a molecular target for the treatment of leukemias. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Understanding Health Care Costs in a Wisconsin Acute Leukemia Population

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Patricia Steinert

2016-08-01

Full Text Available Purpose: We investigated factors driving health care costs of patients with a diagnosis of acute myeloid and acute lymphoblastic leukemia. Methods: Standard costs identified in insurance claims data obtained from the Wisconsin Health Information Organization were used in a sample of 837 acute leukemia patients from April 2009 to June 2011. The Andersen behavioral model of health care utilization guided selection of patient and community factors expected to influence health care costs. A generalized linear model fitting gamma-distributed data with log-link technique was used to analyze cost. Results: Type of treatment received and disease severity represented significant cost drivers, and patients receiving at least some of their treatment from academic medical centers experienced higher costs. Inpatient care and pharmacy costs of patients who received treatment from providers located in areas of higher poverty experienced lower costs, raising questions of potential treatment and medical practice disparities between provider locations. Directions of study findings were not consistent between different types of services received and underscore the complexity of investigating health care cost. Conclusions: While prevalence of acute leukemia in the United States is low compared to other diseases, its extreme high cost of treatment is not well understood and potentially influences treatment decisions. Acute leukemia health care costs may not follow expected patterns; further exploration of the relationship between cost and the treatment decision, and potential treatment disparities between providers in different socioeconomic locations, is needed.

High concordance of subtypes of childhood acute lymphoblastic leukemia within families

DEFF Research Database (Denmark)

Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A

2012-01-01

Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

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

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.

Philadelphia chromosome-positive adult acute leukemia with monosomy of chromosome number seven: a subgroup with poor response to therapy.

Science.gov (United States)

Maddox, A M; Keating, M J; Trujillo, J; Cork, A; Youness, E; Ahearn, M J; McCredie, K B; Freireich, E J

1983-01-01

Thirty-four adult patients were seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas between 1969 and 1980 with acute leukemia (AL) and a deleted G-group chromosome that was shown by Giemsa banding to be a Philadelphia (Ph1) chromosome t(9;22) in 21 patients. Fourteen had the Ph1 chromosome as the sole abnormality, 12 had the Ph1 chromosome and loss of one chromosome of the C-group (identified by Giemsa banding analysis as number 7 in eight patients), while eight had the Ph1 chromosome and other changes. These three groups were similar in sex, age distribution and hematologic parameters. The median age of 40 was lower than usually seen in AL. The distribution of the morphologic subtypes was similar to that seen at this institution, with 50% being acute myeloblastic, 12% acute myelomonocytic, 20% lymphoblastic and 18% acute undifferentiated. The complete remission rate with chemotherapy was low: 25% in the Ph1 +/- 7, 50% in the Ph1 +/other group and 43% in the Ph1 +/other group. Median survival time was 8 months for the Ph1 +/- 7 group, 5.5 months for the Ph1 +/other group and 9.0 months for the Ph1 +/alone group. These patients with Ph1 + AL had higher white blood cell counts, increased extramedullary disease and poorer responses to therapy than usual for patients with AL. The deletion of chromosome 7 and the acquisition of the Ph1 chromosome identifies a group of patients with characteristics similar to all the patients with Ph1 + AL but a poor response to therapy and short remission duration.

Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

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Harsh Shah

2015-01-01

Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

Imitation of Mb. perthes through acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Zaunschirm, A.; Muntean, W.; Kaulfersch, W.; Kurz, R.; Ritter, G.; Schneider, G.

1983-01-01

A two year old boy was seen in the orthopedic clinics because of typical symptoms of Legg-Perthes disease, a scintigraphy with Technetium sup(99m) showed a distinct deficiency of nuclear activity in the femoral head which is characteristic of the early stage of Legg-Perthes disease. A routine blood count lead to the diagnosis of acute lymphoblastic leukemia. The boy was treated according to the Austrian cooperative leukemia protocol and complete remission was achieved. No orthopedic treatment of the femur head necrosis was done, after eight weeks of treatment with multiagent chemotherapy the boy started to walk again and subsequently became free of all symptoms of Legg-Perthes disease. A scintigraphy done eight weeks after the initial scintigraphy showed that the deficiency of radionuclear activity of the femoral head was nearly vanished. This case illustrates the variability of bone involvement in acute lymphoblastic leukemia, which often is the most prominent symptom at an early stage of the disease. (Author)

Radiotherapy for leukemia in children, (1)

International Nuclear Information System (INIS)

Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro

1983-01-01

Following the development of effective chemotherapy for producing remissions of acute lymphocytic leukemia (ALL), a new phenomenon has emerged in this disease--central nervous system (CNS) leukemia. CNS leukemia has become an increasingly frequent obstacle to prolongation of initial complete remission. Prophylactic irradiation of the CNS concomitant with intrathecal administration of methotrexate (IT-MTX) has proved to be effective in the reduction of CNS involvement. The purpose of this paper is to describe the results of irradiation for prevention of CNS leukemia and to discuss their implications. The patients consisted of 32 children with acute leukemia, admitted to MAIZURU National Hospital from 1966 to 1980; 22 patients of them had ALL, the others ANLL (acute non-lymphocytic leukemia). Preventive CNS therapy was started in 1974, (group A), but there was no prevention before 1974 (group B). 1. In group B, six patients was treated by therapeutic cranial irradiation, but all cases resulted in death. 2. In group A, seven patients was treated by prophylactic cranial irradiation combined with IT-MTX, and all of them have been alive without CNS relapse for 2 to 4 2/3 years after therapy. 3. In group A, none of 7 patients (0 %) relapsed CNS leukemia initially as compared to 7 (50 %) of 14 in group B, thus preventive efficacy was clear. 4. There were no severe complications attributable to the radiotherapy, with or without IT-MTX. (author)

Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic leukemia.

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Stefano Tiziani

Full Text Available The tumor microenvironment is emerging as an important therapeutic target. Most studies, however, are focused on the protein components, and relatively little is known of how the microenvironmental metabolome might influence tumor survival. In this study, we examined the metabolic profiles of paired bone marrow (BM and peripheral blood (PB samples from 10 children with acute lymphoblastic leukemia (ALL. BM and PB samples from the same patient were collected at the time of diagnosis and after 29 days of induction therapy, at which point all patients were in remission. We employed two analytical platforms, high-resolution magnetic resonance spectroscopy and gas chromatography-mass spectrometry, to identify and quantify 102 metabolites in the BM and PB. Standard ALL therapy, which includes l-asparaginase, completely removed circulating asparagine, but not glutamine. Statistical analyses of metabolite correlations and network reconstructions showed that the untreated BM microenvironment was characterized by a significant network-level signature: a cluster of highly correlated lipids and metabolites involved in lipid metabolism (p<0.006. In contrast, the strongest correlations in the BM upon remission were observed among amino acid metabolites and derivatives (p<9.2 × 10(-10. This study provides evidence that metabolic characterization of the cancer niche could generate new hypotheses for the development of cancer therapies.

SUMOylation of sPRDM16 promotes the progression of acute myeloid leukemia

International Nuclear Information System (INIS)

Dong, Song; Chen, Jieping

2015-01-01

In addition to genetic and epigenetic alteration, post-translational modification of proteins plays a critical role in the initiation, progression and maturation of acute myeloid leukemia (AML). The SUMOylation site of sPRDM16 at K568 was mutated to arginine by site-directed mutagenesis. THP-1 acute myeloid leukemia cells were transduced with a lentivirus containing wild type or K568 mutant sPRDM16. Proliferation, self-renewal and differentiation of transduced THP-1 cells were analyzed both in vitro cell culture and in mouse xenografts. Gene expression profiles were analyzed by RNA-seq. Overexpression of sPRDM16 promoted proliferation, enhanced self-renewal capacity, but inhibited differentiation of THP-1 acute myeloid leukemia cells. We further confirmed that K568 is a bona fide SUMOylation site on sPRDM16. Mutation of the sPRDM16 SUMOylation site at K568 partially abolished the capacity of sPRDM16 to promote proliferation and inhibit differentiation of acute myeloid leukemia cells both in vitro and in mouse xenografts. Furthermore, THP-1 cells overexpressing sPRDM16-K568R mutant exhibited a distinct gene expression profile from wild type sPRDM16 following incubation with PMA. Our results suggest that K568 SUMOylation of sPRDM16 plays an important role in the progression of acute myeloid leukemia

FLT3 mutations in canine acute lymphocytic leukemia

International Nuclear Information System (INIS)

Suter, Steven E; Small, George W; Seiser, Eric L; Thomas, Rachael; Breen, Matthew; Richards, Kristy L

2011-01-01

FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations. We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting. The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations. These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias

Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Science.gov (United States)

2018-02-16

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

[Value of immunologic phenotyping of acute leukemias in children].

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Vannier, J P; Bene, M C

1989-10-01

Immunologic typing has demonstrated considerable heterogeneity among the acute leukemias. The most significant recent advance has been development of monoclonal antibody techniques. Some markers identified using these techniques seem to be specific for a given stage of maturation of one lymphoid or myeloid cell line. Most acute lymphoblastic leukemias (ALLs) are malignant proliferations whose differentiation appears to have become 'stuck' at one stage of maturation. Results of immunologic typing correlate well with the other clinical and biological data. For prognostic purposes, several patterns can be identified. Among B line ALLs, four varieties have been differentiated, i.e., CD10 negative ALLs, common ALLs, pre-B ALLs, and B ALLs. T ALLs include a broad spectrum of heterogeneous proliferations whose immunologic classification is made difficult by the large number of phenotypes encountered. Among acute myeloblastic leukemias (AMLs), some highly undifferentiated forms have been recognized, by means of immunologic typing, as originating in one of the myeloid cell lines. However, the nosologic and prognostic significance of these studies is less obvious than in ALLs.

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*

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Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

Frequency and Reasons for Return to Acute Care in Leukemia Patients Undergoing Inpatient Rehabilitation

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Fu, Jack Brian; Lee, Jay; Smith, Dennis W.; Bruera, Eduardo

2012-01-01

Objective To assess the frequency and reasons for return to the primary acute care service among leukemia patients undergoing inpatient rehabilitation. Design Retrospective study of all patients with leukemia, myelodysplastic syndrome, aplastic anemia, or myelofibrosis admitted to inpatient rehabilitation at a tertiary referral-based cancer center between January 1, 2005, and April 10, 2012. Items analyzed from patient records included return to the primary acute care service with demographic information, leukemia characteristics, medications, hospital admission characteristics, and laboratory values. Results 225 patients were admitted a total of 255 times. 93/255 (37%) of leukemia inpatient rehabilitation admissions returned to the primary acute care service. 18/93 (19%) and 42/93 (45%) of these patients died in the hospital and were discharged home respectively. Statistically significant factors (p<.05) associated with return to the primary acute care service include peripheral blast percentage and the presence of an antifungal agent on the day of inpatient rehabilitation transfer. Using an additional two factors (platelet count and the presence of an antiviral agent both with a p<.11), a Return To Primary (RTP) - Leukemia index was formulated. Conclusions Leukemia patients with the presence of circulating peripheral blasts and/or antifungal agent may be at increased risk of return to the primary acute care service. The RTP-Leukemia index should be tested in prospective studies to determine its usefulness. PMID:23117267

Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

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Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

2010-06-07

Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Bradycardia during Induction Therapy with All-trans Retinoic Acid in Patients with Acute Promyelocytic Leukemia: Case Report and Literature Review

Directory of Open Access Journals (Sweden)

Pin-Zi Chen

2018-01-01

Full Text Available A 41-year-old man with newly diagnosed acute promyelocytic leukemia (APL received induction chemotherapy, containing all-trans retinoic acid (ATRA, idarubicin, and arsenic trioxide. On the 11th day of therapy, he experienced complete atrioventricular (AV block; therefore, ATRA and arsenic trioxide were immediately postponed. His heart rate partially recovered, and ATRA was rechallenged with a half dose. However, complete AV block as well as differentiation syndrome recurred on the next day. ATRA was immediately discontinued, and a temporary pacemaker was inserted. Two days after discontinuing ATRA, AV block gradually improved, and ATRA was uneventfully rechallenged again. The Naranjo adverse drug reaction probability scale was 7 for ATRA, suggesting it was the probable cause of arrhythmia. A literature search identified 6 other cases of bradycardia during ATRA therapy, and all of them occurred during APL induction therapy, with onset ranging from 4 days to 25 days. Therefore, monitoring vital signs and performing electrocardiogram are highly recommended during the first month of induction therapy with ATRA. ATRA should be discontinued if complete AV block occurs. Rechallenging with ATRA can be considered in fully recovered and clinically stable patients.

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...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

Bacteremia due to Aeromonas hydrophila in Acute Lymphoblastic Leukemia

International Nuclear Information System (INIS)

Fatima, A.; Afridi, F.I.; Farooqi, B.J.; Qureshi, A.; Hussain, A.

2013-01-01

Aeromonas hydrophila (A. hydrophila) is a low virulent organism but may cause devastating fatal infections in immunocompromised host especially in liver cirrhosis. It is rarely reported to cause septicemia in a patient with Acute Lymphoblastic Leukemia (ALL). The mortality rate of septicemia due to A. hydrophila is 29% to 73%. We report a case of 59-year-old female patient who was a known case of ALL, presented with the complaints of fever, lethargy and generalized weakness for one month. After taking blood samples for investigations, empirical antimicrobial therapy was started. She did not improve after 48 hours of therapy. Meanwhile blood culture revealed pure growth of A. hydrophila. After sensitivity report was available, ciprofloxacin was started. Patient became afebrile after 48 hours of treatment with ciprofloxacin. It is very vital to correctly identified and treat bacteremia due to A. hydrophila especially in the underlying leukemic patient. (author)

Identification of an MLC suppressor cell population in acute leukemia

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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

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.

INCIDENCE OF ACUTE MYELOID LEUKEMIA AFTER BREAST CANCER

Directory of Open Access Journals (Sweden)

Caterina Giovanna Valentini

2011-12-01

Full Text Available Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients

Acute myeloid leukemia in a patient with constitutional 47,XXY karyotype