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Sample records for lymphoma acute lymphoblastic

  1. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  2. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

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    2017-07-06

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  3. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

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    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  4. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

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    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

  5. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes

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    Chang Hung

    2012-02-01

    Full Text Available Abstract Concurrent hematologic malignancies are relatively rare. We encountered a case of concurrent acute myeloid leukemia (AML and T lymphoblastic lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(5;12(q33;p13, which indicated presence of PDGFRB gene translocations. Therefore, this disease belongs to the new WHO category of myeloid and lymphoid neoplasms with abnormalities in PDGFRA, PDGFRB and FGFR1 genes. Although such genetic mutations are prone to multi-lineage differentiation, the present case is in fact the first report of concurrent AML and T lymphoblastic lymphoma involving PDGFRB mutations. The patient was treated with cytarabine and daunomycin in combination with high dose dexamethasone. Allogeneic stem cell transplantation was performed after successful remission induction for both entities. The patient eventually died of chronic graft-versus-host-disease related infection. Based on such an experience, we suggest the decision of stem cell transplantation should be weighed carefully against the risks, especially when tyrosine kinase inhibitors are safe and potentially effective in dealing with such entities.

  6. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

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    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  7. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

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    Labar, Boris; Suciu, Stefan; Willemze, Roel; Muus, Petra; Marie, Jean-Pierre; Fillet, Georges; Berneman, Zwi; Jaksic, Branimir; Feremans, Walter; Bron, Dominique; Sinnige, Harm; Mistrik, Martin; Vreugdenhil, Gerard; De Bock, Robrecht; Nemet, Damir; Gilotay, Caroline; Amadori, Sergio; de Witte, Theo

    2010-01-01

    Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative

  8. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  9. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  10. Lymphoblastic lymphoma involving multiple vertebrae.

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    Li, Da; Xu, Yu-Lun; Wu, Zhen

    2017-09-26

    Acute lymphoblastic lymphoma (ALL) was a malignant hematological disease in childhood but rarely, initially involved epidural compartment in adult. A 20-year-old male presented with progressive osphyalgia for 2 months and left lower motor weakness for 2 weeks with constipation. Physical examination revealed decreased muscle strength and numbness of left lower limb, and abnormal gait. Contrasted MRI showed multiple vertebrae of hypointense T1 signals (C2/C4/C7/T5/T8/T9/T12/L2/L4) and an intraspinal epidural lesion (L2-4). Subtotal resection was achieved. Histopathology suggested malignant B-cell lymphoma with Ki-67 of 90% and positivity of leukocyte common antigen (LCA). A bone marrow biopsy was unequivocally diagnostic of B-cell ALL followed by chemotherapy (Methotrexate) and partial recovery was observed. The present case was the oldest patient with epidural ALL. The radiographic changes in multiple vertebrae suggested metabolic, hematological, or granulomatous disease. The marrow biopsy was necessary if without hypercalcemia and abnormal peripheral blood examination. Accurate pathological diagnosis was essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

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    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).

  12. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

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    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  13. A fatal case of acute pulmonary embolism caused by right ventricular masses of acute lymphoblastic lymphoma-leukemia in a 13 year old girl

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    Yu Mi Ko Ko

    2012-07-01

    Full Text Available We report a case of a 13-year-old girl with acute lymphoblastic lymphoma- leukemia, who presented with a cardiac metastasis in the right ventricle, resulting in a pulmonary embolism. At the time of her leukemia diagnosis, a cardiac mass was incidentally found. The differential diagnosis for this unusual cardiac mass included cardiac tumor, metastasis, vegetation, and thrombus. Empirical treatment was initiated, including anticoagulation and antibiotics. She underwent plasmapheresis and was administered oral prednisolone for her leukemia. Five days later, she experienced sudden hemodynamic collapse and required extracorporeal membrane oxygenation insertion and emergency surgery. These interventions proved futile, and the patient died. Pathology revealed that the cardiac mass comprised an aggregation of small, round, necrotic cells consistent with leukemia. This is the first known case of acute lymphoblastic leukemia presenting as a right ventricular mass, with consequent fatal acute pulmonary embolism. A cardiac mass in a child with acute leukemia merits investigation to rule out every possible etiology, including vegetation, thrombus, and even a mass of leukemic cells, which could result in the fatal complication of pulmonary embolism.

  14. Effects of microRNA-21 on the biological functions of T-cell acute lymphoblastic lymphoma/leukemia

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    Shi, Cunzhen; Zhang, Xudong; Li, Xin; Zhang, Lei; Li, Ling; Sun, Zhenchang; Fu, Xiaorui; Wu, Jingjing; Chang, Yu; Li, Wencai; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that miR-21 expression in Jurkat cells was markedly upregulated. Furthermore, upregulating miR-21 expression in Jurkat cells promoted cell proliferation and invasion and decreased the apoptosis rate. By contrast, knockdown of miR-21 in Jurkat cells suppressed proliferation and invasion and increased the apoptosis rate. Furthermore, the results indicated that signal transducer and activator of transcription (STAT) 3 was targeted by miR-21, and that miR-21 inhibited STAT3 expression at the protein level rather than at the messenger RNA level. In conclusion, targeting the inhibition of miR-21 may be a novel therapeutic strategy for patients with T-ALL. PMID:27895788

  15. Childhood Acute Lymphoblastic Leukemia

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    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...

  16. True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms.

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    Bouabdallah, R; Abéna, P; Chetaille, B; Aurran-Schleinitz, T; Sainty, D; Dubus, P; Arnoulet, C; Coso, D; Xerri, L; Gastaut, J A

    2001-06-01

    True histiocytic lymphoma (THL) is a very rare type of non-Hodgkin's lymphoma (NHL) in which neoplastic cells exhibit markers of histiocytic differentiation. Some cases of THL have been reported in patients with previous acute lymphoblastic leukaemia (ALL), especially in children and young adults, in whom the acute leukaemia was of T-cell origin. The relationship between the initial lymphoid tumour and the secondary THL remains unclear, as a common monoclonal origin shared by both neoplasms has never been definitively demonstrated. We report a patient with B-ALL who developed a nodal and extranodal tumour with histological and immunohistochemical features of THL 4 years after the initial diagnosis. Genotypic study showed that both neoplasms contained the same immunoglobulin heavy gene rearrangement, which has not been reported previously.

  17. Precursor B-Cell Acute Lymphoblastic Leukemia/Lymphoma with L3 Morphology, Philadelphia Chromosome, MYC Gene Translocation, and Coexpression of TdT and Surface Light Chains: A Case Report

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    Alicia C. Hirzel

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia is predominantly found in children. It is a neoplasm of precursor cells or lymphoblasts committed to either a B- or T-cell lineage. The immature cells in B-acute lymphoblastic leukemia/lymphoma can be small or medium sized with scant or moderate cytoplasm and typically express B-cell markers such as CD19, cytoplasmic CD79a, and TdT without surface light chains. These markers, along with cytogenetic studies, are vital to the diagnosis, classification, and treatment of these neoplasms. We present an unusual case of a precursor B-cell ALL, in an 82-year-old woman, who presented with pancytopenia and widespread lymphadenopathy. The cells show L3 morphology (Burkitt-like lymphoma with coexpression of TdT and surface light chains in addition to an MYC gene translocation and Philadelphia chromosome.

  18. Adult Acute Lymphoblastic Leukemia

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    Faderl, Stefan; O’Brien, Susan; Pui, Ching-Hon; Stock, Wendy; Wetzler, Meir; Hoelzer, Dieter; Kantarjian, Hagop M.

    2016-01-01

    Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. PMID:20101737

  19. Biomarker analysis and clinical relevance of TK1 on the cell membrane of Burkitt’s lymphoma and acute lymphoblastic leukemia

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    Weagel EG

    2017-09-01

    Full Text Available Evita G Weagel,1 Wei Meng,1 Michelle H Townsend,1 Edwin J Velazquez,1 Rachel A Brog,1 Michael W Boyer,2 K Scott Weber,1 Richard A Robison,1 Kim L O’Neill1 1Department of Microbiology and Molecular Biology, Brigham Young University, Provo, 2Division of Hematology and Hematologic Malignancies, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA Abstract: TK1 is an enzyme involved in DNA synthesis and repair. TK1 is usually found elevated in cancer patients’ serum, which makes it a useful tumor proliferation biomarker that strongly correlates with cancer stage, metastatic capabilities, and recurrence risk. In this study, we show that TK1 is upregulated and localizes on the plasma membrane of Burkitt’s lymphoma, acute promyelocytic leukemia, T cell leukemia, and acute lymphoblastic leukemia (ALL. Using flow cytometry, we confirmed that TK1 localizes on the surface of Raji, HL60, and Jurkat cell lines and on ALL clinical samples. Using fluorescent microscopy, we found a strong association of TK1 with the plasma membrane in Raji, HL60, and Jurkat cell lines. These findings were also confirmed by scanning electron microscopy. Our study also shows that this phenomenon does not occur on normal resting or proliferating lymphocytes. In addition, we show that membrane TK1 is found in all oligomeric forms ranging from monomer to tetramer and exhibits enzymatic activity. These findings suggest TK1 as a possible target for immunotherapy with the potential to be utilized in the treatment of hematological cancers. Keywords: Burkitt’s lymphoma, acute lymphoblastic leukemia, ALL, thymidine kinase 1, surface antigen

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

    Science.gov (United States)

    2016-10-24

    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

  1. 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

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    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

  2. Mediastinal involvement in adults with lymphoblastic lymphoma

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    Schwartz, E.E.; Conroy, J.F.; Bonner, H.

    Radiologic, clinical, and pathologic findings are described in 6 young adults with lymphoblastic lymphoma (LBL), an aggressive tumor which has recently become recognized as a serious threat to adults as well as to children. Each patient presented with a mediastinal mass, three of them developing cardiac tamponade and one a superior vena cava syndrome. CT scanning and echocardiography were particularly helpful in defining the lesions. The rapid dissemination of LBL, and its early progression to a leukemic phase call for promt diagnosis and treatment.

  3. Stem cell transplantation outcomes in lymphoblastic lymphoma.

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    Brammer, Jonathan E; Khouri, Issa; Marin, David; Ledesma, Celina; Rondon, Gabriela; Ciurea, Stefan O; Nieto, Yago; Champlin, Richard E; Hosing, Chitra; Kebriaei, Partow

    2017-02-01

    Lymphoblastic lymphoma (LBL) is an aggressive lymphoma pathologically similar to lymphoblastic leukemia, but primarily presents with nodal or extra-medullary involvement. The aim of this study is to describe outcomes of patients undergoing stem cell transplantation (SCT) for LBL compared to historical data. Thirty-nine patients, of which 54% lacked complete remission (CR), received SCT for LBL between 1990 and 2015; 31 allogeneic and eight autologous. Overall survival (OS) and progression free survival (PFS) at three years for the entire cohort was 41%, the cumulative incidence (CI) of non-relapse mortality (NRM) was 18% at one year, and CI relapse mortality was 28% at one-year and 36% at three years; results similar to historical reports. On multivariate analysis, the use of total-body irradiation (TBI) based conditioning and transplantation in CR were independently predictive of OS and PFS. For patients requiring SCT for LBL, CR and TBI-based conditioning prior to allogeneic SCT may provide improved disease control.

  4. Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951.

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    De Moerloose, Barbara; Suciu, Stefan; Bertrand, Yves; Mazingue, Françoise; Robert, Alain; Uyttebroeck, Anne; Yakouben, Karima; Ferster, Alice; Margueritte, Geneviève; Lutz, Patrick; Munzer, Martine; Sirvent, Nicolas; Norton, Lucilia; Boutard, Patrick; Plantaz, Dominique; Millot, Frederic; Philippet, Pierre; Baila, Liliana; Benoit, Yves; Otten, Jacques

    2010-07-08

    The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.

  5. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  6. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

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    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  7. Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951

    Science.gov (United States)

    Suciu, Stefan; Bertrand, Yves; Mazingue, Françoise; Robert, Alain; Uyttebroeck, Anne; Yakouben, Karima; Ferster, Alice; Margueritte, Geneviève; Lutz, Patrick; Munzer, Martine; Sirvent, Nicolas; Norton, Lucilia; Boutard, Patrick; Plantaz, Dominique; Millot, Frederic; Philippet, Pierre; Baila, Liliana; Benoit, Yves; Otten, Jacques

    2010-01-01

    The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m2/d), 201 to DEX (6 mg/m2/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster–based protocols, pulses should become a standard component of therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. PMID:20407035

  8. Outcome of children and adolescents with lymphoblastic lymphoma

    Directory of Open Access Journals (Sweden)

    Maria Christina Lopes Araújo Oliveira

    2015-10-01

    Full Text Available Summary Introduction: lymphoblastic lymphoma (LBL is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8. LBL had T-cell origin in 16 patients (59%. The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%. Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67% at diagnosis. Twenty-four patients (89% achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95, 22 patients (81% were alive in first complete remission. Five children (18.5% died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4. Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

  9. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  10. Transformation of Follicular Lymphoma to a High-Grade B-Cell Lymphoma With MYC and BCL2 Translocations and Overlapping Features of Burkitt Lymphoma and Acute Lymphoblastic Leukemia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Alina M Bischin

    2017-02-01

    Full Text Available Most commonly, histologic transformation (HT from follicular lymphoma (FL manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS. Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL with MYC and B-cell lymphoma protein 2 (BCL2 and/or BCL6 gene rearrangements, also known as “double-hit” or “triple-hit” lymphomas. In the 2016 revision of the World Health Organization (WHO classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit. Instead, the WHO introduced the HGBL category, characterized by MYC and BCL2 and/or BCL6 rearrangements. Cases that present as an intermediate phenotype of DLBCL and Burkitt lymphoma (BL will fall within this HGBL category. Very rarely, HT results in both the intermediate DLBCL and BL phenotypes and exhibits lymphoblastic features, in which case the WHO recommends that this morphologic appearance should be noted. In comparison with de novo patients with DLBCL, NOS, those with MYC and BCL2 and/or BCL6 gene rearrangements have a worse prognosis. A 63-year-old woman presented with left neck adenopathy. Laboratory assessments, including complete blood count, complete metabolic panel, serum lactate dehydrogenase, and β 2 -microglobulin, were all normal. A whole-body computerized tomographic (CT scan revealed diffuse adenopathy above and below the diaphragm. An excisional node biopsy showed grade 3A nodular FL. The Ki67 labeling index was 40% to 50%. A bone marrow biopsy showed a small focus of paratrabecular CD20+ lymphoid aggregates. She received 6 cycles of bendamustine (90 mg/m 2 on days +1 and +2 and rituximab (375 mg/m 2 on day +2, with each cycle delivered every 4 weeks. A follow-up CT scan at completion of therapy showed a partial response with resolution of axillary adenopathy and a dramatic shrinkage of the large retroperitoneal nodes. After 18 months, she had crampy

  11. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic Arthritis in a Nigerian boy. ... lead to delay in commencing appropriate treatment. ... of two months duration, had an elevated Rheumatoid factor and X-ray findings suggestive of ...

  12. Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma

    Science.gov (United States)

    Kundu, Mondira; Compton, Sheila; Garrett-Beal, Lisa; Stacy, Terryl; Starost, Matthew F.; Eckhaus, Michael; Speck, Nancy A.; Liu, P. Paul

    2005-01-01

    Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor β (CBFβ) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1lacZ/lacZ compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies. PMID:16051740

  13. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  14. Primary T-cell lymphoblastic lymphoma in the middle ear.

    Science.gov (United States)

    Li, Bo; Liu, Shixi; Yang, Hui; Wang, Weiya

    2016-03-01

    T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

  15. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  16. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-04-28

    Apr 28, 2013 ... Acute lymphoblastic leukaemia (ALL) accounts for about 77% of cases ... tosis with a White Blood Cell count (WBC) of greater than 30 x 109/L and ... tarsometatarsal, small interphalangeal joints of the feet and vertebrae.3 Our ...

  17. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

    Roman, Eve; Lightfoot, Tracy; Smith, Alexandra G

    2013-01-01

    BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes ( 4500 g), we pooled data from three of the largest childhood cancer case...

  18. Pre-treatment serum levels of interleukin-10, interleukin-12 and their ratio predict response to therapy and probability of event-free and overall survival in childhood soft tissue sarcomas, Hodgkin's lymphomas and acute lymphoblastic leukemias.

    Science.gov (United States)

    Bien, Ewa; Balcerska, Anna; Adamkiewicz-Drozynska, Elzbieta; Rapala, Malgorzata; Krawczyk, Malgorzata; Stepinski, Jan

    2009-07-01

    Deregulated serum IL-10, IL-12 and their reciprocal balance have been stated in malignancies of adults. In children with cancer the issue has not been investigated so far. To determine the diagnostic and prognostic roles of pre-treatment serum levels of IL-10 (Th2 cytokine), IL-12 (Th1) and their ratios (measured by the IL-10 and IL-12p70 ELISA kits; Endogen) in 91 children with soft tissue sarcomas (STS), Hodgkin's lymphomas (HL) and acute lymphoblastic leukemias (ALL). Median IL-10 and IL-12 levels were significantly higher in cancer patients than in healthy controls. Increased IL-10 indicated presence of general symptoms in HL and high risk group in ALL. Elevated IL-10 and IL-10/IL-12 ratios and decreased IL-12 correlated with poor-risk histology in STS, poor response to therapy, relapse and death from cancer. Multivariate analysis identified IL-10/IL-12 ratio>0.14 and IL-12<40 pg/mL as significant predictors for shorter EFS and OS, respectively. Pre-treatment serum levels of IL-10, IL-12 and IL-10/IL-12 balance in children with STS, HL and ALL may be of value as additional prognostic tools to predict the response to therapy and probability of EFS and OS.

  19. JAK Mutations in High-Risk Childhood Acute Lymphoblastic Leukemia

    National Research Council Canada - National Science Library

    Charles G. Mullighan; Jinghui Zhang; Richard C. Harvey; J. Racquel Collins-Underwood; Brenda A. Schulman; Letha A. Phillips; Sarah K. Tasian; Mignon L. Loh; Xiaoping Su; Wei Liu; Meenakshi Devidas; Susan R. Atlas; I-Ming Chen; Robert J. Clifford; Daniela S. Gerhard; William L. Carroll; Gregory H. Reaman; Malcolm Smith; James R. Downing; Stephen P. Hunger; Cheryl L. Willman; Janet D. Rowley

    2009-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations...

  20. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel.

    NARCIS (Netherlands)

    Oschlies, I.; Burkhardt, B.; Chassagne-Clement, C.; d'Amore, E.S.; Hansson, U.; Hebeda, K.M.; McCarthy, K.; Kodet, R.; Maldyk, J.; Mullauer, L.; Porwit, A.; Schmatz, A.I.; Tinguely, M.; Abramov, D.; Wotherspoon, A.; Zimmermann, M.; Reiter, A.; Klapper, W.

    2011-01-01

    The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacki

  1. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical....... There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal...... genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our...

  2. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

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

  3. Primary lymphoblastic B-cell lymphoma of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Miao-Xia He; Ming-Hua Zhu; Wei-Qiang Liu; Li-Li Wu; Xiong-Zeng Zhu

    2008-01-01

    Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo.Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site.Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

  4. 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.

  5. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    Science.gov (United States)

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell 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; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  6. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  7. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... lymphoblastic leukemia E.1.1.1Medical condition in easily understood language Acute lymphoblastic

  8. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  9. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    Science.gov (United States)

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  10. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  11. Acute lymphoblastic leukemia in adolescents and young adults in Finland.

    Science.gov (United States)

    Usvasalo, Anu; Räty, Riikka; Knuutila, Sakari; Vettenranta, Kim; Harila-Saari, Arja; Jantunen, Esa; Kauppila, Marjut; Koistinen, Pirjo; Parto, Katriina; Riikonen, Pekka; Salmi, Toivo T; Silvennoinen, Raija; Elonen, Erkki; Saarinen-Pihkala, Ulla M

    2008-08-01

    Interest has recently been paid to adolescents and young adults with acute lymphoblastic leukemia, particularly because all reports so far published indicate that these patients have a better outcome when treated with pediatric rather than adult therapeutic protocols. There are different biological subtypes of acute lymphoblastic leukemia with distinct features and prognoses; the distribution of these subtypes is not well known among adolescents. We, therefore, studied acute lymphoblastic leukemia in adolescents and young adults aged 10 to 25 years in Finland. This population-based study included 225 consecutive patients aged 10-25 years diagnosed with acute lymphoblastic leukemia during 1990-2004. One hundred and twenty-eight patients (10-16 years) were treated with pediatric Nordic (NOPHO) protocols, and 97 patients (17-25 years) with Finnish Leukemia Group National protocols. We characterized the biological subtypes, clinical features and outcome of these patients. For the whole cohort, the remission rate was 96%, 5-year event-free survival 62% and overall survival 72%. The 5-year event-free survival was 67% for the pediatric treatment group and 60% for the adult treatment group (p=n.s.). Patients with inferior outcome were those with a white blood cell count >or= 100 x 10(9)/L, the Philadelphia chromosome and MLL. Good prognostic features were TEL-AML1, hyperdiploidy, and pediatric intermediate risk stratification. Unlike all previous studies, we found that the outcome of adolescents and young adults with acute lymphoblastic leukemia treated with pediatric or adult therapeutic protocols was comparable. The success of the adult acute lymphoblastic leukemia therapy emphasizes the benefit of central referral of patients to academic centers and adherence to research protocols.

  12. Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma

    DEFF Research Database (Denmark)

    Hansen, P B; Kjeldsen, L; Dalhoff, K

    1992-01-01

    Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic...... determination of CSF-B2m alone may be a useful and sensitive marker of CNS-dissemination in acute leukemia and malignant lymphoma. Using the criteria of CSF-B2m greater than 160 nmol/l as a positive diagnostic test the sensitivity of the test was 100%, the specificity was 76%. The same values for the CSF...

  13. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  14. 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...

  15. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

    OpenAIRE

    2013-01-01

    T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatme...

  16. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-12-28

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

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

    Science.gov (United States)

    Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

    2013-01-01

    Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

  18. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  19. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. L-asparaginase treatment in acute lymphoblastic leukemia

    NARCIS (Netherlands)

    R. Pieters (Rob); S.P. Hunger (Stephen); J. Boos (Joachim); C. Rizzari (Carmelo); L.B. Silverman (Lewis); A. Baruchel (André); N. Goekbuget (Nicola); M. Schrappe (Martin); C.H. Pui (Ching-Hon)

    2011-01-01

    textabstractAsparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive a

  1. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

    Full Text Available Abstract Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

  2. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

    2003-01-01

    The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with t

  3. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  4. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing pa...

  5. Relationship between ABO blood group and Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tavasolian, F; Abdollahi, E; Vakili, M; Amini, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) constitute a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL affects both children and adults. Diagnosis is based on morphologic, immunophenotypic, and genetic features that allow differentiation from normal progenitors and other hematopoietic and nonhematopoietic neoplasms. The aim of this study was to investigate the association between ALL and ABO blood group. This is a case-control study that was carried out in Amir Oncology Hospital in Shiraz during 2011 to2013. The case group consisted of 293 patients with acute lymphoblastic leukemia. And compared with 300 subject in control group ( the age in the case group was between 2-5 year, and the age in the control group was between 2-45 year) .Statistical analyzes was done performed by chi -square test. The results was considered significant when p value ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128(O) in patient with Acute Lymphoblastic Leukemia and the blood group of 300 participants in the control group include, 63% (25) A, 69% (25.6) B, 18 % 06.8) AB and 101% (42.6) O. The ABO blood group distribution showed that there is significant differences between ABO blood group and patients with acute lymphoblastic leukemia . This study showed significant association between ALL and ABO blood group and showed that blood group AB was associated with a higher risk of All (p value<0.001).

  6. Epigenetics in MLL-rearranged infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    D.J.P.M. Stumpel (Dominique)

    2012-01-01

    textabstractNowadays the cure rate for children diagnosed with acute lymphoblastic leukemia (ALL) has exceeded 80%. Although this is considered to be one of the major successes in pediatric oncology, the subgroup of patients that did not benefit from the improved therapeutic strategies should not be

  7. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

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

  9. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  10. Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Dalhoff, Kim; Schmiegelow, Kjeld

    2008-01-01

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

  11. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

  12. CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

    Science.gov (United States)

    2016-12-04

    Acute Myeloid Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-cell Prolymphocytic Leukemia; T-cell Large Granular Lymphocytic Leukemia; Peripheral T-cell Lymphoma, NOS; Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma, Nasal Type; Enteropathy-type Intestinal T-cell Lymphoma; Hepatosplenic T-cell Lymphoma

  13. BIOMED-2引物系统检测 T 淋巴母细胞性淋巴瘤/急性淋巴细胞白血病中Ig/TCR基因重排%Detection of immunoglobulin and TCR gene rearrangements by PCR using BIOMED-2 multi-plex protocols in T lymphoblastie lymphoma and acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    潘鑫艳; 冯强; 黎贵芸; 杨长绍; 杨举伦; 王丽

    2015-01-01

    目的:探讨BIOMED-2引物系统检测T淋巴母细胞性淋巴瘤( T lymphoblastic lymphoma, T-LBL)/急性淋巴细胞白血病( acute lymphoblastic leukemia, ALL)患者免疫球蛋白( immunoglobulin, Ig)/T细胞受体基因( T-cell receptor, TCR)重排的敏感性,分析Ig/TCR基因重排方式。方法采用BIOMED-2引物系统扩增35例T-LBL/ALL中Ig/TCR重排基因,核酸分子异源双链凝胶电泳分析基因重排结果。结果35例T-LBL/ALL中16例检测出TCR基因重排,检出率为45.7%,其中TCRβ单重排6例(37.5%),TCRγ单重排4例(25.0%),TCRβ和 TCRγ双重排3例(18.8%),TCRδ单重排2例(12.5%),TCRγ和TCRδ双重排1例(6.3%)。4例患者同时检测出Ig和TCR基因重排,Ig基因检出率为11.4%。28例T-LBL中11例检测出TCR基因重排(39.3%),7例T-ALL中6例检测出TCR基因重排(85.7%)。结论利用BIOMED-2引物系统可检测出部分T-LBL患者的Ig/TCR基因重排,是一种辅助诊断工具。%Purpose To investigate the sensitivity of BIOMED-2 primer system in T lymphoblastic lymphoma ( T-LBL) and acute lym-phoblastic leukemia ( ALL) patients immunoglobulin ( Ig) and T-cell receptor ( TCR) gene rearrangement, and to analyze the co-rear-rangement pattern. Methods Amplification of rearranged Ig and TCR gene was performed in standard PCR in 35 T-LBL/ALL pa-tients. PCR products were analyzed by heteroduplex and polyacrylamide gel electrophoresis. Results 16 cases (45. 7%) of 35 sam-ples were detected to have TCR gene rearrangements, including 6 cases (37. 5%) of TCRβgene monoclonal rearrangements, 4 cases (25. 0%) of TCRγ gene monoclonal rearrangements, 3 cases (18. 8%) of TCRβ and TCRγ gene double rearrangements, 2 cases (12. 5%) of TCRδ gene monoclonal rearrangements and 1 case (6. 3%) of TCRγand TCRδgene double rearrangements were detec-ted. 4 cases (11. 4%) of 35 samples detected to have clonal immunoglobulin and TCR gene rearrangements. 11 cases (39. 3%) of 28 T-LBL patients were detected to

  14. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  15. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  16. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Directory of Open Access Journals (Sweden)

    Stephen E. Langabeer

    2016-01-01

    Full Text Available The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

  17. New decision support tool for acute lymphoblastic leukemia classification

    Science.gov (United States)

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  18. Acute lymphoblastic leukemia presenting with a uterine cervical mass

    Directory of Open Access Journals (Sweden)

    N Geetha

    2015-01-01

    Full Text Available Involvement of female genital tract with acute lymphoblastic leukemia (ALL is extremely rare, and it is even rarer for a patient to have symptomatic presentation. We report the case of a middle-aged lady with ALL, who presented with severe abnormal uterine bleeding and a uterine cervical mass. Biopsy of the cervical mass showed infiltration by leukemic blasts. She received chemotherapy with Berlin-Frankfurt-Munster protocol and is alive in remission after 10 years.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...... intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens...

  20. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    OpenAIRE

    Soosay Raj TA; Smith AM; Moore AS

    2013-01-01

    Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a...

  1. 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.)

  2. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

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

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

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

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  6. 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.

  7. Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); I.M. Appel (Inge); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2008-01-01

    textabstractCoagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecros

  8. The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; de Groot-Kruseman, Hester A.; te Winkel, Mariel L.; Fiocco, Martha; van den Akker, Erica L. T.; Hoogerbrugge, Peter; van den Berg, Henk; Leeuw, Jan A.; Bruin, Marrie C. A.; Bresters, Dorine; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Body mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composit

  9. Acute hepatitis A induction of precursor B-cell acute lymphoblastic leukemia: a causal relationship?

    Science.gov (United States)

    Senadhi, V; Emuron, D; Gupta, R

    2010-09-01

    Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with malaise for a month without spontaneous bruising/bleeding, infections, or B-symptoms, such as fevers, night sweats, or unintentional weight loss. Nonspecific viral transformation of bone marrow has been discussed in the literature, but we specifically describe hepatitis A-induced adult-onset precursor B-cell acute lymphoblastic leukemia, which is the first reported case in the literature.

  10. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  11. Retinoid-related orphan receptor γ (RORγ) adult induced knockout mice develop lymphoblastic lymphoma.

    Science.gov (United States)

    Liljevald, Maria; Rehnberg, Maria; Söderberg, Magnus; Ramnegård, Marie; Börjesson, Jenny; Luciani, Donatella; Krutrök, Nina; Brändén, Lena; Johansson, Camilla; Xu, Xiufeng; Bjursell, Mikael; Sjögren, Anna-Karin; Hornberg, Jorrit; Andersson, Ulf; Keeling, David; Jirholt, Johan

    2016-11-01

    RORγ is a nuclear hormone receptor which controls polarization of naive CD4(+) T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORγ has therapeutic potential for autoimmune diseases; however, this mechanism may potentially carry target-related safety risks, as mice deficient in Rorc, the gene encoding RORγ, develop T-cell lymphoma with 50% frequency. Due to the requirement of RORγ during development, the Rorc knockout (KO) animals lack secondary lymphoid organs and have a dysregulation in the generation of CD4+ and CD8+ T cells. We wanted to extend the evaluation of RORγ deficiency to address the question whether lymphomas, similar to those observed in the Rorc KO, would develop in an animal with an otherwise intact adult immune system. Accordingly, we designed a conditional RORγ knockout mouse (Rorc CKO) where the Rorc locus could be deleted in adult animals. Based on these studies we can confirm that these animals also develop lymphoma in a similar time frame as embryonic Rorc knockouts. This study also suggests that in animals where the gene deletion is incomplete, the thymus undergoes a rapid selection process replacing Rorc deficient cells with remnant thymocytes carrying a functional Rorc locus and that subsequently, these animals do not develop lymphoblastic lymphoma.

  12. Acute Lymphoblastic Leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available estigation E.1.1Medical condition(s) being investigated Acute Lymphoblastic Leukemia E.1.1.1Medical conditio...E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute lymphoblastic leukemia E.

  13. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

    Full Text Available Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002. Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  14. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  15. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

    Directory of Open Access Journals (Sweden)

    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  16. CLINICOPATHOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA - A MULTIPARAMETER STUDY

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    Jagannath

    2015-11-01

    Full Text Available BACKGROUND Acute Lymphoblastic Leukaemia (ALL, a malignancy of lymphoid lineage cells, has excellent prognosis in children. Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. AIMS & OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS & METHODS The present study (2014 was performed in the hematology section of Department of Pathology of Gajra Raja Medical College, Gwalior over a period of 12 months from 1st October 2013 to 30th September 2014. This was a prospective study. The blood samples were received from various departments of Jayarogya hospital especially from the Pediatric and Medicine departments. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukemia, 25(67.57% were male and 12(32.43%, were female, (male:female ratio: 2.1:1. 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27% while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients, and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal white blood cell (WBC count at presentation, 10.81% had leucopenia and 80% had leucocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

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

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

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

  18. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  19. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

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    Mine Şencan Eren

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination.

  20. Clonal origins of ETV6-RUNX1+ acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Alpar, D.; Wren, D.; Ermini, Luca;

    2015-01-01

    Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified...... by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned...

  1. A rare case of acute lymphoblastic leukaemia with hemophilia A

    Directory of Open Access Journals (Sweden)

    John Biju

    2009-12-01

    Full Text Available Abstract A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency. He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

  2. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

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

    Science.gov (United States)

    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

  4. 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

  5. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Soosay Raj TA

    2013-11-01

    Full Text Available Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL, a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory–motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI] formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR–ABL1 (Ph-negative (Ph- disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+ and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.Keywords: vincristine sulfate liposomal injection, liposomes, sphingosomal vincristine, acute lymphoblastic leukemia, chemotherapy

  6. CDX2 gene expression in acute lymphoblastic leukemia

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    Hanaa H. Arnaoaut

    2014-06-01

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

  7. 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

  8. Acute lymphoblastic leukemia: a comprehensive review and 2017 update

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-04-01

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

  10. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

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    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

  11. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

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

    Directory of Open Access Journals (Sweden)

    Ribera JM

    2015-06-01

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

  13. Non-Hodgkin lymphoma

    Science.gov (United States)

    Lymphoma - non-Hodgkin; Lymphocytic lymphoma; Histiocytic lymphoma; Lymphoblastic lymphoma; Cancer - non-Hodgkin lymphoma ... National Cancer Institute: PDQ adult non-Hodgkin lymphoma treatment. Bethesda, MD: National Cancer Institute. Updated ... . Accessed ...

  14. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  15. Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

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    Dania Lizet Quintanilla-Flores

    2014-01-01

    Full Text Available Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

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

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    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 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. PMID:28413626

  17. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  18. Subdural hemorrhages in acute lymphoblastic leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Rui Yin; CaiXia Qiu; XiaoHui Dong; YeLong Chen

    2016-01-01

    Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.

  19. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Bommer, M.; Hütter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  20. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Bommer, M.; Hutter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  1. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, Oliver G; Wassmann, Barbara

    2005-01-01

    Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL) includes at least one-quarter of all adults with ALL. Until recently, conventional chemotherapy programs that have been effective in other precursor B-cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic stem cell transplantation early in first remission has been the recommended therapy. The availability of imatinib mesylate and other tyrosine kinase inhibitors and small molecules that affect the BCR/ABL signaling pathways may be changing the treatment paradigm and the prognosis for these patients. The results from clinical trials using imatinib in the frontline setting and in relapsed patients as well as preliminary experience treating imatinib-resistant Ph(+) ALL will be described.

  2. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    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

  3. 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 pr

  4. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    ... with Acute Lymphoblastic Leukaemia: A Case Report and Review of Literature. ... vincristine treatment triggering the expression of asymptomatic CMT disease. ... Results: Facial nerve palsy, increasing lower extremities muscle weakness ...

  5. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    Alasia Datonye

    into vincristine therapy in a ten year old male on treatment for acute lymphoblastic ... diagnosis of malignancy to identify any undiagnosed neurologic deficits .... There is no cure for CMT, but physical therapy, occupational therapy, braces and ...

  6. The controversy of varicella vaccination in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered...

  7. 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...

  8. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    Science.gov (United States)

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

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

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    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

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

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  11. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

  12. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available of the trial TropicALL study; Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with L...oprofylaxe in kinderen behandeld voor Acute lymfatische leukemie met laag-moleculair-gewicht heparine: een g...dition or disease under investigation E.1.1Medical condition(s) being investigated Acute lymphoblastic leukemia Acute... Medical condition or disease under investigation E.1.2Version 17.1 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute

  13. Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group.

    Science.gov (United States)

    Abromowitch, Minnie; Sposto, Richard; Perkins, Sherrie; Zwick, David; Siegel, Stuart; Finlay, Jonathan; Cairo, Mitchell S

    2008-10-01

    Pediatric lymphoblastic lymphoma (LL) has utilized treatment strategies similar to childhood acute lymphoblastic leukaemia (ALL) with prolonged maintenance chemotherapy. We report the results of a pilot study to estimate the feasibility, toxicity and efficacy of a 12-month aggressive multi-agent chemotherapy regimen in children and adolescents with advanced LL. Between July 1994 and June 1997, 85 eligible children and adolescents with advanced LL (Stage III/IV) were enrolled on this pilot study. Patients achieving a complete response following induction and consolidation received six cycles of maintenance chemotherapy for a total duration of 12 months. Grade III/IV toxicities included: hematological (80%), infections (20%), stomatitis and elevated transaminases, (29%). There were a total of 19 events, 13 relapses, two secondary acute myeloid leukaemia and four toxic deaths (5%). The 5-year event-free survival (EFS) and overall survival (OS) was 78 +/- 4.5% and 85 +/- 3.9%, respectively. Relapsed patients had a 5-year OS of only 33 +/- 14%. Multivariate analysis failed to demonstrate age, gender, lactate dehydrogenase level, presence of marrow and/or central nervous system disease to have independent prognostic value. These results suggest that this experimental approach is safe and results in similar outcomes as more prolonged childhood ALL regimens.

  14. Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell Transplant

    Science.gov (United States)

    2017-01-24

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; 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, Breakpoint Cluster Region-abl Translocation (BCR-ABL) Negative; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Gastrointestinal Complications; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Childhood Rhabdomyosarcoma; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia

  15. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Directory of Open Access Journals (Sweden)

    Laura Villarreal-Martínez

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recovery can also develop a few weeks after initiating steroid therapy. The etiologic relationship between the aplastic anemia features and the subsequent overt development of acute lymphoblastic leukemia has not been established. We describe the cases of two children who presented with severe infection and signs and symptoms of aplastic anemia confirmed by bone marrow aspirate and bone marrow biopsy that developed acute lymphoblastic leukemia thereafter. No specific therapy for aplastic anemia was administered, nevertheless a full spontaneous recovery was observed in both cases. Acute lymphoblastic leukemia was successfully treated with standard chemotherapy, both children remaining in complete remission 16 and 17 months after their initial aplastic anemia diagnosis.

  16. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.

    Science.gov (United States)

    Awasthi, Aradhana; Ayello, Janet; Van de Ven, Carmella; Elmacken, Mona; Sabulski, Anthony; Barth, Matthew J; Czuczman, Myron S; Islam, Humayun; Klein, Christian; Cairo, Mitchell S

    2015-12-01

    Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, (P = 0·001), Raji4RH 19·7 ± 2·2% vs. 7·9 ± 1·5% (P = 0·001) and U-698-M 47·3 ± 4·9% vs. 23·2 ± 0·5% (P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% (P = 0·001), Raji-4RH 40·0 ± 1·6% vs. 0·5 ± 1·1% (P = 0·001) and U-698-M 70·0 ± 1·6% vs. 45·5 ± 0·1% (P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0·05), Raji4RH (P = 0·02) and U698-M (P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL.

  17. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); 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(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 Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); 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 Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  18. ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins.

    Science.gov (United States)

    Ford, Anthony M; Greaves, Mel

    2017-01-01

    Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1).The natural history of childhood ALL is almost entirely clinically silent and is well advanced at the point of diagnosis. It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells.Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.

  19. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  20. [Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy].

    Science.gov (United States)

    Ribera, Jordi; Zamora, Lurdes; García, Olga; Hernández-Rivas, Jesús-María; Genescà, Eulàlia; Ribera, Josep-Maria

    2016-12-02

    Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  1. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  2. The mystery of electroencephalography in acute lymphoblastic leukemia.

    Science.gov (United States)

    Goldberg-Stern, Hadassa; Cohen, Rony; Pollak, Lea; Kivity, Sara; Eidlitz-Markus, Tal; Stark, Batya; Yaniv, Isaac; Shuper, Avinoam

    2011-04-01

    The aim of the study was to evaluate changes in electroencephalogram (EEG) recordings during the course of acute lymphoblastic leukemia (ALL) in children. The study group consisted of 48 children with ALL who underwent a total of 72 EEGs at various stages of the disease. The medical files were reviewed for pertinent clinical data, and the EEGs were evaluated for changes in brain activity. Abnormal background activity was noted in 52.2% of the EEGs done at 1-10 days of therapy, in 43.5% of those done at 10-60 days, and only 4.3% of those done at later stages (p=0.037). These findings, together with earlier reports, suggest that early-stage ALL, even before treatment, may be associated with excessive slow EEG activity, which improves over time. The EEG changes, by themselves, are not an indication of central nervous system leukemia or a predictor of later seizures or other central nervous system involvement.

  3. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, O G

    2012-08-01

    Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during frontline therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and result in hematologic remission rates exceeding 90%. Minimal residual disease levels are generally lower when TKIs are used in combination with chemotherapy rather than as monotherapy. Although outcome has improved substantially with TKI-based regimens compared with historic controls, allogeneic stem cell transplantation (SCT) in first remission provides the best chance of cure for the majority of patients eligible for SCT. Administration of imatinib after SCT further reduces molecular recurrence and is associated with greatly improved relapse-free and overall survival. The high relapse rate in non-transplanted patients is largely attributable to the emergence of leukemic clones with mutations in the tyrosine kinase domain of BCR-ABL. Ongoing studies with newer TKIs will determine whether these more potent agents are able to sustain remissions without SCT. Assessment of minimal residual disease has become an integral part of the management of Ph+ALL, as it has prognostic importance and is used to guide therapeutic intervention. Novel immunotherapeutic interventions and combinations of TKIs are currently being investigated in clinical trials and may further improve the prognosis of patients with Ph+ALL.

  4. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Directory of Open Access Journals (Sweden)

    Yadollah Zahedpasha

    2011-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.Case Presentation: This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didnt have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.Conclusion: The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.

  5. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia.

    Science.gov (United States)

    Raj, Trisha A Soosay; Smith, Amanda M; Moore, Andrew S

    2013-01-01

    Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.

  6. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

  7. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Stanković Tatjana

    2008-01-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.

  8. Infant acute lymphoblastic leukemia: a 20-year children's hospital experience.

    Science.gov (United States)

    Murray, Rebecca A F; Thom, Giddel; Gardner, Renee V; Craver, Randall D

    2008-01-01

    We reviewed our 20-year experience with infant acute lymphoblastic leukemia (ALL). Nine infants (4.2% of all ALL) were identified; all were < 6 months of age. White blood cell counts ranged from 42,000-1.6 million/microL, 6 of 8 had hepatosplenomegaly, and 6 of 9 (66.6%) had central nervous system disease. Of 7 with cytogenetic information, 6 (85.7%) had diploidy; the remaining child was 47, XY,+8,del(21)(q22). Four had the MLL-11q23 abnormality. All received chemotherapy. Four underwent stem cell transplantation. Survival was 67%, (15 months-21 years). Deaths occurred at 9 months, 15 months (graft vs. host), and 7 years (complications of small bowel transplantation). Only 1 undergoing stem cell transplantation died. There were no late recurrences or second malignancies. Despite extensive disease and age < 6 months at diagnosis (a poor prognostic feature), for ALL patients our 67% survival is at least as good as reported, although it is less favorable than childhood ALL.

  9. The genomic landscape of hypodiploid acute lymphoblastic leukemia.

    Science.gov (United States)

    Holmfeldt, Linda; Wei, Lei; Diaz-Flores, Ernesto; Walsh, Michael; Zhang, Jinghui; Ding, Li; Payne-Turner, Debbie; Churchman, Michelle; Andersson, Anna; Chen, Shann-Ching; McCastlain, Kelly; Becksfort, Jared; Ma, Jing; Wu, Gang; Patel, Samir N; Heatley, Susan L; Phillips, Letha A; Song, Guangchun; Easton, John; Parker, Matthew; Chen, Xiang; Rusch, Michael; Boggs, Kristy; Vadodaria, Bhavin; Hedlund, Erin; Drenberg, Christina; Baker, Sharyn; Pei, Deqing; Cheng, Cheng; Huether, Robert; Lu, Charles; Fulton, Robert S; Fulton, Lucinda L; Tabib, Yashodhan; Dooling, David J; Ochoa, Kerri; Minden, Mark; Lewis, Ian D; To, L Bik; Marlton, Paula; Roberts, Andrew W; Raca, Gordana; Stock, Wendy; Neale, Geoffrey; Drexler, Hans G; Dickins, Ross A; Ellison, David W; Shurtleff, Sheila A; Pui, Ching-Hon; Ribeiro, Raul C; Devidas, Meenakshi; Carroll, Andrew J; Heerema, Nyla A; Wood, Brent; Borowitz, Michael J; Gastier-Foster, Julie M; Raimondi, Susana C; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Hunger, Stephen P; Loh, Mignon L; Mullighan, Charles G

    2013-03-01

    The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.

  10. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  11. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

  12. TREATMENT OF ADOLESCENT AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

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    Josep-Maria Ribera

    2014-07-01

    Full Text Available The primary objective of this review was to update and discuss the current concepts andthe results of the treatment of acute lymphoblastic leukemia (ALL in adolescents and young adults(AYA. After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALLin the AYA population, the main retrospective comparative studies stating the superiority ofpediatric over adult-based protocols were reviewed. The most important prospective studies inyoung adults using pediatric inspired or pediatric unmodified protocols were also reviewedemphasizing their feasibility at least up to the age of 40 yr and their promising results, with eventfreesurvival rates of 60-65% or greater. Results of trials from pediatric groups have shown that theunfavourable prognosis of adolescents is no more adequate. The majority of the older adolescentswith ALL can be cured with risk-adjusted and minimal residual disease-guided intensivechemotherapy, without stem cell transplantation. However, some specific subgroups, which aremore frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like,deserve particular attention. In summary, the advances in treatment of ALL in adolescents havebeen translated to young adults, and that explains the significant improvement in survival of thesepatients in recent years.

  13. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

    The 50th anniversary of Seminars in Hematology coincides with the 50th of St. Jude Children’s Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset. PMID:23953334

  14. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

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    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  15. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  16. Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

    Science.gov (United States)

    2016-08-22

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

  17. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  18. Unravelling Pathobiological Molecular Mechanisms of T-Cell Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    R.D. Mendes (Rui Daniel)

    2016-01-01

    markdownabstractT-cell acute lymphoblastic leukemia (T-ALL) represents 10-15% of pediatric acute leukemias. Despite major therapeutic improvements due to treatment intensification and refined risk-adapted stratification during the past decade, ~30% of T-ALL cases relapse with very poor prognosis.

  19. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...

  20. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    NARCIS (Netherlands)

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  1. The use of optical microscope equipped with multispectral detector to distinguish different types of acute lymphoblastic leukemia

    Science.gov (United States)

    Pronichev, A. N.; Polyakov, E. V.; Tupitsyn, N. N.; Frenkel, M. A.; Mozhenkova, A. V.

    2017-01-01

    The article describes the use of a computer optical microscopy with multispectral camera to characterize the texture of blasts bone marrow of patients with different variants of acute lymphoblastic leukemia: B- and T- types. Specific characteristics of the chromatin of the nuclei of blasts for different types of acute lymphoblastic leukemia were obtained.

  2. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Feychting, Maria; Klaeboe, Lars

    2007-01-01

    We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort...

  3. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  4. Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study

    Directory of Open Access Journals (Sweden)

    Rashmi Kushwaha

    2014-01-01

    Full Text Available Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0, intratherapy (Day-14, and end of induction chemotherapy (Day-28 were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences Version 15.0 statistical Analysis Software. The values were represented in Number (% and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student ′t′ test, Level of significance P Results: Incidence of ALL-L1 (46.7% and ALL-L2 (53.3% was equal. ALL-L2 patients had poor survival.Day 0 (D-0 bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D′0′ were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D ′0′ parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day ′0′ to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20% at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction

  5. Unilateral Exudative Retinal Detachment as the Sole Presentation of Relapsing Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2012-06-01

    Full Text Available Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with the sole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblastic leukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferent pupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneously obtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation, and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecal chemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the need for enucleation.

  6. 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

  7. Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

    Science.gov (United States)

    Kasai-Yoshida, Emi; Ogihara, Masaaki; Ozawa, Miwa; Nozaki, Taiki; Morino, Michiharu; Manabe, Atsushi; Hosoya, Ryota

    2013-07-01

    Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

  8. [Alcaligenes xylosoxidans bacteremia in a patient with acute lymphoblastic leukemia].

    Science.gov (United States)

    Aydemir, Zeynep Alp; Ozdemir, Nihal; Celik, Nigar; Celkan, Tiraje

    2009-07-01

    Alcaligenes xylosoxidans which is an aerobic, non-fermentative gram-negative bacillus found in aqueous environments and human flora, can lead to opportunistic infections. It causes infections in elderly, immunocompromised patients, patients with chronic disorders or premature infants. In this report, a case of A. xylosoxidans bacteremia that developed in a child with acute lymphoblastic leukemia (ALL) was presented. Four-years-old male patient under ALL induction therapy was admitted with symptoms of lethargy, headache, somnolence, and fever (39 degrees C). Cerebrospinal fluid, blood, throat and urine cultures were taken from the patient and empirical treatment with sulbactam cefoperazon and amikacin was initiated. Blood cultures in BacT Alert 3D (Bio Merieux, France) revealed the growth of a gram-negative coccobacillus. The agent which was non-fermentative, indol and H2S negative, was identified as A. xylosoxidans by API 20 NE (Bio Merieux, France). Since fever continued under the current antibiotic treatment, the therapy was switched to imipenem (90 mg/kg 3x/day) and the patient's condition improved markedly after 24 hours. Disc diffusion susceptibility testing of the isolate revealed that it was resistant to ampicillin, cephalothin, cefuroxime, cefoxitin, cefotaxime, amikacin, netilmicin and gentamicin; susceptible to amoxicillin clavulanate, piperacillin tazobactam, seftazidime, cefepime, imipenem and ciprofloxacin. Following 14 days of imipenem therapy, the patient recovered and discharged from the hospital on routine follow-up. It is important to consider A. xylosoxidans as a possible causative agent particularly in the infections that develop in high risk patients at oncology, dialysis and neonatal intensive care units.

  9. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  10. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Campana, Dario; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Metzger, Monika L.; Bhojwani, Deepa; Inaba, Hiroto; Raimondi, Susana C.; Onciu, Mihaela; Howard, Scott C.; Leung, Wing; Downing, James R.; Evans, William E.; Relling, Mary V.

    2011-01-01

    Purpose The prognosis for older adolescents and young adults with acute lymphoblastic leukemia (ALL) has been historically much worse than that for younger patients. We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group. Patients and Methods Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents, were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first three studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL. Results The 89 older adolescents were significantly more likely to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease during or at the end of remission induction; they were less likely to have the t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies, the 44 older adolescents had significantly poorer event-free survival and overall survival than the 403 younger patients. This gap in prognosis was abolished in study XV: event-free survival rates at 5 years were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients; overall survival rates were 87.9% ± 5.1% versus 94.1% ± 1.2%, respectively. Conclusion Most older adolescents with ALL can be cured with risk-adjusted intensive chemotherapy without stem-cell transplantation. PMID:21172890

  11. 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.

  12. Meralgia Paresthetica as a Presentation of Acute Appendicitis in a Girl With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Nishimura, Miho; Kodama, Yuichi; Fukano, Reiji; Okamura, Jun; Ogaki, Kippei; Sakaguchi, Yoshihisa; Migita, Masahiro; Inagaki, Jiro

    2015-04-01

    A 7-year-old girl with Philadelphia chromosome-positive acute lymphoblastic leukemia developed recurrent fever and meralgia paresthetica (MP) during chemotherapy, which resolved after administration of antibiotics. Five months after the onset of these symptoms, enhanced computed tomography showed a periappendiceal abscess extending into the psoas muscle. The cause of her fever and MP was thought to be appendicitis, which probably developed during induction chemotherapy but did not result in typical abdominal pain. Patients with recurrent fever and MP should be evaluated by imaging examinations including computed tomography to search for appendicitis.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. UNUSUAL CLINICAL PRESENTATION OF RELAPSE IN PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA.

    Directory of Open Access Journals (Sweden)

    Vanya Slavcheva

    2015-04-01

    Full Text Available Acute lymphoblastic leukemia is a disease, which is more common in children. We report a clinical case of a patient aged 25. Thirty-two months before his last admission in Hematology clinic, acute pre- B lymphoblastic leukemia had been diagnosed and treated till March 2012. In September 2013 after bone marrow aspiration, flow cytometric analysis, trepan biopsy and biopsy of the kidney had been carried out, the patient was diagnosed with first late relapse, involving bone marrow and kidney. A second remission was achieved using Berlin- Frankfurt– Munster chemotherapy [BFM] and allogenic stem cell transplantation was performed.

  15. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

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

    OpenAIRE

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

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

  17. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    Science.gov (United States)

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  18. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-09-15

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

  19. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

    2016-06-01

    Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic

  20. TRESK potassium channel in human T lymphoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Miguel, Dénison Selene, E-mail: amurusk@hotmail.com [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); García-Dolores, Fernando, E-mail: garciaddf@yahoo.com [Department of Pathology, Institute of Forensic Sciences, Av. Niños Héroes 130, Col. Doctores, C.P. 06720 Mexico, DF (Mexico); Rosa Flores-Márquez, María, E-mail: mariafo31@yahoo.com.mx [National Medical Center of Occident (CMNO) IMSS, Belisario Dominguez 735, Col. Independencia Oriente, C.P. 44340 Guadalajara, Jalisco (Mexico); Delgado-Enciso, Iván [University of Colima, School of Medicine, Av. Universidad 333, Col. Las Viboras, C.P. 28040 Colima (Mexico); Pottosin, Igor, E-mail: pottosin@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); Dobrovinskaya, Oxana, E-mail: oxana@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico)

    2013-05-03

    Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K{sup +}) channel, encoded by KCNK18 gene, belongs to the double-pore domain K{sup +} channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K{sup +} channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

  1. Pediatric Burkitt lymphoma presenting as acute pancreatitis: MRI characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Amodio, John; Brodsky, Jennie E. [SUNY Downstate Medical Center, Department of Radiology, Brooklyn, NY (United States)

    2010-05-15

    Acute pancreatitis is a rare initial presentation of non-Hodgkin lymphoma with few reported cases described in older adults and even fewer in children. MRI features of Burkitt lymphoma of the pancreas are sparse in the radiologic literature. We present a 6-year-old boy who presented with pancreatitis and obstructive jaundice, which was the result of Burkitt lymphoma of the pancreas. The imaging findings of pancreatic involvement of Burkitt lymphoma on MRI are discussed and the contributory role of the radiologist in guiding the appropriate clinical work-up of this disease is highlighted. (orig.)

  2. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Schrappe, Martin; Hunger, Stephen P.; Pui, Ching-Hon; Saha, Vaskar; Gaynon, Paul S.; Baruchel, André; Conter, Valentino; Otten, Jacques; Ohara, Akira; Versluys, Anne Birgitta; Escherich, Gabriele; Heyman, Mats; Silverman, Lewis B.; Horibe, Keizo; Mann, Georg; Camitta, Bruce M.; Harbott, Jochen; Riehm, Hansjörg; Richards, Sue; Devidas, Meenakshi; Zimmermann, Martin

    2012-01-01

    BACKGROUND Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. CONCLUSIONS Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche

  3. Inter-Platform comparability of microarrays in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mintz Michelle

    2004-09-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS rates improving from 80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21[TEL-AML1], t(4;11[MLL-AF4], t(9;22[BCR-ABL], and t(1;19[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. Results We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors

  4. Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: a case report

    Directory of Open Access Journals (Sweden)

    Awasum Michael

    2011-07-01

    Full Text Available Abstract Introduction Acute leukemias very rarely present with jaundice. Herein we report a case of precursor B-cell acute lymphoblastic leukemia that presented with jaundice in an adult. Case presentation A 44-year-old Hispanic man presented with right upper quadrant abdominal pain and jaundice. His initial blood work revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50% of the total. His imaging studies were unremarkable except for hepatomegaly. All blood screening tests for various hepatocellular etiologies were normal. A diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy. The patient was treated with a hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. Conclusion Acute lymphoblastic leukemia should be one of the differential diagnoses that should be considered when initial work-up for jaundice is inconclusive. Some cases of acute lymphoblastic leukemia have been reported in both adults and children to have presented with the initial manifestation of jaundice, but only a few had no radiographic evidence of biliary obstruction. Such presentation can pose a serious diagnostic dilemma for clinicians. This manuscript attempts to highlight it. Moreover, we believe that if acute lymphoblastic leukemia presentations similar to this case continue to be reported in adults or children, a specific immunophenotypic expression and cytogenetic abnormality may be found to be associated with hepatic infiltration by leukemia. This may substantially contribute to the further understanding of the pathophysiology of this hematologic disease.

  5. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  6. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  7. Fatal Aspergillus rhinosinusitis during induction chemotherapy in a child with acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Flier, M. van der; Borgstein, J.A.; Lequin, M.H.; Sluis, I.M. van der

    2009-01-01

    Invasive fungal infections are a major problem in patients treated for hematologic malignancies. We report a 3-year-old girl who suffered from febrile neutropenia during induction therapy for acute lymphoblastic leukemia. Initial chest computed tomography revealed no evidence of intrapulmonary funga

  8. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  9. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

    Science.gov (United States)

    Mainor, Candace B; Duffy, Alison P; Atkins, Kristin L; Kimball, Amy S; Baer, Maria R

    2016-04-01

    BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.

  10. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  11. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.A.; Schoemaker, M.M.; Göeken, L.N.H.; Bökkerink, J.P.M.; Kamps, W.A.

    2001-01-01

    Background. Children treated for acute lymphoblastic leukemia (ALL) often complain about handwriting problems. Procedure. Using a computerized writing task, we have prospectively studied the processes necessary for the production of handwriting movements in I I children (5-12 years old) during treat

  12. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  13. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    DEFF Research Database (Denmark)

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  14. 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...

  15. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment

    NARCIS (Netherlands)

    A. Holleman (Amy); C. Cheng (Cheng); C.H. Pui (Ching-Hon); W.E. Evans (William); M.V. Relling (Mary); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); M.H. Cheok (Meyling); M.L. den Boer (Monique); W. Yang; A.J. Veerman; K.M. Kazemier (Karin); D. Pei (Deqing)

    2004-01-01

    textabstractBACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173

  16. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  17. Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Loennerholm, Gudmar; Frost, Britt-Marie; Abrahamsson, Jonas; Behrendtz, Mikael; Castor, Anders; Forestier, Erik; Heyman, Mats; Uges, Donald R. A.; de Graaf, Siebold S. N.

    2008-01-01

    Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We he

  18. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  19. Erroneous exchange of asparaginase forms in the treatment of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Cheung, K.C.; Bemt, P.M. van den; Torringa, M.L.; Tamminga, R.Y.; Pieters, R.; Smet, P.A. de

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  20. Erroneous Exchange of Asparaginase Forms in the Treatment of Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Cheung, Ka-Chun; van den Bemt, Patricia M. L. A.; Torringa, Maarten L. J.; Tamminga, Rienk Y. J.; Pieters, Rob; de Smet, Peter A. G. M.

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  1. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

  2. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age develop

  3. The significance of change of Th22 cells in patients with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    刘立民

    2013-01-01

    Objective To investigate the proportion of Th22 cells in peripheral blood of patients with acute lympho-blastic leukemia(ALL) and evaluate its significance.Methods The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy(group 1),

  4. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    2009-01-01

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with inter

  5. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; Zhang, Jinghui; Wei, L.; Wu, G.; Rusch, M.; Nagahawatte, P.; Ma, J; Chen, S.C.; Song, G.; Cheng, J.; Meyers, P.; Bhojwani, D.; Jhanwar, S.; Maslak, P.; Fleisher, M.; Littman, J.; Offit, L.; Rau-Murthy, R.; Fleischut, M.H.; Corines, M.; Murali, R.; Gao, X.; Manschreck, C.; Kitzing, T.; Murty, V.V.; Raimondi, S.C.; Kuiper, R.P.; Simons, A.; Schiffman, J.D.; Onel, K.; Plon, S.E.; Wheeler, D.A.; Ritter, D.; Ziegler, D.S.; Tucker, K.; Sutton, R.; Chenevix-Trench, G.; Li, J.; Huntsman, D.G.; Hansford, S.; Senz, J.; Walsh, T.; Lee, M. van der; Hahn, C.N.; Roberts, K.G.; King, M.C.; Lo, S.M.; Levine, R.L.; Viale, A.; Socci, N.D.; Nathanson, K.L.; Scott, H.S.; Daly, M.; Lipkin, S.M.; Lowe, S.W.; Downing, J.R.; Altshuler, D.; Sandlund, J.T.; Horwitz, M.S.; Mullighan, C.G.; Offit, K.

    2013-01-01

    Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly1

  6. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery,

  7. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  8. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse.

  9. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    NARCIS (Netherlands)

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  10. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, SLA; de Bont, ESJM; Boezen, M; vander Kolk, DM; Daenen, SMJG; Faber, KN; Kamps, WA; de Vries, EGE; Vellenga, E

    2005-01-01

    PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the exp

  11. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    D. Schotte (Diana); R.X. de Menezes (Renee); F. Akbari Moqadam (Farhad); L.M. Khankahdani (Leila Mohammadi); E.A.M. Lange-Turenhout (Ellen); C. Chen (Caifu); R. Pieters (Rob); M.L. den Boer (Monique)

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression

  12. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

  13. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties

    NARCIS (Netherlands)

    le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Roettgers, Silja; Schrauder, Andre; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Juergens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

    We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34

  14. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours

  15. Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Jansen, Nathalie C. A. J.; Kingma, Annette; Schuitema, Arnout; Bouma, Anke; Veerman, Anjo J. P.; Kamps, Willem A.

    2008-01-01

    Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and syst

  16. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  17. Glioblastoma multiforme in a child with acute lymphoblastic leukemia: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Shah Kirit

    2004-07-01

    Full Text Available An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.

  18. Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R.D. van Beek (Robert Diederik); S.M.P.F. de Muinck Keizer-Schrama (Sabine); A.G. Uitterlinden (André); W.C.J. Hop (Wim); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2010-01-01

    textabstractBackground This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2

  19. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

  20. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; te Winkel, Mariel L.; de Groot-Kruseman, Hester A.; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan; Bruin, Marrie C. A.; van der Sluis, Inge M.; Bresters, Dorien; Lequin, Maarten H.; Roos, Jan C.; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence e

  1. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bis

  2. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    2010-01-01

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a chi

  3. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  4. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies

    NARCIS (Netherlands)

    J.J.M. van Dongen (Jacques); V.H.J. van der Velden (Vincent); M. Brüggemann (Monika); A. Orfao (Alberto)

    2015-01-01

    textabstractMonitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group

  5. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age

  6. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours o

  7. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  8. 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...

  9. 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...

  10. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L.; Wehner, Peder S.

    2017-01-01

    with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C...

  11. 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...

  12. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a

  13. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Wahlberg, Per

    2013-01-01

    BACKGROUND: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic...

  14. Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    ReindersMesselink, HA; Schoemaker, MM; Hofte, M; Goeken, LNH; Kingma, A; vandenBriel, MM; Kamps, WA

    1996-01-01

    Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Cross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We

  15. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  16. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Zachariadis, Vasilios

    2015-01-01

    BACKGROUND: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA...

  17. 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...

  18. Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schüz, J; Grell, K; Kinsey, S

    2012-01-01

    A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada...

  19. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.

    Science.gov (United States)

    Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-07-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further. Copyright© Ferrata Storti Foundation.

  20. Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

    Directory of Open Access Journals (Sweden)

    Parra-Baltazar, Isabel Mónica

    2016-10-01

    Full Text Available Down syndrome (DS or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL. We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

  1. Novel cryptic chromosomal rearrangements detected in acute lymphoblastic leukemia detected by application of new multicolor fluorescent in situ hybridization approaches

    NARCIS (Netherlands)

    Karst, C; Gross, M; Haase, D; Wedding, U; Hoffken, K; Liehr, T; Mkrtchyan, H

    2006-01-01

    Routine cytogenetic analysis provides important information on diagnostic and prognostic relevance for hematological malignancies. However, it is often difficult to obtain good karyotypes, especially of cells from cases with acute lymphoblastic leukemia (ALL) because of poor morphology and spreading

  2. Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Winkel, M.L. te; Pieters, R.; Hop, W.C.J.; Groot-Kruseman, H.A. de; Lequin, M.H.; Sluis, I.M. van der; Bokkerink, J.P.M.; Leeuw, J.A. de; Bruin, M.C.; Egeler, R.M.; Veerman, A.J.P.; Heuvel-Eibrink, M.M. van den

    2011-01-01

    PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with

  3. Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Winkel, Mariel L. Te; Pieters, Rob; Hop, Wim C. J.; de Groot-Kruseman, Hester A.; Lequin, Maarten H.; van der Sluis, Inge M.; Bokkerink, Jos P. M.; Leeuw, Jan A.; Bruin, Marrie C. A.; Egeler, R. Maarten; Veerman, Anjo J. P.; van den Heuvel-Eibrink, Marry M.

    2011-01-01

    Purpose We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). Patients and Methods Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with th

  4. No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only : A prospective longitudinal study

    NARCIS (Netherlands)

    Kingma, A; Van Dommelen, RI; Mooyaart, EL; Wilmink, JT; Deelman, BG; Kamps, WA

    2002-01-01

    Purpose: To study. using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only. Patients and Methods: Twenty consecutive patients underwent

  5. 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...

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

    DEFF Research Database (Denmark)

    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...

  7. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects...

  8. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R; Liu, Wei; Glass, John O; Ji, Qing; Ogg, Robert J; Sabin, Noah D; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Reddick, Wilburn E

    2014-11-01

    Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in

  9. Disseminated lymphoma presenting as acute thigh pain and renal failure.

    LENUS (Irish Health Repository)

    Brown, Catherine

    2009-01-01

    A 66-year-old diabetic man presented with severe right thigh swelling and pain together with acute renal failure. At autopsy, this was found to be due to disseminated high grade B cell lymphoma invading the psoas muscle and multiple organs, including the kidneys. The unique presentation of this case emphasizes the need for increased awareness of the variety of ways in which lymphoma can manifest itself.

  10. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    Science.gov (United States)

    2015-10-30

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  13. Unusual cytochemical reactivity for toluidine blue in granular acute lymphoblastic leukemia: a report of two rare cases

    Directory of Open Access Journals (Sweden)

    Rishu Agarwal

    2010-03-01

    Full Text Available Azurophilic granulation of blasts is a feature of acute myeloid leukemia (AML. Granular acute lymphoblastic leukemia (ALL may mimic AML due to the presence of cytoplasmic granules in lymphoblasts, but cytochemistry and immunophenotyping are helpful in making the correct diagnosis. Toluidine blue (TB is a metachromatic dye, which stains basophils and myeloid blasts that exhibit basophilic differentiation. Reactivity for TB has not been described in lymphoblasts. We herein report two cases of granular ALL with blasts exhibiting reactivity for TB that caused diagnostic dilemma. Immunophenotyping and cytogenetic studies were helpful in making a correct diagnosis. This report of two rare case highlight the reactivity of lymphoblasts with TB not hitherto described and the importance of a detailed diagnostic work-up in acute leukemia.

  14. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal...... antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute...

  15. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  16. The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32.

    Directory of Open Access Journals (Sweden)

    E J Dettman

    Full Text Available BACKGROUND: AKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of lymphoid and myeloid malignancies. In these tumors, the hematopoietic insertion of an active AKV murine leukemia virus (MuLV is associated with the onset of disease. Common sites of retroviral insertion (CIS identify genes causally associated with the development or initiation of lymphoma. METHODOLOGY: In the present study, we analyzed a previously uncharacterized CIS, Ecotropic Viral Integration Site 32 (Evi32, which is located on mouse chromosome 1. We analyzed candidate genes in the region to identify those involved in Evi32 mediated oncogenesis. RESULTS: Here we show that proviral insertion at Evi32 correlates with significant overexpression of a putative transcription factor, PR-domain containing 14 (Prdm14. Tumors with insertions at Evi32 are consistently lymphoid in nature. Prdm14 is normally expressed early in embryonic development with the highest expression in undifferentiated embryonic stem (ES cells. This study implicates Prdm14 as a proto-oncogene involved in lymphoblastic lymphoma formation.

  17. SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

    Directory of Open Access Journals (Sweden)

    Zaborski Margarete

    2009-01-01

    Full Text Available Abstract Background SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9(q34.11q34.13 has recently been described in T-cell acute lymphoblastic leukemia (T-ALL and in one case of acute myeloid leukemia (AML. The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene. Results Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Iβ-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Iα-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH and array-based copy number analysis were both consistent with del(9(q34.11q34.13 as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein. Conclusion Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

  18. 1) Acute Lymphoblastic Leukemia 2) Lymphoblastic Lymphoma | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available a asparaginasa de E. coli en adultos jóvenes con leucemia linfoblástica aguda o ...pacientes adultos jóvenes con diagnóstico de leucemia linfoblástica aguda (LLA) o linfoma linfoblástico (LL)

  19. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    OpenAIRE

    Idalia Garza-Veloz; Margarita L. Martinez-Fierro; Jose Carlos Jaime-Perez; Karol Carrillo-Sanchez; Maria Guadalupe Ramos-Del Hoyo; Angel Lugo-Trampe; Augusto Rojas-Martinez; Cesar Homero Gutierrez-Aguirre; Oscar Gonzalez-Llano; Rosario Salazar-Riojas; Alfredo Hidalgo-Miranda; David Gomez-Almaguer; Rocio Ortiz-Lopez

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by...

  20. Guillain-Barré syndrome in a child with acute lymphoblastic leukemia.

    Science.gov (United States)

    Aral, Y Z; Gursel, T; Ozturk, G; Serdaroglu, A

    2001-01-01

    A 4-year-old boy with acute lymphoblastic leukemia receiving maintenance treatment developed quadriparesis, facial palsy, difficulty in swallowing, and hypertension following a respiratory infection and candida septicemia. Examination of the cerebrospinal fluid was normal initially but later showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. Complete recovery occurred after treatment with intravenous immunoglobulin. Differential diagnosis of Guillain-Barré syndrome from vincristine toxicity in patients with leukemia and possible association with the infections are discussed.

  1. 6-Thioguanine Induces Mitochondrial Dysfunction and Oxidative DNA Damage in Acute Lymphoblastic Leukemia Cells*

    OpenAIRE

    Zhang, Fan; Fu, Lijuan; Wang, Yinsheng

    2013-01-01

    Thiopurines are among the most successful chemotherapeutic agents used for treating various human diseases, including acute lymphoblastic leukemia and chronic inflammation. Although metabolic conversion and the subsequent incorporation of 6-thioguanine (SG) nucleotides into nucleic acids are considered important for allowing the thiopurine drugs to induce their cytotoxic effects, alternative mechanisms may also exist. We hypothesized that an unbiased analysis of SG-induced perturbation of the...

  2. Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Emine Guven Maiorov; Ozlem Keskin; Ozden Hatirnaz Ng; Ugur Ozbek; Attila Gursoy

    2013-01-01

    Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 210253, 20 pages http://dx.doi.org/10.1155/2013/210253 Research Article Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia Emine Guven Maiorov,1 Ozlem Keskin,1 Ozden Hatirnaz Ng,2 Ugur Ozbek,2 and Attila Gursoy1 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc¸ University, Rumelifeneri Yolu, Sariyer, 34450 Istanbu...

  3. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  4. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    OpenAIRE

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala,; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry a...

  5. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    den Hoed, Marissa A H; Pluijm, Saskia M F; te Winkel, Mariël L; de Groot-Kruseman, Hester A; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan A; Bruin, Marrie C A; van der Sluis, Inge M; Bresters, Dorien; Lequin, Maarten H; Roos, Jan C; Veerman, Anjo J P; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2015-12-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Posteonecrosis: -1.73 versus without osteonecrosis: -0.57, Posteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, Posteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

  6. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter; Graux, Carlos; Cauwelier, Barbara; Lambert, Frederic; Mentens, Nicole; Beverloo, H Berna; Pieters, Rob; Speleman, Frank; Odero, Maria D; Bauters, Marijke; Froyen, Guy; Marynen, Peter; Vandenberghe, Peter; Wlodarska, Iwona; Meijerink, Jules P P; Cools, Jan

    2007-05-01

    We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

  7. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    OpenAIRE

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintena...

  8. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Rosalyn P. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Kaste, Sue C. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Department of Radiology, University of Tennessee, College of Medicine, Memphis, Tennessee (United States)

    2004-05-01

    Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family. (orig.)

  9. 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) that alters T cell specificity and function to recognize tumor antigens.

  10. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

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

    Science.gov (United States)

    For acute lymphoblastic leukemia (ALL), the 5-year survival rate rose from 60% to about 90% for children younger than 15 years and from 28% to about 75% for adolescents aged 15–19 years between 1975 and 2010. Get information about risk factors, signs, diagnosis, genomics, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

  12. The molecular genetic makeup of acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention.

  13. Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity

    Science.gov (United States)

    Thathia, Shabnam H.; Ferguson, Stuart; Gautrey, Hannah E.; van Otterdijk, Sanne D.; Hili, Michela; Rand, Vikki; Moorman, Anthony V.; Meyer, Stefan; Brown, Robert; Strathdee, Gordon

    2012-01-01

    Background Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. Design and Methods TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. Results We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). Conclusions This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy. PMID:22058208

  14. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    OpenAIRE

    Jacob JA; Salmani JMM; Chen B

    2016-01-01

    Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Abstract: Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs...

  15. Successful acute lymphoblastic leukemia-type therapy in two children with mixed-phenotype acute leukemia.

    Science.gov (United States)

    Otsubo, Keisuke; Yabe, Miharu; Yabe, Hiromasa; Fukumura, Akiko; Morimoto, Tsuyoshi; Kato, Masahiko; Mochizuki, Hiroyuki

    2016-10-01

    Mixed-phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B-lymphoid markers. Patient 2 was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) using EGIL criteria. According to the 2008 WHO classification, however, patient 2 was diagnosed with overt MPAL positive for CD3, T-lymphoid markers and MPO. We chose an ALL-type therapy consisting of both lymphoid- and myeloid-directed agents; these patients have maintained complete remission following treatment. Further information on pediatric MPAL is needed to establish an appropriate therapeutic strategy including stem cell transplantation for this rare condition. © 2016 Japan Pediatric Society.

  16. Myeloid Sarcoma Presenting with Leukemoid Reaction in a Child Treated for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Aylin Canbolat Ayhan

    2014-01-01

    Full Text Available Background. Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia. Case Presentation. A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm3. FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma. Conclusion. Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.

  17. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available INTRODUCTION: Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown. OBJECTIVE: To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. METHODOLOGY: A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content. RESULTS: Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6. CONCLUSION: The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

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

    Science.gov (United States)

    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.

  19. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

    2009-11-15

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

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

    Science.gov (United States)

    2016-09-29

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

  1. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  2. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  3. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  4. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; 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

  5. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: An iBFM-SG study

    NARCIS (Netherlands)

    E. Forestier (Erik); S. Izraeli (Shai); H.B. Beverloo (Berna); O.A. Haas (Oskar); A. Pession (Andrea); K. Michalová (Kyra); B. Stark (Batia); C.J. Harrison (Christine); A. Teigler-Schlegel; B. Johansson (Bert)

    2008-01-01

    textabstractChildren with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALLs and

  6. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas;

    2013-01-01

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.......The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined....

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma.

    Directory of Open Access Journals (Sweden)

    Monique F M A Smeets

    Full Text Available The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL. Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways.

  10. Relationship between the general condition of acute lymphoblastic leukemia patients with remission rate and convulsion as an adverse effect chemotherapy

    Directory of Open Access Journals (Sweden)

    Rusdi Andid

    2017-02-01

    Full Text Available A retrospective study on the relationship between the general condition of acute lymphoblastic leukemia patients with remission rale and convulsion as an adverse effect of chemotherapy was conducted in leukemia patients of the hematology-oncology subdivision, Departmenl of Child Health, Medical School, University of North Sumatra, Medan. Of 114 children with acute lymphoblastic leukemia, 81 (71.05% received chemotherapy, 31 patients among them was in good general condition. Remission rate of the 31 patients was 80.6% (25 children. Whereas in the remaining 50 patients, the remission rate among them was 84% (42 patients. There was no significant relationship between their general condition to the recurrence rate of acute lymphoblastic leukemia patients who had been administered chemotherapy during induction phase. Convulsion was found In 2 cases, due to CNS leukemia.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

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

  13. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

    Directory of Open Access Journals (Sweden)

    Lee KJ

    2016-08-01

    Full Text Available Kum Ja Lee,1 Vivian Chow,1 Ashley Weissman,2 Sunil Tulpule,3 Ibrahim Aldoss,4 Mojtaba Akhtari5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, University of Southern California Norris Cancer Hospital, Los Angeles, CA, 3Department of Medicine, Raritan Bay Medical Center, Perth Amboy, NJ, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 5Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Abstract: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug

  14. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

    2016-08-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. Copyright© Ferrata Storti Foundation.

  15. Testicular involvement in acute lymphoblastic leukemia. Consequences of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, R.; Czernichow, P.; Rappaport, R.; Schaison, G.

    1986-06-05

    Acute lymphoblastic leukemia has a higher mortality rate in boys as a result of possible testicular involvement; indeed, the testicle is the site of initial relapse in 6% of cases and is involved in 15% of all cases. Clinical diagnosis of testicular involvement is usually readily established. Treatment is delivery of 24 grays to both testicles and intensification of chemotherapy. In children who recover from their leukemia, this irradiation produces not only destruction of germ cells but also endocrine impairment which should be looked for and treated; replacement therapy with slow-action testosterone will be combined with the other hormonal treatments which pituitary deficiencies secondary to cranial irradiation may require.

  16. [ICO-35 monoclonal antibodies to the antigen of acute lymphoblastic leukemia].

    Science.gov (United States)

    Baryshnikov, A Iu; Tupitsyn, N N; Korotkova, O V; Kadagidze, Z G; Dostot, E; Shmidt, M; Boumsell, L

    1989-01-01

    ICO-35 monoclonal antibodies (Mabs) were produced following BALB/c mouse immunization with peripheral blood cells from a patient with lymphoid type of chronic myeloid leukemia in blast crisis (SML BC) ICO-35. Mabs detect antigen on CD10-positive cells from patients with acute lymphoblastic leukemia, CML BC, CD10-positive cells of Reh line and are not bound to other cells. Comparative studies of reactivity of ICO-35 and K 503 Mabs to CD10 antigen revealed their similarity. However, in contrast to K503 ICO-35 Mabs do not react with granulocytes.

  17. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  18. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    OpenAIRE

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K.

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. Th...

  19. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  20. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Henriksen, Louise Tram; Harila-Saari, Arja; Ruud, Ellen;

    2015-01-01

    BACKGROUND: L-Asparaginase is an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL). The use of L-asparaginase may be limited by serious adverse events of which allergy is the most frequent. The objective of this study was to describe the clinical aspects of PEG......-asparaginase allergy in children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol. PROCEDURE: Children (1-17 years) enrolled in the NOPHO ALL2008 protocol between July 2008 and August 2011, who developed PEG-asparaginase allergy were identified through the NOPHO...

  1. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances.

    Science.gov (United States)

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  2. FACIAL PALSY AS FIRST PRESENTATION OF ACUTE LYMPHOBLASTIC LEUKEMIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    S. Inaloo

    2008-11-01

    Full Text Available ObjectiveFacial paralysis in children is very often idiopathic and isolated facial nerve palsy, resulting from leukemic infiltration is a rare occurrence. Here we present the case of a 14 year-old boy with acute lymphobastic leukemia, who first presented with isolated right side peripheral facial nerve paralysis and was initially diagnosed with Bell's palsy.ConclusionThe presence of Bell's palsy in young children requires a complete evaluation, keeping in mind the possibility of leptomeningeal disease.Key words: Lymphoblastic Leukemia, Facial nerve palsy, Children.

  3. Bacillus cereus catheter related bloodstream infection in a patient with acute lymphoblastic leukemia.

    Science.gov (United States)

    Gurler, N; Oksuz, L; Muftuoglu, M; Sargin, Fd; Besisik, Sk

    2012-01-01

    Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related bloodstream infections. Significant catheter-related bloodstream infections (CRBSI) caused by Bacillus spp. are mainly due to B. cereus and have been predominantly reported in immunocompromised hosts. Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B. cereus in a patient with acute lymphoblast c leukemia (ALL) in Istanbul Medical Faculty was presented.

  4. Vincristine-induced peripheral neuropathy in a neonate with congenital acute lymphoblastic leukemia.

    Science.gov (United States)

    Baker, Steven K; Lipson, David M

    2010-04-01

    We report the case of a 46-day-old boy with a fulminant vincristine-induced peripheral neuropathy after treatment for congenital acute lymphoblastic leukemia. Flaccid paralysis developed at the end of the first phase of induction, requiring intubation and ventilation for 51 days. Treatment was initiated with levocarnitine, N-acetylcysteine, and pyridoxine and progressive reversal of the neuropathy occurred over the next 4 months. Potential differences in pathogenesis and presentation of vincristine neurotoxicity and Guillian-Barre syndrome in the neonate are discussed.

  5. 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 lymphoblastic...... 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...... resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients....

  6. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

  7. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  8. Acute lymphoblastic leukemia in children with associated genetic conditions other than Down's syndrome. The AIEOP experience.

    Science.gov (United States)

    Ziino, Ottavio; Rondelli, Roberto; Micalizzi, Concetta; Luciani, Matteo; Conter, Valentino; Aricò, Maurizio

    2006-01-01

    We retrospectively reviewed the databases of seven studies on acute lymphoblastic leukemia (ALL) by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) to identify patients with associated genetic disease, other than Down's syndrome. Forty-two patients were reported to have associated genetic conditions that included beta-thalassemia (n=10), ataxia-telangiectasia (n=5), neurofibromatosis (n=3), Sotos syndrome (n=2) and other individual conditions. Patients with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency of adverse events.

  9. [Nephrotoxicity evaluation of cytostatic agents in children with acute lymphoblastic leukemia].

    Science.gov (United States)

    Tomaszewska, B; Zoch-Zwierz, W M

    1995-11-01

    Urinary excretion of the markers of tubular nephrotoxicity, total NAG and isoenzymes A and B and B-2-M, were evaluated in urine of 21 children with acute lymphoblastic leukaemia after the first injection of cytostatic administrated according to the BFM scheme: VCR + Rub, L-aspa, CY, Ara-C. Every administrated drug caused temporary elevation in urinary excretion of total NAG and isoenzyme B and B-2-M. GFR was unchanged. These results point to nephrotoxicity of cytostatics. Peak total NAG, isoenzyme B and B-2-M excretion was observed on the third day after L-aspa and Ara-C injection.

  10. [Ribonuclease binase induces death in T-cell acute lymphoblastic leukemia cells by apoptosis].

    Science.gov (United States)

    Burnysheva, K M; Petrushanko, I Yu; Spirin, P V; Prassolov, V S; Makarov, A A; Mitkevich, V A

    2016-01-01

    Bacterial ribonuclease binase is a potential anticancer agent. In the present study, we have determined the toxic effect of binase towards cell lines of T-cell acute lymphoblastic leukemia Jurkat and CEMss. We have shown that binase induces apoptosis in these cells. At the same time, binase does not cause toxic effects in leukocytes of healthy donors, which suggests that binase activity towards leukemic cells is selective. We have found that the treatment of cancer cells with binase leads to a reduction in reactive oxygen species and transcription factor NFκB levels, and demonstrated that these effects are a common feature of the action of RNases on cancer cells.

  11. 来自澳大利亚的经验:成人急性淋巴细胞白血病用Hyper-CVAD治疗的结果%Outcome of Treatment of Adult Acute Lymphoblastic Leukemia with Hyperfractionated Cyclophosphamide,Doxorubicin, Vincristine, Dexamethasone/Methotrexate, Cytarabine: Results from An Australian Population

    Institute of Scientific and Technical Information of China (English)

    李军民; 陆泽生

    2011-01-01

    1 文献来源Morris K,Weston H,Mollee P,et al.Outcome of treatment of adult acute lymphoblastic leukemia with hypeffractionated Cyclophosphamide,Doxorubicin,Vincristine,Dexamethasone/Methotrexate,Cytarabine:Results from an Australian population [J].Leuk Lymphoma,2011,52( 1 ):85-91.2 证据水平2b.%Department of Hematology, Ruijin Hospital, Shanghai Jiaotong Unverisity School of Medicine, Shanghai Institute of Hematology, Shanghai 200025, China

  12. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

    Directory of Open Access Journals (Sweden)

    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  13. Burkitt's lymphoma causing acute pancreatitis in a child

    Directory of Open Access Journals (Sweden)

    Muhammed Akıl

    2013-01-01

    Full Text Available A 8-year-old boy admitted with abdominal pain, fever and vomiting for the previous 10 days. Sensitivity was detected in the epigastric area. There was not defense and rebond. Aspartate aminotransferase was 106 U/L, alanine aminotransferase 25 U/L, alkaline phosphatase 311 U/L, blood amylase level 748 U/L, blood lipase level 391 U/L. In thoracic CT, soft tissue with smooth contours measuring 32 mm×28 mm was identified in the posterior mediastinum. Bone marrow aspiration biopsy was normal. A mass specimen obtained from the duodenum endoscopic biopsy. This specimen was diffuse staining by leukocyte common antigen, CD10 and CD20. The patient was diagnosed with acute pancreatitis associated with stage 3 duodenal Burkitt's lymphoma. Modified LMB-98 was initiated. Burkitt's lymphoma may rarely cause acute pancreatitis.

  14. A case of lymphoma presented with acute renal failure

    Directory of Open Access Journals (Sweden)

    Mustafa Yaprak

    2017-03-01

    Full Text Available Acute renal failure (ARF in patients with malignancy occurs due to causes such as prerenal, renal and post renal as in normal population. Tumor infiltration of kidneys is usually uncommon. However, renal function may be impaired in fast-growing hematological malignancies such as acute leukemia or lymphoma, depending on tumor involvement. Herein, we presented a case of ARF and later diagnosed as B-cell Non-Hodgkin's lymphoma. 54-year-old male patient was admitted due to ARF. Although development of ARF due to tumor infiltration is rare, in cases who did not have risk factors for development of ARF, leukemic or lymphomatous infiltration should be considered. [Cukurova Med J 2017; 42(1.000: 168-171

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

    Science.gov (United States)

    2017-09-14

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

  16. Clinical reversible myelopathy in T-cell lymphoblastic lymphoma treated with nelarabine and radiotherapy: report of a case and review of literature of an increasing complication.

    Science.gov (United States)

    Tisi, Maria Chiara; Ausoni, Giuseppe; Vita, Maria Gabriella; Tartaglione, Tommaso; Balducci, Mario; Laurenti, Luca; Chiusolo, Patrizia; Hohaus, Stefan; Sica, Simona

    2015-01-01

    Eleven cases of neurological defects in T-ALL patients treated with nelarabine have been described in the last 4 years, seven of these after stem cell transplantation (SCT) for T Lymphoblastic Lymphoma (T-LBL). Most of these patients had an unfavorable outcome or irreversible neurological damage. We now report the case of a 41-year-old woman suffering from T-LBL who presented with severe, but reversible myelopathy after receiving nelarabine-based treatment and mediastinal radiotherapy, and we provide a review of the literature on the topic.

  17. ClinicaI Reversible Myelopathy in T-Cell Lymphoblastic Lymphoma Treated with Nelarabine and Radiotherapy: Report of a Case and Review of Literature of an Increasing Complication

    Directory of Open Access Journals (Sweden)

    Maria Chiara Tisi

    2015-02-01

    Full Text Available To date, eleven cases of irreversible neurological defects in T- ALL patients treated with nelarabine have been described in the last 4 years, seven of these after stem cell transplantation (SCT for T Lymphoblastic Lymphoma (T-LBL. Most of patients had an unfavorable outcome or irreversible damage. We report the case of a 41-year-old woman suffering from T-LBL who presented severe but reversible myelopathy after nelarabine based treatment and mediastinum radiotherapy, and we perform a review of literature.

  18. Splenic artery pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase

    DEFF Research Database (Denmark)

    Larsen, Cæcilie Crawley; Laursen, Christian B; Dalby, Kasper;

    2014-01-01

    Acute pancreatitis is a rare phenomenon in children but its incidence seems to be increasing. In children, it is generally caused due to systemic illness, biliary disease, trauma, idiopathy and side effects of medicines like L-aspariginase. Acute pancreatitis is difficult to diagnose in children...... pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase. He presented with fever, irritability and pain in his left groin region....

  19. [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia cell line Jurkat].

    Science.gov (United States)

    Wang, Chi-Juan; Xu, Hua; Zhang, Hai-Rui; Wang, Jian; Lin, Ya-Ni; Pang, Tian-Xiang; Li, Qing-Hua

    2014-08-01

    This study was purpose to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA-Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat.

  20. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  1. Hardware Segmentation on Digital Microscope Images for Acute Lymphoblastic Leukemia Diagnosis Using Xilinx System Generator

    Directory of Open Access Journals (Sweden)

    Prof. Kamal A. ElDahshan

    2014-09-01

    Full Text Available Image segmentation is considered the most critical step in image processing and helps to analyze, infer and make decisions especially in the medical field. Analyzing digital microscope images for earlier acute lymphoblastic leukemia diagnosis and treatment require sophisticated software and hardware systems. These systems must provide both highly accurate and extremely fast processing of large amounts of image data. In this work, the hardware segmentation framework for Acute Lymphoblastic Leukemia (ALL images based color histogram of Hue channel of HSV color space is proposed to segment each leukemia image into blasts and background using Field Programmable Gate Array (FPGA. The main purpose of this work is to implement image segmentation framework in a FPGA with minimum hardware resources and low execution time to be suitable enough for medical applications. Hardware framework of segmentation is designed using Xilinx System Generator (XSG as DSP design tool that enables the use of Simulink models, implemented in VHDL and synthesized for Xilinx SPARTAN-3E Starter kit (XC3S500E-FG320 FPGA.

  2. 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.

    Science.gov (United States)

    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

  3. T cell lymphoblastic leukaemia/lymphoma associated with a microenvironment of thymic asteroid B cells in the bone marrow.

    Science.gov (United States)

    Naresh, Kikkeri N; May, Philippa C; Reid, Alistair G; Marks, Alexandra J; Macdonald, Donald; Kanfer, Ed

    2010-10-01

      Asteroid B cells are a component of normal thymus. It is currently unclear whether these cells are identifiable in T cell lymphoblastic leukaemia/lymphoma (T-ALL/LBL) of the thymus. The aim of this study was to identify asteroid B cells both in thymic and extrathymic tissue involved by T-ALL/LBL.   Thymic, lymph node (LN) and bone marrow trephine biopsy (BMTB) samples from eight patients with T-ALL/LBL were reviewed. All had been investigated by immunohistochemistry and one by fluorescent in situ hybridization (FISH). The BMTB samples of two of eight T-ALL/LBLs and LN sample in one of them showed the presence of asteroid-shaped B cells with dendritic cytoplasmic processes. These B cells also expressed CD23 and the features were akin to the unique thymic asteroid B cells. Both patients had aggressive/resistant disease. Cytogenetic analysis in one showed a complex translocation involving the T cell receptor beta (TCRB) gene at 7q35 and a distal region of 9q known to harbour the NOTCH1 gene.   This is the first report of T-ALL/LBL documenting the presence of an asteroid B cell-rich microenvironment at bone marrow and LN sites. In this small subset, T-ALL/LBL cells are possibly dependent upon asteroid B cells, and whether targeting of asteroid B cells with anti-CD20 monoclonal antibody in such cases will result in clinical benefit remains to be determined. © 2010 Blackwell Publishing Limited.

  4. Results of external quality control study in flow cytometric acute lymphoblastic leukemia diagnostics

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2016-01-01

    Full Text Available Comparison of interpretation of acute lymphoblastic leukemia (ALL flow cytometric diagnostics data was the aim of the study. Immunophenotyping data obtained from 10 patients with ALL were analysed separately in 26 laboratories from Russian Federation and Kazahstan. Results comparison showed four main type of discordance: B-lineage ALL diagnostics during heavy bone marrow regeneration, great variability of T-ALL interpretation, complexity of ambiguous lineage acute leukemia and, finally, very different report types, unique for each laboratory. All these problems are the serious obstacles for standardization of flow cytometric ALL diagnostics in multicenter setting. Continuation of similar QC rounds following by consecutive discussions with further development of consensus diagnostic algorithm could be the first step for standardization of ALL immunophenotyping in Russian Federation and CIS countries.

  5. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute...... that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells. Udgivelsesdato: 1983-Jan-1...

  6. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Wang; Jun-Lin Liao; Dong Zhang; Li Wen

    2015-01-01

    Background: Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Methods: Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Results: Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Conclusion: Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  7. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sabine Topka

    2015-06-01

    Full Text Available Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL, the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  8. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Science.gov (United States)

    Topka, Sabine; Vijai, Joseph; Walsh, Michael F; Jacobs, Lauren; Maria, Ann; Villano, Danylo; Gaddam, Pragna; Wu, Gang; McGee, Rose B; Quinn, Emily; Inaba, Hiroto; Hartford, Christine; Pui, Ching-Hon; Pappo, Alberto; Edmonson, Michael; Zhang, Michael Y; Stepensky, Polina; Steinherz, Peter; Schrader, Kasmintan; Lincoln, Anne; Bussel, James; Lipkin, Steve M; Goldgur, Yehuda; Harit, Mira; Stadler, Zsofia K; Mullighan, Charles; Weintraub, Michael; Shimamura, Akiko; Zhang, Jinghui; Downing, James R; Nichols, Kim E; Offit, Kenneth

    2015-06-01

    Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  9. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Van Vlierberghe, Pieter; Pieters, Rob; Beverloo, H Berna; Meijerink, Jules P P

    2008-10-01

    Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

  10. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Mei, Lin; Ontiveros, Evelena P.; Griffiths, Elizabeth A.; Thompson, James E.; Wang, Eunice S.; Wetzler, Meir

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30 years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20–40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including L-asparaginase, glucocorticoids, 6-mercaptopruine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapy. PMID:25614322

  11. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant.

    Science.gov (United States)

    Wang, Guang-Xian; Liao, Jun-Lin; Zhang, Dong; Wen, Li

    2015-11-01

    Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  12. Cure rates of childhood acute lymphoblastic leukemia in Lithuania and the benefit of joining international treatment protocol

    DEFF Research Database (Denmark)

    Vaitkevičienė, Goda; Matuzevičienė, Rėda; Stoškus, Mindaugas

    2014-01-01

    BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest group of pediatric malignancies with long-term survival rates of more than 80% achieved in developed countries. Epidemiological data and survival rates of childhood ALL in Lithuania were lacking. Therefore, the aim of...

  13. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

    NARCIS (Netherlands)

    Marshall, G. M.; Dalla Pozza, L.; Sutton, R.; Ng, A.; de Groot-Kruseman, Ha; van der Velden, V. H.; Venn, N. C.; van den Berg, H.; de Bont, E. S. J. M.; Egeler, R. Maarten; Hoogerbrugge, P. M.; Kaspers, G. J. L.; Bierings, M. B.; van der Schoot, E.; van Dongen, J.; Law, T.; Cross, S.; Mueller, H.; de Haas, V.; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M. D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9; 22)-negative ALL, were

  14. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    NARCIS (Netherlands)

    Marshall, G.M.; Pozza, L. Dalla; Sutton, R.; Ng, A.; Groot-Kruseman, H.A. de; Velden, V.H. van der; Venn, N.C.; Berg, H. van den; Bont, E.S. de; rten Egeler, R. Maa; Hoogerbrugge, P.M.; Kaspers, G.J.L.; Bierings, M.B.; Schoot, E. van der; Dongen, J. Van; Law, T.; Cross, S.; Mueller, H.; Haas, V. de; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M.D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  15. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Gregers, J; Gréen, H; Christensen, I J

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...

  16. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

    NARCIS (Netherlands)

    Marshall, G. M.; Dalla Pozza, L.; Sutton, R.; Ng, A.; de Groot-Kruseman, Ha; van der Velden, V. H.; Venn, N. C.; van den Berg, H.; de Bont, E. S. J. M.; Egeler, R. Maarten; Hoogerbrugge, P. M.; Kaspers, G. J. L.; Bierings, M. B.; van der Schoot, E.; van Dongen, J.; Law, T.; Cross, S.; Mueller, H.; de Haas, V.; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M. D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9; 22)-negative ALL, were

  17. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    NARCIS (Netherlands)

    Marshall, G.M.; Pozza, L. Dalla; Sutton, R.; Ng, A.; Groot-Kruseman, H.A. de; Velden, V.H. van der; Venn, N.C.; Berg, H. van den; Bont, E.S. de; rten Egeler, R. Maa; Hoogerbrugge, P.M.; Kaspers, G.J.L.; Bierings, M.B.; Schoot, E. van der; Dongen, J. Van; Law, T.; Cross, S.; Mueller, H.; Haas, V. de; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M.D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  18. Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group

    NARCIS (Netherlands)

    T.D. Buitenkamp (Trudy); S. Izraeli (Shai); M. Zimmermann (Martin); E. Forestier (Erik); N.A. Heerema (Nyla); M.M. van den Heuvel-Eibrink (Marry); R. Pieters (Rob); C.M. Korbijn (Carin); L.B. Silverman (Lewis); K. Schmiegelow (Kjeld); D.-C. Liang (Der-Cheng); K. Horibe (Keizo); M. Aricò (Maurizio); A. Biondi (Andrea); G. Basso (Giuseppe); K.R. Rabin (Karin); M. Schrappe (Martin); G. Cario (Gunnar); G. Mann (Georg); M. Morak (Maria); R. Panzer-Grümayer (Renate); V. Mondelaers (Veerle); T. Lammens (Tim); H. Cavé (Hèléne); B. Stark (Batia); I. Ganmore (Ithamar); A.V. Moorman (Anthony); A. Vora (Ajay); S.P. Hunger (Stephen); C.H. Pui (Ching-Hon); C.G. Mullighan (Charles); A. Manabe (Atsushi); G. Escherich (Gabriele); J.R. Kowalczyk (Jerzy R.); J.A. Whitlock (James); C.M. Zwaan (Michel)

    2014-01-01

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

  19. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polym

  20. Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

    NARCIS (Netherlands)

    Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

    2001-01-01

    The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

  1. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    Directory of Open Access Journals (Sweden)

    Rana Baraz

    Full Text Available Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

  2. Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Plasschaert, S.L.A.; Groninger, E.; Boezen, M.; Kema, I.P.; Vries, E.G.F. de; Uges, D.R.A.; Veerman, A.J.P.; Kamps, W.A.; Vellenga, E.; Graaf, S.S.N. de; Bont, E.S. de

    2004-01-01

    OBJECTIVE: Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P-glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia. METHODS: From 52 of 70 children who participated in a previous study on vincris

  3. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim

    2011-01-01

    Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and toxic...

  4. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Sanjuan-Pla (Alejandra); C. Bueno (C.); C. Prieto (Cristina); P. Acha (Pamela); R.W. Stam (Ronald); R. Marschalek (Rolf); P. Menéndez (Pablo)

    2015-01-01

    textabstractInfant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinicalmanagement and survival (∼85-90%) of childhood B-ALL,

  5. Assessment of Mercaptopurine (6MP) Metabolites and 6MP Metabolic Key-Enzymes in Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Wojtuszkiewicz, A.; Barcelos, A.; Dubbelman, B.; Abreu, R.A. de; Brouwer, C.; Bökkerink, J.P.M.; Haas, V. de; Groot-Kruseman, H. de; Jansen, Gert; Kaspers, G.L.; Cloos, J.; Peters, G.J.

    2014-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this path

  6. 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...

  7. The association between glucocorticoid therapy and BMI z-score changes in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Arpe, Marie-Louise Hyre; Rørvig, Sascha; Kok, Karin

    2015-01-01

    PURPOSE: Few studies have addressed the common issue of weight gain in children with acute lymphoblastic leukemia (ALL) during early phases of treatment, and even fewer have used the appropriate measure for weight fluctuation in children, BMI-for-age z-scores (BAZs). The purpose of this study...

  8. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim Peder

    2011-01-01

    Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites...

  9. CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase.

    Science.gov (United States)

    Mehde, Atheer Awad; Yusof, Faridah; Adel Mehdi, Wesen; Zainulabdeen, Jwan Abdulmohsin

    2015-01-01

    ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

  10. The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6-7 May 2009

    DEFF Research Database (Denmark)

    Biondi, A; Baruchel, A; Hunger, S

    2009-01-01

    An international childhood acute lymphoblastic leukemia (ALL)working group was formed during the 27th annual meeting of the International Society of Pediatric Oncology in 1995. Since then, 10 workshops have been held to address many issues that help advance treatment outcome of childhood ALL...

  11. Hormone and thalidomide may be effective in the treatment of adult mediastinal T-cell lymphoblastic lymphoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hongyang Wu

    2013-06-01

    Full Text Available A case of a 53-year-old man with adult T-lymphoblastic lymphoma (T-LBL in mediastinum who survived more than 33 months in our hospital was reported. LBL was more common in schoolage and teenage boys than adults. The reported patient manifested progressive dyspnea. Chest CT scanning showed a huge irregular soft tissue shadow in anterior mediastinum which extended into posterior mediastinum and left chest wall. The tumor was 20 cm×15 cm×15 cm in size in left upper mediastinum and its boundaries with pericardium and left lower lung were unclear. The diagnosis of T-lymphoblastic lymphoma was confirmed by immunohistochemical staining. After surgery, he received five chemotherapy courses including Gem, CTX and VCR and biological therapies with IL-2 and IFN-α2b. About 16 months later, he complained of diplopia in the left eye without any evidence of recurrence. Blood examination which showed leukemoid reaction twice returned to normal after dehydration, hormone and thalidomide treatments. Finally, his condition became worse and died of pulmonary infection 33 months after first medical service. In summary, T-LBL is a rare disease which may result in poor prognosis even if the patient has received immediate chemotherapy. Hormone and thalidomide can be applied to treat adult T-LBL.

  12. Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Koramit Suppipat

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common hematological cancer in children. Although risk-adaptive therapy, CNS-directed chemotherapy, and supportive care have improved the survival of ALL patients, disease relapse is still the leading cause of cancer-related death in children. Therefore, new drugs are needed as frontline treatments in high-risk disease and as salvage agents in relapsed ALL. In this study, we report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of ALL cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. The treatment of ALL leukemic cells with sulforaphane resulted in dose-dependent apoptosis and G2/M cell cycle arrest, which was associated with the activation of caspases (3, 8, and 9, inactivation of PARP, p53-independent upregulation of p21(CIP1/WAF1, and inhibition of the Cdc2/Cyclin B1 complex. Interestingly, sulforaphane also inhibited the AKT and mTOR survival pathways in most of the tested cell lines by lowering the levels of both total and phosphorylated proteins. Finally, the administration of sulforaphane to the ALL xenograft models resulted in a reduction of tumor burden, particularly following oral administration, suggesting a potential role as an adjunctive agent to improve the therapeutic response in high-risk ALL patients with activated AKT signaling.

  13. Acute lymphoblastic leukemia presenting as a breast lump: A report of two cases

    Directory of Open Access Journals (Sweden)

    Syed Besina

    2013-01-01

    Full Text Available Extra-medullary leukemic infiltration of the breast by acute lymphoblastic leukemia (ALL is very rare. We report two cases of ALL presenting as breast masses and diagnosed on fine-needle aspiration (FNA. Our first patient, a post-partum 30-year-old female, developed bilateral breast lumps in her last trimester of pregnancy and complained of easy fatigability. Our second patient, a 14-year-old girl, presented with a right-breast lump of 1-week duration. She had received treatment for ALL 1 year back and had been in complete remission for the last 1 year. FNA of the breast nodules done in both the cases revealed diffuse infiltration by lymphoblasts. Subsequent hematological investigations confirmed bone marrow involvement by ALL in the first case and extra-medullary relapse in the second case. Fine-needle aspiration cytology (FNAC is an easy and cost effective method for the early diagnosis of metastatic leukemic infiltration, avoiding unnecessary excisional biopsies in such cases.

  14. Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation

    Directory of Open Access Journals (Sweden)

    Yadvinder Singh

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30-40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation. A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation.

  15. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    DEFF Research Database (Denmark)

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W

    2012-01-01

    with historical controls, we performed a retrospective national population-based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15-91 years......Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared......). The 5-year projected event-free survival (pEFS(5y) ) and overall survival (pOS(5y) ) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4-33·6] and 34·1% (95% CI 28·7-40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively...

  16. Acute T-cell lymphoblastic leukaemia presenting with cutaneous involvement in a child: a rare case report

    Directory of Open Access Journals (Sweden)

    Lohit Kumar Kalita

    2015-05-01

    Full Text Available Primary cutaneous involvement in T-cell lymphoblastic leukemia is rare in childhood. We present a case of 6-year-old girl admitted to our hospital because of multiple skin lesions. She was looked pale and weak. Generalized lymphadenopathy was present. Complete blood count revealed 216,000/mm3 white blood cell count. Peripheral blood smear showed 80% lymphoblasts. Bone marrow aspiration revealed 96% blastic cells with immunophenotype and morphological characteristics of acute lymphoblastic leukemia (T-ALL which was confirmed by flowcytometry. ALL BFM -95 remission induction treatment protocol was started. Skin lesion remained same after two month of the cytotoxic therapy. The symptoms became more aggressive and she died after 4 months of treatment. [Int J Res Med Sci 2015; 3(5.000: 1285-1287

  17. Malignant lymphoma of spleen presenting as acute pancreatitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Chao-Ming Wu; Lung-Chih Cheng; Gin-Ho Lo; Kwok-Hung Lai; Chia-Ling Cheng; Wen-Cheng Pan

    2007-01-01

    This is a case report of a patient who presented with acute pancreatitis without the common causes. A pancreatic biopsy revealed large B cell lymphoma. Spleen lymphoma with pancreatic involvement inducing acute pancreatitis, which is a rare disorder, was diagnosed.Here we also review the few similar cases reported in the literature.

  18. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

    Directory of Open Access Journals (Sweden)

    te Kronnie Geertruy

    2009-06-01

    Full Text Available Abstract Background The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL and myeloblastic leukemia (AML, with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes. Methods Using Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set + 78 (test set ALL and AML patients with (24+13 and without (116+65 MLL rearrangements have been investigated performing class comparison (SAM and class prediction (PAM analyses. Results We identified a MLL translocation-specific (379 probes signature and a phenotype-specific (622 probes signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements. Conclusion Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.

  19. Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse.

    Science.gov (United States)

    Sun, Congcong; Chang, Lixian; Zhu, Xiaofan

    2017-05-23

    ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R-positive ALL. We review here the most recent insights into the pathogenic mechanisms underlying E/R-positive ALL, as well as the molecular abnormalities prevailing at relapse.

  20. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  1. Role of L-asparaginase in acute lymphoblastic leukemia: focus on adult patients

    Directory of Open Access Journals (Sweden)

    Rytting ME

    2012-06-01

    Full Text Available Michael E RyttingDepartment of Pediatrics and Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Asparaginase preparations deplete asparagine in acute lymphoblastic leukemia (ALL blasts. Asparaginase in its various forms is an important component of treatment regimens for pediatric ALL. Recently, interest and use of asparaginase in adult patients with ALL has increased, particularly in young adults. There is much less information on asparaginase use and toxicity in adult compared with pediatric populations. This review surveys prior published studies of the three most commonly used asparagine preparations as used in adult patients, and discusses important toxicities encountered in adult patients who receive asparaginase preparations.Keywords: asparaginase, leukemia, adults, children

  2. Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia

    Science.gov (United States)

    Tosello, Valeria; Herranz, Daniel; Ambesi-Impiombato, Alberto; Da Silva, Ana Carolina; Sanchez-Martin, Marta; Perez-Garcia, Arianne; Rigo, Isaura; Castillo, Mireia; Indraccolo, Stefano; Cross, Justin R; de Stanchina, Elisa; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Basso, Giuseppe; Meijerink, Jules P; Cordon-Cardo, Carlos; Califano, Andrea; Ferrando, Adolfo A.

    2013-01-01

    SUMMARY Glucocorticoid resistance is a major driver of therapeutic failure in T-cell acute lymphoblastic leukemia (T-ALL). Here we identify the AKT1 kinase as a major negative regulator of the NR3C1 glucocorticoid receptor protein activity driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 impairs glucocorticoid-induced gene expression by direct phosphorylation of NR3C1 at position S134 and blocking glucocorticoid-induced NR3C1 translocation to the nucleus. Moreover, we demonstrate that loss of PTEN and consequent AKT1 activation can effectively block glucocorticoid induced apoptosis and induce resistance to glucocorticoid therapy. Conversely, pharmacologic inhibition of AKT with MK2206 effectively restores glucocorticoid-induced NR3C1 translocation to the nucleus, increases the response of T-ALL cells to glucocorticoid therapy and effectively reverses glucocorticoid resistance in vitro and in vivo. PMID:24291004

  3. Genetic loss of SH2B3 in acute lymphoblastic leukemia

    Science.gov (United States)

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A.; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K.

    2013-01-01

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis. PMID:23908464

  4. Hospitalisation for infection prior to diagnosis of acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Rostgaard, Klaus; Grau, Katrine

    2013-01-01

    . PROCEDURE: A nation-wide cohort encompassing all Danish children aged 0-14 years and born between 1977 and 2008 (N = 1,778,129) was established and followed for hospitalisations for infectious diseases and risk of childhood ALL. The exposure was lagged 1 year to limit reverse causality. In the statistical......BACKGROUND: It has been proposed that infections in infancy and early childhood are associated with a reduced risk of childhood acute lymphoblastic leukaemia (ALL). We tested this hypothesis in a register-based study of hospitalisations for infectious diseases prior to diagnosis of childhood ALL...... analyses exposure was defined as (time dependent) number of early or late (before 2 or at/after 2 years of age) hospitalisations to further explore possible age-dependent associations. RESULTS: A total of 815 children were diagnosed with ALL during follow-up. Risk of ALL was associated neither...

  5. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

  6. High Risk Pediatric Acute Lymphoblastic Leukemia: To Transplant or Not to Transplant?

    Science.gov (United States)

    Pulsipher, Michael A.; Peters, Christina; Pui, Ching-Hon

    2010-01-01

    Because survival with both chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) approaches to high risk pediatric acute lymphoblastic leukemia (ALL) generally improves through the years, regular comparisons of outcomes with either approach for a given indication are needed to decide when HSCT is indicated. Improvements in risk classification are allowing clinicians to identify patients at high risk for relapse early in their course of therapy. Whether patients defined as high risk by new methods will benefit from HSCT requires careful testing. Standardization and improvement of transplant approaches has led to equivalent survival outcomes with matched sibling and well-matched unrelated donors, however, survival using mismatched and haploidentical donors is generally worse. Trials comparing chemotherapy and HSCT must obtain sufficient data about therapy and stratify the analysis to assess the outcomes of best-chemotherapy with best-HSCT approaches. PMID:21195303

  7. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  8. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Minran; Fu, Yue; Sun, Ting; Chen, Jin; Qin, Xuemei; Yu, Yuan; Jia, Jihui; Chen, Chunyan

    2016-01-01

    Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID:27008505

  9. X-linked agammaglobulinemia associated with B-precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Hoshino, Akihiro; Okuno, Yusuke; Migita, Masahiro; Ban, Hideki; Yang, Xi; Kiyokawa, Nobutaka; Adachi, Yuichi; Kojima, Seiji; Ohara, Osamu; Kanegane, Hirokazu

    2015-02-01

    X-linked agammaglobulinemia (XLA) is clinically characterized by reduced number of peripheral B cells and diminished levels of serum immunoglobulins, and caused by a mutation in the Bruton's tyrosine kinase (BTK) gene, which play a pivotal role in signal transduction of pre-B-cell receptor (BCR) and BCR. B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children, and it may be associated with gene alterations that regulate B-cell development. Here we described a first case of XLA associated BCP-ALL. The whole-exome sequencing revealed a somatic mutation in MLL2 in the sample from the onset of BCP-ALL. This study suggests that the alterations of BTK and MLL2 synergistically function as leukemogenesis.

  10. 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

    ABSTRACT: Predicting the response to medical therapy and subsequently individualizing the treatment to increase efficacy or reduce toxicity has been a longstanding clinical goal. Not least within oncology, where many patients fail to be cured, and others are treated to or beyond the limit......, but also multiplied the complex interaction of genetic and other laboratory parameters that can be used for therapy adjustments. Thus, with the advances in the laboratory techniques, post laboratory issues have become major obstacles for treatment individualization. Many of these challenges have been...... 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...

  11. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.

    Science.gov (United States)

    Hogan, Laura E; Meyer, Julia A; Yang, Jun; Wang, Jinhua; Wong, Nicholas; Yang, Wenjian; Condos, Gregory; Hunger, Stephen P; Raetz, Elizabeth; Saffery, Richard; Relling, Mary V; Bhojwani, Deepa; Morrison, Debra J; Carroll, William L

    2011-11-10

    Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.

  12. Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

    Directory of Open Access Journals (Sweden)

    Marcela A. Chiabai

    2012-01-01

    Full Text Available This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL, and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

  13. Application of genomics for risk stratification of childhood acute lymphoblastic leukaemia: from bench to bedside?

    Science.gov (United States)

    Izraeli, Shai

    2010-10-01

    The remarkable progress in the treatment of childhood acute lymphoblastic leukaemia (ALL) has been based on the adjustment of therapy to subgroups of leukaemia stratified by their prognostic implications. Here, the contribution of the last decade of advanced genomic research on the clinical management of childhood ALL is examined. The application of genomics for routine diagnosis of ALL is feasible but depends on commercial development of appropriate certified platforms. The discovery of several novel high-risk markers, such as deletions in IKZF1 might be integrated into clinical protocols in the near future. Several novel targets for therapy have been identified and have led to phase I/II therapeutic trials. This and any future progress depends on the maintenance of high quality bio-banks including biological material and clinical data of each patient enrolled on a prospective clinical protocol. © 2010 Blackwell Publishing Ltd.

  14. Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Sallan, S E; Camitta, B M; Chan, D M; Traggis, D; Jaffe, N

    1977-01-01

    Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

  15. Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Whitehead, Todd P; Ward, Mary H; Colt, Joanne S; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B; Katharine Hammond, S; Rappaport, Stephen M; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.

  16. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism.

    Science.gov (United States)

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment.

  17. A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia.

    Science.gov (United States)

    Toya, Takashi; Shinohara, Akihito; Tatsuno, Keita; Seo, Sachiko; Nannya, Yasuhito; Ichikawa, Motoshi; Makimura, Koichi; Moriya, Kyoji; Kurokawa, Mineo

    2013-08-01

    Schizophyllum commune is a globally distributed basidiomycete fungus that is known as a rare cause of sinusitis, for which no prompt treatment has been established. We describe the first report of S. commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. Thirteen days after transplantation, a 23-year-old female developed maxillary and ethmoid sinusitis. The sinusitis was antimicrobial-resistant, and the sinus aspirate culture revealed white wooly mold, which was identified as S. commune by nucleotide sequencing. The patient was successfully treated with intravenous administration of liposomal amphotericin B for 2 months, followed by oral voriconazole. This report suggests the effectiveness of liposomal amphotericin B and voriconazole for S. commune infection in immunocompromised patients. Given the difficulty in distinguishing S. commune infection from aspergillosis by standard culture methods, the incidence of S. commune infection following allogeneic hematopoietic stem cell transplantation may be underestimated. Nucleotide sequencing may be useful in the diagnosis of S. commune infection.

  18. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  19. Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes

    DEFF Research Database (Denmark)

    Schmiegelow, K.

    2016-01-01

    Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all...... patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring...... cancer predisposing mutations can be challenging for both the physician and the patient due to their preexisting symptoms, their reduced tolerance to radio- and/or chemotherapy with enhanced risk of life-threatening organ toxicities, and the paucity of data from ALL patients with the same or similar...

  20. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  1. Executive function late effects in survivors of pediatric brain tumors and acute lymphoblastic leukemia.

    Science.gov (United States)

    Winter, Amanda L; Conklin, Heather M; Tyc, Vida L; Stancel, Heather; Hinds, Pamela S; Hudson, Melissa M; Kahalley, Lisa S

    2014-01-01

    Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function. Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group. Both BT and ALL demonstrated relative executive function weaknesses. As a group, BT survivors demonstrated weaker executive functioning than expected for age. Those BT survivors with deficits exhibited a profile suggestive of global executive dysfunction, while affected ALL survivors tended to demonstrate specific rapid naming deficits. Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans.

  2. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    Science.gov (United States)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  3. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Juan Pablo Castanedo-Cázares

    2015-01-01

    Full Text Available Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia.

  4. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  5. Hard palate perforation in acute lymphoblastic leukemia due to mucormycosis - a case report.

    Science.gov (United States)

    Samanta, Dipti R; Senapati, Surendra N; Sharma, Praveen K; Shruthi, B S; Paty, Prajna Bimoch; Sarangi, Gitanjali

    2009-03-01

    Palatal perforation can occur due to trauma, infection and malignancy. Mucormycosis is a rare opportunistic fungal infection caused by an organism of class zygomycetes. Rhinocerebral mucormycosis is the most common type of mucormycosis that typically starts in maxillary antrum in immunocompromised patients. Invasion of surrounding structures leads to necrotizing ulcer of the hard palate and ultimately leads to perforation. Here, we report a case of perforation of the hard palate due to mucormycosis in a eight years child having acute lymphoblastic leukemia (ALL), who was on prolonged chemotherapy and corticosteroid therapy. This case is being reported for its rarity. The aim of presenting this case report is to emphasize that the infection due to mucomycosis should be included in the differential diagnosis of hard palate perforation in ALL patients who are immunocompromised.

  6. Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Churchman, Michelle L; Low, Jonathan; Qu, Chunxu; Paietta, Elisabeth M; Kasper, Lawryn H; Chang, Yunchao; Payne-Turner, Debbie; Althoff, Mark J; Song, Guangchun; Chen, Shann-Ching; Ma, Jing; Rusch, Michael; McGoldrick, Dan; Edmonson, Michael; Gupta, Pankaj; Wang, Yong-Dong; Caufield, William; Freeman, Burgess; Li, Lie; Panetta, John C; Baker, Sharyn; Yang, Yung-Li; Roberts, Kathryn G; McCastlain, Kelly; Iacobucci, Ilaria; Peters, Jennifer L; Centonze, Victoria E; Notta, Faiyaz; Dobson, Stephanie M; Zandi, Sasan; Dick, John E; Janke, Laura; Peng, Junmin; Kodali, Kiran; Pagala, Vishwajeeth; Min, Jaeki; Mayasundari, Anand; Williams, Richard T; Willman, Cheryl L; Rowe, Jacob; Luger, Selina; Dickins, Ross A; Guy, R Kiplin; Chen, Taosheng; Mullighan, Charles G

    2015-09-14

    Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

  7. 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...

  8. Fatal Bacillus cereus endocarditis masquerading as an anthrax-like infection in a patient with acute lymphoblastic leukemia: case report.

    Science.gov (United States)

    Cone, Lawrence A; Dreisbach, Luke; Potts, Barbara E; Comess, Barbara E; Burleigh, William A

    2005-01-01

    A 38-year-old male farm worker with relapsing acute lymphoblastic leukemia spontaneously developed an ulcerating ulcer on his anterior thigh which was surrounded by a non-tender area of erythema. Bacillus cereus was isolated from the ulcer and blood, and the patient received intravenous penicillin and vancomycin for one week. When sensitivity studies were returned he was treated with gatifloxacin orally. After two weeks of combined antimicrobial therapy and negative blood cultures, the patient received combination chemotherapy with vincristine, prednisone, doxorubicin and cyclophosphamide. He was hospitalized a day after completing chemotherapy with neutropenic sepsis due to B. cereus. He received similar antimicrobial therapy as previously, but died three days later. At autopsy, the patient was found to have acute mitral valve endocarditis and bilateral brain abscesses. This was the first case of B. cereus endocarditis reported in a patient with acute lymphoblastic leukemia.

  9. EFFECTS OF A COMBINED AEROBIC AND STRENGTH TRAINING PROGRAM IN YOUTH PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Perondi

    2012-09-01

    Full Text Available Cure rates of youth with Acute Lymphoblastic Leukemia (ALL have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum, quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%, lat pull down (50%, leg press (73% and leg extension (64% as a result of the training (p < 0.01. The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life

  10. Role of the Erythropoietin Receptor in ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Inthal, Andrea; Krapf, Gerd; Beck, Dominik; Joas, Ruth; Kauer, Max O.; Orel, Lukas; Fuka, Gerhard; Mann, Georg; Panzer-Grümayer, E. Renate

    2014-01-01

    Purpose We explored the mechanisms leading to the distinct overexpression of EPOR as well as the effects of EPO signaling on ETV6/RUNX1-positive acute lymphoblastic leukemias. Experimental Design ETV6/RUNX1-expressing model cell lines and leukemic cells were used for real-time PCR of EPOR expression. Proliferation, viability, and apoptosis were analyzed on cells exposed to EPO, prednisone, or inhibitors of EPOR pathways by [3H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Annexin V/propidium iodide staining. Western blot analysis was done to detect activation of signaling proteins. Serum EPO levels and sequences of the EPOR (n = 53) as well as hemoglobin levels were taken from children with acute lymphoblastic leukemia enrolled in Austrian protocols. Results We show here that ectopic expression of ETV6/RUNX1 induced EPOR up-regulation. Anemia, however, did not appear to influence EPOR expression on leukemic cells, although children with ETV6/RUNX1-positive leukemias had a lower median hemoglobin than controls. Exposure to EPO increased proliferation and survival of ETV6/RUNX1-positive leukemias in vitro, whereas blocking its binding site did not alter cell survival. The latter was not caused by activating mutations in the EPOR but might be triggered by constitutive activation of phosphatidylinositol 3-kinase/Akt, the major signaling pathway of EPOR in these cells. Moreover, prednisone-induced apoptosis was attenuated in the presence of EPO in this genetic subgroup. Conclusions Our data suggest that ETV6/RUNX1 leads to EPOR up-regulation and that activation by EPO might be of relevance to the biology of this leukemia subtype. Further studies are, however, needed to assess the clinical implications of its apoptosis-modulating properties. PMID:19010836

  11. Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Perondi, Maria Beatriz; Gualano, Bruno; Artioli, Guilherme Gianini; de Salles Painelli, Vítor; Filho, Vicente Odone; Netto, Gabrieli; Muratt, Mavi; Roschel, Hamilton; de Sá Pinto, Ana Lúcia

    2012-01-01

    Cure rates of youth with Acute Lymphoblastic Leukemia (ALL) have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age) underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum), quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%), lat pull down (50%), leg press (73%) and leg extension (64%) as a result of the training (p children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life. Key pointsPatients with ALL present low muscle strength and poor quality of life.High-intensity resistance exercises combined with moderate-intensity aerobic exercise improved muscle strength and quality of life during the maintenance phase of ALL treatment.The exercise training program seemed to be tolerable and safe in ALL

  12. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Directory of Open Access Journals (Sweden)

    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  13. Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience

    Science.gov (United States)

    Özdemir, Nihal; Tüysüz, Gülen; Çelik, Nigar; Yantri, Leman; Erginöz, Ethem; Apak, Hilmi; Özkan, Alp; Yıldız, İnci; Celkan, Tiraje

    2016-01-01

    Aim: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. Material and Methods: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients’ files. Results: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. Conclusions: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving

  14. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

    2012-01-01

    Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors. PMID:22491738

  15. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Holleman, Amy; den Boer, Monique L; Kazemier, Karin M; Beverloo, H Berna; von Bergh, Anne R M; Janka-Schaub, Gritta E; Pieters, Rob

    2005-09-01

    Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia.

  16. Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia

    Science.gov (United States)

    Burmeister, Thomas; Gökbuget, Nicola; Schwartz, Stefan; Fischer, Lars; Hubert, Daniela; Sindram, Annette; Hoelzer, Dieter; Thiel, Eckhard

    2010-01-01

    Background The t(9;22) and t(4;11) chromosomal translocations, which generate the BCR-ABL and MLL-AF4 fusion genes, define high-risk subtypes of acute lymphoblastic leukemia in adults. However, the prognostic impact of other rarer fusion genes is less well established in adult acute lymphoblastic leukemia than in the childhood form. Design and Methods In the context of the German Multicenter Therapy Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) we used reverse transcriptase polymerase chain reaction to investigate 441 cases of BCR-ABL- and MLL-AF4-negative B-precursor acute lymphoblastic leukemia for the TCF3-PBX1 (E2A-PBX1) and ETV6-RUNX1 (TEL-AML1) fusion transcripts generated by the t(1;19)(q23;p13.3) and t(12;21)(p13;q22) translocations. Both are well-known molecular alterations in pediatric acute lymphoblastic leukemia in which they have favorable prognostic implications. Results We identified 23 adult patients with TCF3-PBX1 and ten with ETV6-RUNX1. In contrast to previous reports we found no significant difference in overall survival between TCF3-PBX1-positive and -negative patients. At 2 years after diagnosis all the ETV6-RUNX1-positive patients were alive and in continuous complete remission, but their long-term outcome was negatively affected by late relapses. TCF3-PBX1-positive patients exhibited a characteristic CD34−/CD33− and mostly cyIg+ immunophenotype. ETV6-RUNX1 only occurred in patients under 35 years old and was associated with a significantly lower white blood count. Conclusions In contrast to previous suggestions, adult patients with TCF3-PBX1-positive acute lymphoblastic leukemia do not appear to have a worse outcome than their negative counterparts. ETV6-RUNX1-positive patients had a very favorable performance status during the first few years but their long-term survival was negatively affected by late relapses. Both groups of patients are characterized by distinct clinicobiological features which facilitate their

  17. Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia.

    Science.gov (United States)

    Grönroos, Toni; Teppo, Susanna; Mehtonen, Juha; Laukkanen, Saara; Liuksiala, Thomas; Nykter, Matti; Heinäniemi, Merja; Lohi, Olli

    2017-03-01

    Cell signalling, which is often derailed in cancer, is a network of multiple interconnected pathways with numerous feedback mechanisms. Dynamics of cell signalling is intimately regulated by addition and removal of phosphate groups by kinases and phosphatases. We examined expression of members of the PTP4A family of phosphatases across acute leukemias. While expression of PTP4A1 and PTP4A2 remained relatively unchanged across diseases, PTP4A3 showed marked overexpression in ETV6-RUNX1 and BCR-ABL1 subtypes of precursor B cell acute lymphoblastic leukemia. We show that PTP4A3 is regulated by the ETV6-RUNX1 fusion, but noticed no marked impact on cell viability either after PTP4A3 silencing or treatment with a PTP4A3 inhibitor. Regulation of PTP4A3 expression is altered in specific subgroups of acute leukemias and this is likely brought about by expression of the aberrant fusion genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Current status of growth factors in the treatment of acute myeloid and lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, Oliver G; Bug, Gesine; Krauter, Jürgen

    2007-07-01

    The safety of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute leukemia has been well established in numerous clinical trials. The primary aim of these studies was to determine whether CSFs, when used as adjuncts to intensive chemotherapy, reduced the duration of neutropenia, prevented febrile neutropenia, infections, and hospitalization rates, and improved response and overall outcome in patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Despite considerable efforts in divers clinical settings, the potential advantages of hematopoietic growth factors in the management of these leukemias remain inconclusive. In general, individual published trials have shown declines in the incidence and/or duration of neutropenia but have not consistently demonstrated a reduction in the overall frequency of infectious complications or the duration of hospitalization. Most protocols also have failed to show a benefit in terms of disease-free or overall survival. Nevertheless, improvements in "soft" clinical end points, such as incidence of severe infections, may be clinically important and contribute, even if only incrementally, to the patient's quality of life. Selection of those patients likely to benefit from growth factors in a specific clinical setting is a worthwhile endeavour.

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

    Science.gov (United States)

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

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID:26137238

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

    Science.gov (United States)

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; Dabaghi, Mohammad; Nadimi, Motahareh

    2015-05-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia.

    Science.gov (United States)

    Weisberg, Stuart P; Smith-Raska, Matthew R; Esquilin, Jose M; Zhang, Ji; Arenzana, Teresita L; Lau, Colleen M; Churchill, Michael; Pan, Haiyan; Klinakis, Apostolos; Dixon, Jack E; Mirny, Leonid A; Mukherjee, Siddhartha; Reizis, Boris

    2014-02-13

    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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Bacillus cereus bacteremia and multiple brain abscesses during acute lymphoblastic leukemia induction therapy.

    Science.gov (United States)

    Hansford, Jordan R; Phillips, Marianne; Cole, Catherine; Francis, Joshua; Blyth, Christopher C; Gottardo, Nicholas G

    2014-04-01

    Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis, and rarely cerebral abscess. Here we report an 8-year-old boy undergoing induction therapy for acute lymphoblastic leukemia who developed multifocal B. cereus cerebral abscesses, highlighting the propensity for B. cereus to develop cerebral abscesses. A review of the literature over the past 25 years identified another 11 cases (3 children and 8 adults) of B. cereus cerebral abscess in patients undergoing cancer therapy. B. cereus cerebral abscesses were associated with a high mortality rate (42%) and significant morbidity. Notably, B. cereus bacteremia with concomitant cerebral abscess was associated with induction chemotherapy for acute leukemia in both children and adults (10 of 12 case reports). Our case report and review of the literature highlights the propensity for B. cereus to develop cerebral abscess(es). Therefore, early consideration for neuroimaging should be given for any neutropenic cancer patient identified with B. cereus bacteremia, in particular those with acute leukemia during induction therapy.

  4. Primary multifocal osseous lymphoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takashi S.P. [University of Iowa, Carver College of Medicine, Iowa City, IA (United States); Ferguson, Polly J. [University of Iowa, Department of Pediatrics, Iowa City, IA (United States); Khanna, Geetika [Washington University, Mallinckrodt Institute of Radiology, St Louis, MO (United States)

    2008-12-15

    We report a case of primary multifocal osseous lymphoma in a 6-year-old girl presenting with multifocal osteolytic lesions without systemic symptoms or identifiable non-osseous primary tumor. The differential diagnoses for such a presentation include histiocytosis X, chronic recurrent multifocal osteomyelitis, acute lymphoblastic leukemia, metastatic disease, and primary bone lymphoma. Although non-Hodgkin lymphoma is common in the pediatric population, its presentation as a primary bone tumor, especially with multifocal disease, is extremely rare and is frequently misdiagnosed. We hope that awareness of this entity will help radiologists achieve timely diagnosis and intervention. (orig.)

  5. An unusual cause of acute renal failure: renal lymphoma.

    Science.gov (United States)

    Ozaltin, Fatih; Yalçin, Bilgehan; Orhan, Diclehan; Sari, Neriman; Caglar, Melda; Besbas, Nesrin; Bakkaloglu, Aysin

    2004-08-01

    Renal involvement is a common finding in non-Hodgkin's lymphoma (NHL). Acute renal failure at initial presentation due to lymphomatous infiltration of the kidneys has been described infrequently. We report a 17-year-old male who presented with acute renal failure due to massive lymphomatous infiltration of the kidneys, which necessitated hemodialysis. The diagnosis of B-cell NHL was established by tru-cut biopsy of the kidneys and the patient had an excellent response to high-dose chemotherapy with no major complication. The presence of extrarenal involvement in the testes and the retroperitoneal lymph nodes made the diagnosis of primary renal lymphoma debatable. However, considering the delay in diagnosis and the high proliferative rate of B-cell NHL, we might postulate that the disease had originated primarily in the kidneys. We recommend that in NHL cases with severe renal involvement, full-dose chemotherapy should be instituted with meticulous clinical and laboratory follow-up in order to improve clinical and renal failure status rapidly and to avoid further dissemination of NHL.

  6. Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study.

    Science.gov (United States)

    Yeoh, Allen Eng Juh; Ariffin, Hany; Chai, Elaine Li Leng; Kwok, Cecilia Sze Nga; Chan, Yiong Huak; Ponnudurai, Kuperan; Campana, Dario; Tan, Poh Lin; Chan, Mei Yoke; Kham, Shirley Kow Yin; Chong, Lee Ai; Tan, Ah Moy; Lin, Hai Peng; Quah, Thuan Chong

    2012-07-01

    To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement. Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients. Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%). Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

  7. SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells.

    Science.gov (United States)

    Sprangers, M; Feldhahn, N; Liedtke, S; Jumaa, H; Siebert, R; Müschen, M

    2006-08-24

    Perpetual V(D)J recombinase activity involving multiple DNA double-strand break events in B-cell lineage leukemia and lymphoma cells may introduce secondary genetic aberrations leading towards malignant progression. Here, we investigated defective negative feedback signaling through the (pre-) B-cell receptor as a possible reason for deregulated V(D)J recombinase activity in B-cell malignancy. On studying 28 cases of pre-B-lymphoblastic leukemia and 27 B-cell lymphomas, expression of the (pre-) B-cell receptor-related linker molecule SLP65 (SH2 domain-containing lymphocyte protein of 65 kDa) was found to be defective in seven and five cases, respectively. SLP65 deficiency correlates with RAG1/2 expression and unremitting V(H) gene rearrangement activity. Reconstitution of SLP65 expression in SLP65-deficient leukemia and lymphoma cells results in downregulation of RAG1/2 expression and prevents both de novo V(H)-DJ(H) rearrangements and secondary V(H) replacement. We conclude that iterative V(H) gene rearrangement represents a frequent feature in B-lymphoid malignancy, which can be attributed to SLP65 deficiency in many cases.

  8. Meeting Report: Institute for Social Security and Services for State Workers (ISSSTE on Acute Lymphoblastic Leukaemia, Mexico City, Mexico, 3rd to 4th October 2016

    Directory of Open Access Journals (Sweden)

    Alvarado Ibarra Martha

    2017-06-01

    Full Text Available From October 3 to 4, 2016, the fourth meeting of haematologists who belonged to the institute for social security and services for state workers (ISSSTE was held, the meeting was held in Mexico City, Mexico. Attending this working meeting, medical fellows of the specialty of Haematology and Paediatric Haematology, as well as attached doctors of both specialties that work in different hospitals in Mexico City and the rest of the country, the purpose of the attendees to this consensus was discuss, update, and homogenize the protocols of diagnostic and therapeutic approach in patients with acute lymphoblastic leukaemia of all ages. All participants appreciated the opportunity to participate in one of the most important cooperation projects of the ISSSTE and to be able to offer updated treatment protocols to this population or, failing that, to send them a Medical Center that can provide hospital care as soon as possible. Physicians took advantage of this meeting for the scientific exchange, the discussion on projects in course and were planned the development of other consensuses being the closest the one of lymphomas. As in the previous consensuses that were published in a National magazine. The coordinator of this project raised to the attendees the possibility of a publication in magazines of greater prestige international since in countries like Mexico the cooperative work is not frequent and the group of haematologists belonging to ISSSTE are working towards this goal. This consensus was considered as a very well-organized platform to support the research of young fellows in the specialty to stimulate the team work in protocols of the different haematological pathologies and to inform the world the results achieved in a population of patients attended by the ISSSTE. In agreement with the main objective of this consensus on acute lymphoblastic leukaemia once finished and discussed throughout the haematological group, the coordinator for the

  9. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald;

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours a...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

  10. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    OpenAIRE

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting fr...

  11. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

    OpenAIRE

    Yotnda, P.; Garcia,F.; Peuchmaur, M.; Grandchamp, B.; Duval, M.; Lemonnier, F; Vilmer, E; Langlade-Demoyen, P

    1998-01-01

    Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > ...

  12. Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?

    OpenAIRE

    Belmonte, M; Hoofd, C.; Weng, A. P.; V. Giambra

    2016-01-01

    T-Cell acute lymphoblastic leukemia (t-all) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagatio...

  13. Cranial Radiation for Pediatric T-Lineage Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis

    OpenAIRE

    Kelly, Michael J.; Thomas A. Trikalinos; Dahabreh, Issa J.; Gianferante, Matthew; Parsons, Susan K.

    2014-01-01

    There are heterogeneous approaches to cranial irradiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n=5844). The average event-free survival (EFS) was higher by 6% per 5 years (p

  14. A soluble form of CTLA-4 is present in serum of pediatric patients with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    R. Simone

    2011-01-01

    Full Text Available CTLA-4 can regulate and maintain self-telerance, providing a negative signal limiting immunoresponses. Acute lymphoblastic leukemia is a clonal disorder of lymphoid progenitors representing the most frequent malignancy of childhood. Here, we show the presence of significantly elevated levels of a soluble form of CTLA-4 in 70% of B-ALL patients. A possible role of this soluble molecule in the pathogenesis of this neoplastic disease can be envisaged.

  15. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  16. MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

    Science.gov (United States)

    Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

    2016-11-01

    The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

  17. The prognosis of CALM-AF10-positive adult T-cell acute lymphoblastic leukemias depends on the stage of maturation arrest

    Science.gov (United States)

    Ben Abdelali, Raouf; Asnafi, Vahid; Petit, Arnaud; Micol, Jean-Baptiste; Callens, Céline; Villarese, Patrick; Delabesse, Eric; Reman, Oumedaly; Lepretre, Stephane; Cahn, Jean-Yves; Guillerm, Gaelle; Berthon, Céline; Gardin, Claude; Corront, Bernadette; Leguay, Thibaut; Béné, Marie-Christine; Ifrah, Norbert; Leverger, Guy; Dombret, Hervé; Macintyre, Elizabeth

    2013-01-01

    CALM-AF10 (also known as PICALM-MLLT10) is the commonest fusion protein in T-cell acute lymphoblastic leukemia, but its prognostic impact remains unclear. Molecular screening at diagnosis identified CALM-AF10 in 30/431 (7%) patients with T-cell acute lymphoblastic leukemia aged 16 years and over and in 15/234 (6%) of those aged up to 15 years. Adult CALM-AF10-positive patients were predominantly (72%) negative for surface (s)CD3/T-cell receptor, whereas children were predominantly (67%) positive for T-cell receptor. Among 22 adult CALM-AF10-positive patients treated according to the LALA94/GRAALL03-05 protocols, the poor prognosis for event-free survival (P=0.0017) and overall survival (P=0.0014) was restricted to the 15 T-cell receptor-negative cases. Among CALM-AF10-positive, T-cell receptor-negative patients, 82% had an early T-cell precursor phenotype, reported to be of poor prognosis in pediatric T-cell acute lymphoblastic leukemia. Early T-cell precursor acute lymphoblastic leukemia corresponded to 22% of adult LALA94/GRAALL03-05 T-cell acute lymphoblastic leukemias, but had no prognostic impact per se. CALM-AF10 fusion within early T-cell precursor acute lymphoblastic leukemia (21%) did, however, identify a group with a poor prognosis with regards to event-free survival (P=0.04). CALM-AF10 therefore identifies a poor prognostic group within sCD3/T-cell receptor negative adult T-cell acute lymphoblastic leukemias and is over-represented within early T-cell precursor acute lymphoblastic leukemias, in which it identifies patients in whom treatment is likely to fail. Its prognosis and overlap with early T-cell precursor acute lymphoblastic leukemia in pediatric T-cell acute lymphoblastic leukemia merits analysis. The clinical trial GRAALL was registered at Clinical Trials.gov number NCT00327678. PMID:23831922

  18. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

    Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  19. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Azevedo-Silva, F; Camargo, B de; Pombo-de-Oliveira, M S

    2010-03-01

    Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). The so-called 'adrenal hypothesis' emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  20. Secondary pure erythroid leukaemia in relapsed acute lymphoblastic leukaemia: lineage switch or chemotherapy effect?

    Science.gov (United States)

    Gupta, Sanjeev Kumar; Kumar, Rajive; Chharchhodawala, Taher; Kumar, Lalit

    2014-05-19

    Pure erythroid leukaemia is a rare subtype of acute myeloid leukaemia (AML) and its occurrence at acute lymphoblastic leukaemia (ALL) relapse has not been reported earlier. A 39-year-old man received chemotherapy for Philadelphia-negative B cell ALL. Subsequently, he developed pure erythroid leukaemia with >80% immature erythroid precursors in bone marrow showing block positivity on periodic acid-Schiff stain, expressing CD71, CD34 but lacking CD235a. The interval between exposure to multidrug chemotherapy including cyclophosphamide and AML diagnosis was 2 years and 9 months. No cytogenetic abnormality was detected at the time of relapse. The patient died 2 weeks after starting AML chemotherapy. The relatively narrow time interval (usually 5-10 years) between chemotherapy and AML development and normal karyotype at relapse raises a possibility of lineage switch besides therapy-related AML as the likely pathogenesis. Further exploration of such cases may unravel the pathways responsible for lineage assignment in pluripotent stem cells. 2014 BMJ Publishing Group Ltd.

  1. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

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    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

  2. Acute lymphoblastic leukemia subsequent to temozolomide use in a 26-year-old man: a case report

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    Shaikh Asim

    2010-08-01

    Full Text Available Abstract Introduction We report the development of acute lymphoblastic leukemia in a patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported. Case Presentation A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide. Conclusion Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, with an acceptable safety profile. Very few cases of myelodysplasia associated with temozolomide use have been reported. We report here the first case of acute lymphoblastic leukemia, which developed in a young man about one year after he finished taking temozolomide. This should provide further insight into a possible toxicity profile of this alkylating agent. This finding should be of interest to physicians in general and to medical oncologists in particular.

  3. Prognostic factors in children with acute lymphoblastic leukemia: a ten year study

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    Oloomi yazdi Z.

    2008-06-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common cancer in the pediatric population. With modern treatments, the chance of the complete recovery is nearly 100%. The most important prognostic factors are appropriate treatment protocol and determination of patient risk factors based on clinical, morphological, immunological and cytological characteristics. In this study we reviewed frequency of these factors, like as age, gender, the primary white blood cell number, sub- group on the base of FAB classification, immunophenotype and the clinical progress. Methods: In this retrospective study, we reviewed 877 pediatric patients with the diagnosis of ALL between the years of 1994 and 2004. In these patients the age, gender, primary WBC count, sub-group based on the FAB classification, immunophenotype and the clinical progress in 177 patient with acute lymphoblastic leukemia at Imam Khomeini Hospital between the years of 1994 to 2004 were determined. Results: Of these patients, 1.6% was younger than one year, 24.8% more than ten years old and 73.6% were between the ages of one and ten years; 63.8% were male. WBC counts were above 50,000/ul in 28.8% of the patients. FAB classifications included L1 in 80.2%, L2 in 17.5% and L3 in 2.3% of the patients. Immunophenotypes included pre-B cell in 63.8%, early pre-B cell in 23.1%, T cell in 12.3% and mature B cell in 0.8% of the patients. Marker CD10+ was detected in 88.1% of the B cell cases. In this study group, 74% of the patients recovered, 16.3% died and 16.5% relapsed.Conclusions: The prevalence of FAB-L1 and pre-B cell cases in this study is greater than a previous study, while the prevalence of FAB-L2 and early pre-B cell cases is less than that of the previous study.

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

    Science.gov (United States)

    2016-11-14

    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 Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  5. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: case report and literature review.

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    Zhang, Li-Dan; Li, Yan-Hong; Ke, Zhi-Yong; Huang, Li-Bin; Luo, Xue-Qun

    2012-01-01

    A 6-year-old boy with acute lymphoblastic leukemia in remission experienced hyperphagia, obesity, and emotional disorders. Cytomorphologic examination of cerebral spinal fluid (CSF) and cranial MRI did not help in differentiating between central nervous system leukemia (CNSL) and other CNS diseases including tuberculosis in this boy. Flow cytometric CSF analysis on repeated lumber puncture detected lymphoblasts, while microscopic CSF examination did not definitively show relapse disease. The diagnosis of CNSL was thus made and confirmed by the response to leukemia treatment. Obesity can be the first manifestation of CNSL and the diagnosis can be challenging. A combination of CSF cytomorphology, CSF flow cytometry, and cranial MRI can be useful in the diagnosis of the disease. Two mechanisms of CNSL-related obesity are discussed based on the literature review.

  6. Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia.

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    Kesler, Shelli R; Gugel, Meike; Huston-Warren, Emily; Watson, Christa

    2016-05-01

    Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness (p = 0.007) and network clustering coefficient (p = 0.019), as well as greater cognitive impairment (p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p regional connectivity.

  7. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies.

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    van Dongen, Jacques J M; van der Velden, Vincent H J; Brüggemann, Monika; Orfao, Alberto

    2015-06-25

    Monitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions. This is also why the efficacy of innovative drugs, such as antibodies and small molecules, are currently being evaluated with MRD diagnostics within clinical trials. In fact, MRD measurements might well be used as a surrogate end point, thereby significantly shortening the follow-up. The MRD techniques need to be sensitive (≤10(-4)), broadly applicable, accurate, reliable, fast, and affordable. Thus far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]-PCR) are claimed to meet these criteria, but classical flow cytometry does not reach a solid 10(-4), whereas classical ASO-PCR is time-consuming and labor intensive. Therefore, 2 high-throughput technologies are being explored, ie, high-throughput sequencing and next-generation (multidimensional) flow cytometry, both evaluating millions of sequences or cells, respectively. Each of them has specific advantages and disadvantages.

  8. Hypothalamus-pituitary-adrenal axis suppression following induction chemotherapy in children with acute lymphoblastic leukemia

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    Perdomo-Ramírez, Iván

    2016-01-01

    Full Text Available Background: Adrenal insufficiency has been reported in 46 % to 81.5 % of children receiving corticosteroids for acute lymphoblastic leukemia (ALL. Methodology: To assess the frequency of such insufficiency, 40 patients under 18 years (mean: 8.5 years with new diagnosis of ALL were studied. Base-line cortisol and adrenocorticotropin (ACTH levels were measured, and they received 5-week therapy with prednisolone. After 3 days off-steroid therapy, a stimulation test with ACTH 1 μg was done. In patients with abnormal cortisol (<18 μg/dL new ACTH tests were done and cortisol levels were determined at days 7, 14 and 30 until cortisol post-stimulation levels were normal. Results: Three days after the last steroid dose 29/40 (72.5 % had adrenal insufficiency after ACTH stimulus. At day 30 no one had abnormal cortisol levels after ACTH stimulus. All patients with adrenal suppression were over 5 years (HR 4.69; CI95 %: 1.44-15.32; p = 0.011. Conclusion: Steroids used during ALL treatment may cause adrenal insufficiency. Patients over 5 years are at high risk of developing adrenal suppression. We suggest to follow-up those patients with stress episodes after induction chemotherapy as steroid supplementation may be indicated.

  9. Effects of Malnutrition on Neutrophil/Mononuclear Cell Apoptotic Functions in Children with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Cakir, Fatma Betul; Berrak, Su Gülsün; Aydogan, Gonul; Tulunay, Aysin; Timur, Cetin; Canpolat, Cengiz; Eksioglu Demiralp, Emel

    2017-04-01

    Recent studies claim that apoptosis may explain immune dysfunction observed in malnutrition. The objective of this study was to determine the effect of malnutrition on apoptotic functions of phagocytic cells in acute lymphoblastic leukemia (ALL). Twenty-eight ALL patients (13 with malnutrition) and thirty controls were enrolled. Neutrophil and mononuclear cell apoptosis of ALL patients and the control group were studied on admission before chemotherapy and repeated at a minimum of three months after induction of chemotherapy or when the nutritional status of leukemic children improved. The apoptotic functions of both ALL groups on admission were significantly lower than those of the control group. The apoptotic functions were lower in ALL patients with malnutrition than those in ALL patients without malnutrition, but this was not statistically significant. The repeated apoptotic functions of both ALL groups were increased to similar values with the control group. This increase was found to be statistically significant. The apoptotic functions in ALL patients were not found to be affected by malnutrition. However, after dietary intervention, increased apoptotic functions in both ALL patient groups deserve mentioning. Dietary intervention should always be recommended as malnutrition or cachexia leads to multiple complications. Enhanced apoptosis might originate also from remission state of cancer.

  10. Lipoxygenase inhibitors protect acute lymphoblastic leukemia cells from ferroptotic cell death.

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    Probst, Lukas; Dächert, Jasmin; Schenk, Barbara; Fulda, Simone

    2017-09-15

    Ferroptosis has recently been identified as a mode of programmed cell death. However, little is yet known about the signaling mechanism. Here, we report that lipoxygenases (LOX) contribute to the regulation of RSL3-induced ferroptosis in acute lymphoblastic leukemia (ALL) cells. We show that the glutathione (GSH) peroxidase 4 (GPX4) inhibitor RSL3 triggers lipid peroxidation, production of reactive oxygen species (ROS) and cell death in ALL cells. All these events are impeded in the presence of Ferrostatin-1 (Fer-1), a small-molecule inhibitor of lipid peroxidation. Also, lipid peroxidation and ROS production precede the induction of cell death, underscoring their contribution to cell death upon exposure to RSL3. Importantly, LOX inhibitors, including the selective 12/15-LOX inhibitor Baicalein and the pan-LOX inhibitor nordihydroguaiaretic acid (NDGA), protect ALL cells from RSL3-stimulated lipid peroxidation, ROS generation and cell death, indicating that LOX contribute to ferroptosis. RSL3 triggers lipid peroxidation and cell death also in FAS-associated Death Domain (FADD)-deficient cells which are resistant to death receptor-induced apoptosis indicating that the induction of ferroptosis may bypass apoptosis resistance. By providing new insights into the molecular regulation of ferroptosis, our study contributes to the development of novel treatment strategies to reactivate programmed cell death in ALL. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.

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    Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka

    2013-01-01

    Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

  12. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

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    K P Kulkarni

    2010-01-01

    Full Text Available Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL. Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(es. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04. Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

  13. Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

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    Ruiling Liu

    2011-01-01

    Full Text Available Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL. Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI: 1.05–1.18, I2=18% during any time period, 1.25 (95% CI: 1.08–1.46, I2=53% preconception; 1.24 (95% CI: 1.07–1.43, I2=54% during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2=64% after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms.

  14. Bone Density in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL: A Literature Review

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    Ali Ghassemi

    2015-02-01

    Full Text Available Introduction:  Acute Lymphoblastic Leukemia (ALL is the most common malignancy in children and the main form of childhood leukemia (75%. ALL different treatment options have a great impact on children weight and appetite. The improving prognosis for children with cancer refocuses attention to long-term outcomes with an emphasis on quality of life. More survival rate allows researchers to evaluate long term complication of ALL and its different treatment options such as endocrine abnormalities for example decreased bone mineral density. METHODS:  a systematic web base search was conducted in MEDLINE up to December 2014. We included articles with available abstract in English language, and participants younger than 18 years. Manual searching was done within the reference list of articles.  Two reviewers independently reviewed and assessed eligibility criteria, assessed quality, and extracted data. RESULTS:  Trace elements concentration decline due to malabsorption or inadequate intake in children with ALL. Osteopenia occurs more frequent in younger children and those who treated with higher doses of corticosteroids. CONCLUSION:  The dietary history of ALL patients who are at more risk for fractures and osteopenia should be screened by paying more attention to calcium and vitamin D intake.

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

    Science.gov (United States)

    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.

  16. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

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    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  17. Redirecting T cells with Chimeric Antigen Receptor (CAR) for the treatment of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Biondi, Andrea; Magnani, Chiara F; Tettamanti, Sarah; Gaipa, Giuseppe; Biagi, Ettore

    2017-08-23

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Nowadays the survival rate is around 85%. Nevertheless, an urgent clinical need is still represented by primary refractory and relapsed patients who do not significantly benefit from standard approaches, including chemo-radiotherapy and hematopoietic stem cell transplantation (HSCT). For this reason, immunotherapy has so far represented a challenging novel treatment opportunity, including, as the most validated therapeutic options, cancer vaccines, donor-lymphocyte infusions and tumor-specific immune effector cells. More recently, unexpected positive clinical results in ALL have been achieved by application of gene-engineered chimeric antigen expressing (CAR) T cells. Several CAR designs across different trials have generated similar response rates, with Complete Response (CR) of 60-90% at 1 month and an Event-Free Survival (EFS) of 70% at 6 months. Relevant challenges anyway remain to be addressed, such as amelioration of technical, cost and feasibility aspects of cell and gene manipulation and the necessity to face the occurrence of relapse mechanisms. This review describes the state of the art of ALL immunotherapies, the novelties in terms of gene manipulation approaches and the problems emerged from early clinical studies. We describe and discuss the process of clinical translation, including the design of a cell manufacturing protocol, vector production and regulatory issues. Multiple antigen targeting and combination of CAR T cells with molecular targeted drugs have also been evaluated as latest strategies to prevail over immune-evasion. Copyright © 2017. Published by Elsevier Ltd.

  18. Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Esbenshade, Adam J; Friedman, Debra L; Smith, Webb A; Jeha, Sima; Pui, Ching-Hon; Robison, Leslie L; Ness, Kirsten K

    2014-01-01

    Children with acute lymphoblastic leukemia (ALL) are at increased risk of obesity and deconditioning from cancer therapy. This pilot study assessed feasibility/initial efficacy of an exercise intervention for patients with ALL undergoing maintenance therapy. Participants were aged 5 to 10 years, receiving maintenance therapy, in first remission. A 6-month home-based intervention, with written and video instruction, was supervised with weekly calls from an exercise coach. Pre- and poststudy testing addressed strength, flexibility, fitness, and motor function. Seventeen patients enrolled (participation 63%). Twelve (71%) finished the intervention, completing 81.7 ± 7.2% of prescribed sessions. Improvements of 5% or more occurred in 67% for knee and 75% for grip strength, 58% for hamstring/low-back and 83% for ankle flexibility, 75% for the 6-Minute Walk Test, and 33% for performance on the Bruininks-Oseretsky Test of Motor Proficiency Version 2. This pilot study demonstrated that exercise intervention during ALL therapy is feasible and has promise for efficacy.

  19. Dietary intake and childhood leukemia: The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) cohort study.

    Science.gov (United States)

    Ladas, Elena J; Orjuela, Manuela; Stevenson, Kristen; Cole, Peter D; Lin, Meiko; Athale, Uma H; Clavell, Luis A; Leclerc, Jean-Marie; Michon, Bruno; Schorin, Marshall A; Welch, Jennifer Greene; Asselin, Barbara L; Sallan, Stephen E; Silverman, Lewis B; Kelly, Kara M

    2016-10-01

    Children with acute lymphoblastic leukemia (ALL) are at elevated risk for nutrition-related morbidity both during and after therapy. We present the demographic characteristics and nutrient intake at study entry of a prospective cohort in which evaluating dietary intake in children diagnosed with ALL was investigated. Dietary intake data were collected for participants enrolled on the Dana-Farber Cancer Institute ALL Consortium Protocol. Dietary intake was assessed with a food frequency questionnaire and was compared with the dietary reference intake by ALL risk group (standard and high risk). Dietary intake data were collected from 81% of participants (n = 640). We found that 27% of participants were overweight/obese. Intake of total calories and other nutrients exceeded the dietary reference intake in up to 79% of children. This was evident in both risk groups and was pronounced among younger children. For micronutrients, dietary intake of calcium, vitamin D (females only), and zinc differed significantly between patients with standard-risk and those with high-risk ALL. This study was successful in collecting dietary intake data at the time of cancer diagnosis in a multicenter setting in a pediatric population at high-risk for nutrition-related morbidity. We identified "at-risk" dietary intakes, which vary by sex and ALL risk group; such patients may benefit from future dietary interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

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    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  1. Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia.

    Science.gov (United States)

    Gómez-Seguí, Inés; Cervera, Jose; Such, Esperanza; Martínez-Cuadrón, David; Luna, Irene; Ibáñez, Mariam; López-Pavía, María; Gascón, Adriana; Roig, Mónica; Martínez, Jesús; Sanz, Jaime; Montesinos, Pau; Martín-Aragonés, Guillermo; Lorenzo, Ignacio; Senent, Leonor; Barragán, Eva; Cordón, Lourdes; Sempere, Amparo; Sanz, Guillermo F; Sanz, Miguel Angel

    2012-01-01

    The prognostic value of cytogenetics in adult acute lymphoblastic leukemia (ALL) is not as established as in childhood ALL. We have analyzed the outcome and prognostic value of karyotype in 84 adults diagnosed with Philadelphia-negative ALL from a single institution that received induction chemotherapy and had successful karyotype performed. The most frequent finding was normal karyotype in 35 (42%) cases, followed by aneuploidies in 20 cases (24%) and t(4;11)(q21;q23)/MLL/AF4 in 5 (6%), and the remaining 24(27%) cases carried miscellaneous clonal abnormalities. The group of patients with t(4;11)(q21;q23)/MLL/AF4, hypodiploidy and low hyperdiploidy (less than 50 chromosomes) showed a worse outcome than those with normal karyotype and miscellaneous abnormalities in terms of overall survival (OS) (3 years OS; 47% vs. 13%, p = 0.014) and relapse-free survival (RFS) (3 years RFS; 44% vs. 27%, p = 0.005). Other cytogenetic prognostic classifications reported to date were tested in our series, but any was fully reproducible. In conclusion, karyotype is a useful tool for risk assessment in adult ALL. We have confirmed the bad prognosis of t(4;11)(q21;q23)/MLL/AF4 and hypodiploidy. Besides, low hyperdiploidy could also define a high-risk group of patients who might be candidates for more intensive treatment.

  2. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    Science.gov (United States)

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  3. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

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    Helen C. Atkinson

    2015-01-01

    Full Text Available Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL and treated with modern COG protocols (n=80 to determine longitudinal changes in body mass index (BMI and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5% were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004 for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7. Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005, disease risk (P<0.0001, age (P=0.0001, and BMI z-score (P<0.0001 at diagnosis and total dose of steroid during maintenance (P=0.01. Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  4. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

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    Idalia Garza-Veloz

    2015-01-01

    Full Text Available Background. Acute lymphoblastic leukemia type B (B-ALL is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05. There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27. The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05. Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

  5. First-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults.

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    Ottmann, Oliver G; Pfeifer, Heike

    2009-06-01

    The tyrosine kinase inhibitor (TKI) imatinib has become an integral part of front-line therapy for Philadelphia chromosome-positive acute lymphoblastic leukaemia, with remission rates exceeding 90% irrespective of whether imatinib is given alone or combined with chemotherapy. Treatment outcome with imatinib-based regimens has improved compared with historic controls, but most patients who do not undergo allogeneic stem cell transplantation (SCT) eventually relapse. Second-generation TKI, e.g. dasatinib and nilotinib, show activity against most of the bcr-abl tyrosine kinase domain mutations involved in acquired imatinib resistance, but clinical benefit is generally short lived. Accordingly, SCT in first complete response is considered to be the best curative option. Strategies to improve outcome in patients ineligible for transplantation as well as after SCT include front-line treatment with more effective TKI to increase molecular response rates. Following SCT, the pre-emptive use of imatinib appears to reduce the relapse rate. Novel immunotherapeutic interventions and combinations of TKI are also being explored.

  6. TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia

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    Chu, Ming; Yin, Kailin; Dong, Yujun; Wang, Pingzhang; Xue, Yun; Zhou, Peng; Wang, Yuqi; Wang, Yuedan

    2017-01-01

    Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR). During the 4-week VXLD treatment, the level of TFDP3 increased 4-fold. High expression of TFDP3 was identified in the re-emerging lines (Jurkat/MRD) with increased chemoresistance, which is correlated with partially promoter demethylation of TFDP3. Downregulation of TFDP3 by RNA interference reversed chemoresistance in Jurkat/MRD accompanied by reinstated E2F1 activity that coincided with increased levels of p53, p73, and associated proapoptotic target genes. Importantly, TFDP3 silencing in vivo induced apparent benefit to overcome chemoresistance in combination with VXLD treatment. Collectively, TFDP3 confers chemoresistance in MRD within childhood T-ALL, indicating that TFDP3 is a potential gene therapy target for residual cancer. PMID:27902457

  7. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase

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    Pieters, Rob; Hunger, Stephen P; Boos, Joachim; Rizzari, Carmelo; Silverman, Lewis; Baruchel, Andre; Goekbuget, Nicola; Schrappe, Martin; Pui, Ching-Hon

    2010-01-01

    Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available; the native asparaginase derived from Escherichia coli (E. coli-asparaginase), a pegylated form of this enzyme (PEG-asparaginase) and a product isolated from Erwinia chrysanthemi, i.e. Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E.coli-asparaginase, lead to inactivation of E-Coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli-asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another product to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, there is much debate regarding the optimal formulation and dosage of these agents. This manuscript provides an overview of available evidence to make recommendations for optimal use of Erwinia asparaginase in the treatment of ALL. PMID:20824725

  8. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

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    Yuan-Fang Liu

    2016-06-01

    Full Text Available Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

  9. Characterization of Pediatric Acute Lymphoblastic Leukemia Survival Patterns by Age at Diagnosis

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    Md Jobayer Hossain

    2014-01-01

    Full Text Available Age at diagnosis is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL survivorship. However, literature providing adequate assessment of the survival variability by age at diagnosis is scarce. The aim of this study is to assess the impact of this prognostic factor in pediatric ALL survival. We estimated incidence rate of mortality, 5-year survival rate, Kaplan-Meier survival function, and hazard ratio using the Surveillance Epidemiology and End Results (SEER data during 1973–2009. There was significant variability in pediatric ALL survival by age at diagnosis. Survival peaked among children diagnosed at 1–4 years and steadily declined among those diagnosed at older ages. Infants (<1 year had the lowest survivorship. In a multivariable Cox proportional hazard model stratified by year of diagnosis, those diagnosed in age groups 1–4, 5–9, 10–14, and 15–19 years were 82%, 75%, 57%, and 32% less likely to die compared to children diagnosed in infancy, respectively. Age at diagnosis remained to be a crucial determinant of the survival variability of pediatric ALL patients, after adjusting for sex, race, radiation therapy, primary tumor sites, immunophenotype, and year of diagnosis. Further research is warranted to disentangle the effects of age-dependent biological and environmental processes on this association.

  10. Isolated testicular relapse in acute lymphoblastic leukemia - Effective treatment with the modified CCG-112 protocol

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    Shama Goyal

    2005-01-01

    Full Text Available BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR. MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

  11. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

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    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  12. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia.

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    Robien, Kim; Ness, Kirsten K; Klesges, Lisa M; Baker, K Scott; Gurney, James G

    2008-11-01

    Recent studies indicate that survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention recommendations, the Dietary Approaches to Stop Hypertension (DASH) diet, and the 2005 United States Department of Agriculture (USDA) Food Guide. Mean daily energy intake was consistent with estimated requirements; however, mean body mass index was 27.1 kg/m2 (overweight). Dietary index scores averaged fewer than half the possible number of points on all 3 scales, indicating poor adherence to recommended guidelines. No study participant reported complete adherence to any set of guidelines. Although half the participants met minimal daily goals for 5 servings of fruits and vegetables (WCRF/AICR recommendations) and Food Guide), participants reported dietary sodium and added sugar intake considerably in excess of recommendations, and suboptimal consumption of whole grains. Guideline adherence was not associated with either body mass index or waist circumference, perhaps due to the low dietary index scores. These findings suggest that dietary intake for many adult survivors of childhood ALL is not concordant with dietary recommendations that may help reduce their risk of obesity, cardiovascular disease, or other treatment-related late effects.

  13. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study.

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    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y; Petridou, Eleni; Dockerty, John D; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G; Ashton, Lesley J; Dessypris, Nikolaos; Kang, Alice Y; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-04-15

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.

  14. Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.

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    Harrison, Christine J; Schwab, Claire

    2016-03-01

    In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer.

  15. Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia.

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    Januszkiewicz, D A; Nowak, J S

    1994-09-01

    DNA-based PCR with various sets of primers for TCR gamma/delta, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3, V delta 2 to D delta 2, or D delta 3 to D delta 2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of V gamma I group, the most frequent gene usage concerns regions V gamma 2, V gamma 4, and psi V gamma 7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.

  16. Anthropometry in Long-Term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence.

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    Collins, Laura; Beaumont, Lesley; Cranston, Amy; Savoie, Stefanie; Nayiager, Trishana; Barr, Ronald

    2017-06-01

    Body mass index (BMI) is an inadequate measure of nutritional status in children and adolescents with cancer as it does not distinguish muscle from adipose tissue. However, arm anthropometry offers simple assessments of fat mass and lean body mass; especially valuable in low- and middle-income countries where the great majority of young people with cancer live and access to sophisticated expensive measures of body composition is markedly limited. The nutritional status of 75 long-term survivors of acute lymphoblastic leukemia was assessed by arm anthropometry, in addition to BMI, in a cross-sectional cohort study. Normal ranges for triceps skin fold thickness (TSFT, a surrogate for fat mass) and mid-upper arm circumference (MUAC, a surrogate for lean body mass) were between the 15th and 85th percentiles for age and sex. Overweight/obesity was classified as a TSFT >85th percentile and sarcopenia as an MUAC 25 and by TSFT; and 20% of the subjects had a TSFT >95th percentile. Only two subjects were sarcopenic. None met the combined criteria for sarcopenic obesity. TSFT and MUAC/height indices did not add sensitivity to identification of sarcopenia or obesity. TSFT is a useful measure of overweight/obesity in this population, but MUAC does not identify a notable proportion with sarcopenia. Further resolution may be provided by more sophisticated measures of body composition.

  17. Biomarker identification and pathway analysis by serum metabolomics of childhood acute lymphoblastic leukemia.

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    Bai, Yunnuo; Zhang, Haitao; Sun, Xiaohan; Sun, Changhao; Ren, Lihong

    2014-09-25

    Acute lymphoblastic leukemia (ALL) is a common hematological malignant neoplasm that typically affects children. Although intense chemotherapeutic regimens have been useful to combat the disease, approximately 20% of patients will relapse despite treatment. Diagnosing ALL requires bone marrow puncture procedure, which many parents do not consent to for it is invasive. Additionally, metabolic alterations associated with the disease are unclear. Metabolic alterations associated with ALL were investigated by performing serum metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Ingenuity Pathways Analysis (IPA) was also performed. Thirty metabolites (17 detected in positive mode and 13 in negative mode) were differentially expressed between patients with ALL and control patients; these metabolites were selected as potential biomarkers. Based on IPA analysis, glycerophospholipid metabolism is deregulated in patients with ALL and may represent an underlying metabolic pathway associated with disease progression. Metabolomics can be used to analyze the metabolic activity of ALL patients compared to healthy controls. The data we provide here suggest that glycerophospholipid metabolism may be a key mechanism underlying disease progression and development. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

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    González, A; Cortina, L; González, P; González, C; García, T; de Svarch, E G

    2004-05-01

    Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

  19. Effect of Malnutrition at Diagnosis on Clinical Outcomes of Children With Acute Lymphoblastic Leukemia.

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    Yazbeck, Nadine; Samia, Loma; Saab, Raya; Abboud, Miguel R; Solh, Hassan; Muwakkit, Samar

    2016-03-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Although studies have shown that malnutrition can negatively affect treatment outcome, results are controversial. This retrospective study aims at determining the prevalence of malnutrition and its association with treatment outcome among children with ALL treated at the Children's Cancer Institute in Lebanon. A total of 103 patients diagnosed with ALL between April 2002 and May 2010 were enrolled. Anthropometric data were collected from medical records upon diagnosis, at 3 and 6 months, and at the end of treatment. Body mass index was calculated for children 2 years of age and older, whereas weight-for-height ratio was used for patients below 2 years. Patients were considered underweight, stunted, or wasted if their Z-scores were <-2 SD. The prevalence of malnourished children was 25.2% at diagnosis and remained almost the same at the end of treatment. The odds of having a poor outcome (death and relapse) was higher among malnourished children and more so among stunted children with an odds ratios=2.15; 95% confidence interval, 0.5-8.3 and odds ratio=2.63; 95% confidence interval, 0.6-11.5, respectively. Although there was a trend showing worse outcomes in malnourished children with ALL at diagnosis when compared with well-nourished children larger studies using additional tools like arm anthropometry need to be conducted to prove the association.

  20. Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

    Science.gov (United States)

    Spiers, A S; Roberts, P D; Marsh, G W; Parekh, S J; Franklin, A J; Galton, D A; Szur, Z L; Paul, E A; Husband, P; Wiltshaw, E

    1975-12-13

    Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

  1. UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia

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    Benyoucef, Aissa; Palii, Carmen G.; Wang, Chaochen; Porter, Christopher J.; Chu, Alphonse; Dai, Fengtao; Tremblay, Véronique; Rakopoulos, Patricia; Singh, Kulwant; Huang, Suming; Pflumio, Francoise; Hébert, Josée; Couture, Jean-Francois; Perkins, Theodore J.; Ge, Kai; Dilworth, F. Jeffrey; Brand, Marjorie

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients. PMID:26944678

  2. TET2 promoter DNA methylation and expression analysis in pediatric B-cell acute lymphoblastic leukemia

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    Ewa Musialik

    2014-03-01

    Full Text Available TET2 is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL. Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45 ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children’s normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.

  3. Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Tonorezos, Emily S; Snell, Peter G; Moskowitz, Chaya S; Eshelman-Kent, Debra A; Liu, Jennifer E; Chou, Joanne F; Smith, Stephanie M; Dunn, Andrea L; Church, Timothy S; Oeffinger, Kevin C

    2013-08-01

    Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited. To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest. Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ≥ 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54). Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population. Copyright © 2013 Wiley Periodicals, Inc.

  4. The risk factors for thrombosis in children with acute lymphoblastic leukemia.

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    Sivaslioglu, Selda; Gursel, Turkiz; Kocak, Ulker; Kaya, Zuhre

    2014-09-01

    We aimed to scrutinize the risk factors for thrombosis in children with acute lymphoblastic leukemia treated with the Berlin-Frankfurt-Münster 95 protocol. The study population was 82 children younger than 16 years of age. The children were followed up for 10 years until January 2007. Thrombosis occurred in 10 (12%) of 82 patients during the treatment course, mainly after the M protocol. The most common risk factor was factor V Leiden (FVL; 15.6%). This was followed by methyleneterahydrofolate reductase (MTHFR; 9.3%), elevated lipoprotein (1.5%), and prothrombin (PT) 20210A (1.5%) in descending order. The risk of thrombosis was found to be significantly high in patients with FVL mutation (odds ratio = 7.1, 95% confidence interval = 1.6-30.5). The risk of thrombosis was not significant in patients with MTHFR and PT20210A mutation (P = .2). Age, catheter usage, FVL mutation, and prednisolone treatment are significant risk factors for thromboemboli occurrence.

  5. Age and leukocyte count as prognostic factors on acute lymphoblastic leukemia: hgmlal07 cohort

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    Washington Ladines-Castro

    2016-07-01

    Full Text Available In order to establish the cutoff with prognostic implications for white blood cell count and age at diagnosis in adults with acute lymphoblastic leukemia (ALL, we conducted an observational, descriptive and analytical study nested in a retrospective cohort of patients with ALL treated by institutional protocol HGMLAL07 during 2007-2014. We study 255 patients, the 52.9% (n=135 were female and 47.1% (n=120 were male. The mean age was 31 (16-80 years-old. The disease-free survival (DFS decreases in both genders after 20 years-old (p = 0.001. Leukocyte count average was 56.1 x 109/L (0.1-850 x 109/L. DFS decreases significantly from an equal or greater leukocyte count of 20 x 109/L (p<0.05. With this results, we can conclude that use foreign cutoff for age and leukocyte count could determine a bad prognosis stratification and a consequent suboptimal treatment.

  6. Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

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    Muhterem Duyu

    2014-01-01

    Full Text Available Dysregulation of microRNA (miRNA expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.

  7. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  8. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  9. Acute lymphoblastic leukemia masquerading as juvenile rheumatoid arthritis: diagnostic pitfall and association with survival.

    Science.gov (United States)

    Marwaha, Ram Kumar; Kulkarni, Ketan Prasad; Bansal, Deepak; Trehan, Amita

    2010-03-01

    Acute lymphoblastic leukemia (ALL) often presents with osteoarthritic manifestations which may lead to misdiagnosis with juvenile rheumatoid arthritis (JRA). This study was designed to identify ALL patients with initial diagnosis of JRA, compare their clinicolaboratory characteristics and outcome with other ALL patients treated at our center. Case records of 762 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy and outcome were recorded. Of the children, 49 (6.4%) had initial presentation mimicking JRA. Asymmetric oligoarthritis was the most common pattern of joint involvement. Majority presented with fever, pallor, arthritis, night pain, and bone pain. None of the routine prognostic factors including age, gender, lymphadenopathy, hepatosplenomegaly, total leukocytes count (TLC), and platelet count were significantly associated with relapse/death. The mean symptom-presentation interval (SPI), hemoglobin was significantly higher whilst the TLC was significantly lower in these patients compared to other ALL patients. The 5 year overall-survival was better than other patients with ALL (p = 0.06, by logrank test). Significantly longer SPI in these patients underscores the need for prompt and early investigations to rule out ALL in patients of JRA with atypical features and pointers of ALL. Children with ALL-mimicking JRA may belong to a subgroup of ALL with a better prognosis.

  10. Challenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults

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    Levine SR

    2016-02-01

    Full Text Available Selena R Levine,1 Jennifer L McNeer,2 Michael S Isakoff1 1Center for Cancer and Blood Disorders, Connecticut Children’s Medical Center and University of Connecticut School of Medicine, Hartford, CT, 2Section of Pediatric Hematology/Oncology, University of Chicago Comer Children's Hospital, Chicago, IL, USA Abstract: The survival rate for children with acute lymphoblastic leukemia (ALL has dramatically improved over the last 50 years. However, for those in the adolescent and young adult (AYA age-group of 15–30 years with ALL, there has not been the same degree of improvement. Historically, pediatric and adult providers have utilized different treatment approaches based on clinical trials. However, studies that have compared the outcome of AYA patients with ALL treated on pediatric or adult clinical trials have generally shown substantially better outcomes for this patient population treated with the pediatric trials. Additionally, hematopoietic stem cell transplantation has been considered as part of intensified therapy for AYA patients with ALL. Herein, we review the outcomes with chemotherapy alone and with hematopoietic stem cell transplantation, and explore the challenges faced in determining the ideal therapy for the AYA population of patients. Keywords: adolescent young adult oncology, leukemia, hematopoietic stem cell transplantation

  11. CENTRAL NERVOUS SYSTEM INVOLVEMENT IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSTIC TOOLS, PROPHYLAXIS AND THERAPY

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    Maria Ilaria Del Principe

    2014-11-01

    Full Text Available In adult patients with acute lymphoblastic leukemia (ALL, Central Nervous System (CNS involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC and flow cytometry (FCM. Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. Actually, early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogenic hematopoietic stem cell transplantation might be considered. This review will discuss risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it.

  12. Early adolescent language development following intrathecal chemotherapy for acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lewis, Fiona M; Bohan, Jaycie K

    2017-04-10

    Central nervous system (CNS) prophylaxis in the treatment of childhood acute lymphoblastic leukaemia (ALL) is routinely achieved through intrathecal chemotherapy (ITC). The presence of high level language deficits in older children who received CNS-directed ITC for ALL in early childhood is yet to be elucidated, with previous research suggesting that high level language deficits may appear later in ALL survivors' development at an age when these skills typically emerge. A test battery covering foundational language skills and higher-order language skills was administered to five participants (aged 10-15 years) with a history of ITC for ALL. Conversion of each child's language performance scores to z scores allowed for clinical interpretation of data across the language areas tested. Foundational language skills were, in general, of no clinical concern. Three of the five children presented with clinically impaired language skills in areas including resolving ambiguity, making inferences and composing novel sentences. Performance variation between the participants and within the individual participants was noted. Given the importance of early adolescent language abilities to academic and social development in late primary and secondary schooling, these preliminary findings suggest further research into emerging adolescent language abilities following ITC for ALL is warranted.

  13. Psychological Impact of Chemotherapy for Childhood Acute Lymphoblastic Leukemia on Patients and Their Parents.

    Science.gov (United States)

    Sherief, Laila M; Kamal, Naglaa M; Abdalrahman, Hadel M; Youssef, Doaa M; Abd Alhady, Mohamed A; Ali, Adel S A; Abd Elbasset, Maha Aly; Hashim, Hiatham M

    2015-12-01

    To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents.The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients.The study revealed significant low level of self-esteem in 84.83% of patients. Their parents had significant psychological stress. PSI was significantly associated with parents' low sense of competence, negative attachment to their children, feeling of high restriction, high depression, poor relation to spouse, high social isolation variables of parent's domains. It was significantly associated with low distraction, negative parents' reinforcement, low acceptability, and high demanding variables of child's domains. Long duration of disease was the most detrimental factor among demographic data of the patients.Chemotherapy for ALL has a significant impact on the psychological status of both patients and their parents with high prevalence of low self-esteem in children and high degree of stress in their parents.

  14. Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

    Science.gov (United States)

    Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

    2013-06-01

    Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (pfebrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed.

  15. Educatin given to parents of children newly diagnosed with acute lymphoblastic leukemia: the parent's perspective.

    Science.gov (United States)

    Aburn, Gemma; Gott, Meryn

    2014-01-01

    Over the last 30 years, diagnosis and treatment of childhood cancers have improved significantly due to medical research and advancements in technology. Increasingly, parents are taking on the role of providing "nursing" care for their children, including managing emergency situations as well as everyday treatment needs. This study investigated the perceptions and experiences of parents caring for newly diagnosed children with acute lymphoblastic leukemia (ALL) in relation to education given prior to the first discharge from hospital. Using a grounded theory approach, 12 parents of children with ALL from a tertiary pediatric hematology and oncology setting in New Zealand were interviewed using a semi-structured interview technique. Key findings of relevance to clinical practice include the importance of recognizing the emotional strain parents experience following diagnosis and the resultant impact upon how education is understood. Findings may also be applicable to other complex child health areas where education is provided, both in a local and international context. Understanding the family perspective is crucial to enabling clinicians to provide appropriate and informative education to children with ALL and their families.

  16. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase.

    Science.gov (United States)

    Pieters, Rob; Hunger, Stephen P; Boos, Joachim; Rizzari, Carmelo; Silverman, Lewis; Baruchel, Andre; Goekbuget, Nicola; Schrappe, Martin; Pui, Ching-Hon

    2011-01-15

    Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.

  17. RALLE pilot: response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children.

    Science.gov (United States)

    Saarinen-Pihkala, Ulla M; Parto, Katriina; Riikonen, Pekka; Lähteenmäki, Päivi M; Békàssy, Albert N; Glomstein, Anders; Möttönen, Merja

    2012-05-01

    Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.

  18. Childhood T-cell acute lymphoblastic leukaemia expressing "Ia-like" antigen:" a case report.

    Science.gov (United States)

    Kupa, A; Beckman, I G; Bradley, J; Moore, H; Thomas, M; Zola, H; Cheney, K; Rice, M; Toogood, I

    1982-01-01

    A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.

  19. Approach to prediagnostic clinical semiology, noticed by mothers, of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Castro-Jiménez, Miguel Ángel; Rueda-Arenas, Ernesto; Cabrera-Rodríguez, Daladier

    2015-08-01

    Recognizing early symptoms of acute lymphoblastic leukemia (ALL) may help to make an early diagnosis. The objective of this study is to identify clinical manifestations preceding the diagnosis of childhood ALL from the maternal perspective and to establish the time elapsed from the first manifestation to the diagnosis. Six hospitals located in Bogotá and Bucaramanga (Colombia) participated. Cases consisted of children under 15 years old with incidental diagnosis of ALL between January 2000 and March 2005. Data on sociodemographic characteristics, pre diagnostic clinical manifestations, first symptom, and time to diagnosis were collected during interviews with mothers. Medians, ranges and proportions were estimated. P values below 0.05 were considered significant. One hundred and twenty-eight cases were analyzed. Pallor (83.6%), loss of appetite (72.6%), weight loss (62.5%), andbleeding into the skin (39.1%) were the most common symptoms preceding diagnosis. The delay between the occurrence of the first symptom and the diagnosis of ALL depends on what the first manifestation is, and it maybe shorter when there is evidence of hemorrhage (median= 14 days). The presence of palpable lymph nodes in the armpits was more significant in girls than in boys (p= 0.04). Childhood ALL symptomatology in the prediagnostic stage is not specific to this disease; however, the clinical sign and time since its occurrence may serve as a guide in the early stage of this disease.

  20. Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Wang, Jingting; Yao, Nengliang; Wang, Yuanyuan; Zhou, Fen; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-04-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies. © The Author(s) 2015.

  1. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.

    Science.gov (United States)

    von Bergh, Anne R M; Beverloo, H Berna; Rombout, Paul; van Wering, Elisabeth R; van Weel, Margreet H; Beverstock, Geoffrey C; Kluin, Philip M; Slater, Rosalyn M; Schuuring, Ed

    2002-09-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia.

  2. Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia

    Science.gov (United States)

    Ness, Kirsten K.; Kaste, Sue C.; Zhu, Liang; Pui, Ching-Hon; Jeha, Sima; Nathan, Paul C.; Inaba, Hiroto; Wasilewski-Masker, Karen; Shah, Durga; Wells, Robert J.; Karlage, Robyn E.; Robison, Leslie L.; Cox, Cheryl L.

    2014-01-01

    This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 (range 4–18) years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL), enrolled on a physical activity trial from 2009 to 2013. Outcomes were measured 7-10 days after diagnosis and compared to age- and sex-specific expected values. Associations between function and HRQL were evaluated with logistic regression. Children low values for BMD z-scores/height (mean±standard error: −0.53±0.16 vs. 0.00±0.14, p <0.01), body mass index percentile (57.6±3.15 vs. 50.0±3.27%, p=0.02), quadriceps strength (201.9±8.3 vs. 236.1±5.4 Newtons, p<0.01), six minute walk distance (385.0±13.1 vs. 628.2±7.1 meters, p < 0.001), and Bruininks-Oseretsky Test of Motor Proficiency (23±2.5 vs. 50±3.4%, p < 0.001). Quadriceps weakness was associated with a 20.9-fold (95% CI 2.5–173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning. PMID:25030039

  3. ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Abir Gmidène

    2009-01-01

    Full Text Available In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL, and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH for the t(12;21. This translocation leads ETV6-RUNX1 (previously TEL-AML1 fusion gene. 16 patients (28% had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12 identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21 among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

  4. Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Sutaryo

    2008-11-01

    Full Text Available Abstract Background Most studies on Health-related Quality of Life (HRQOL in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. Methods After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™ 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™ 3.0 Cancer Module. Results Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2–5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p Conclusion Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.

  5. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

    Science.gov (United States)

    Moorman, Anthony V.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

  6. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. VARIATIONS OF THE LEUKOCYTES AND LYMPHOCYTES IN THE CASE OF ACUTE LYMPHOBLASTIC LEUKEMIA

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    Mirela Cozma

    2005-01-01

    Full Text Available The purpose of this study is to approximate the surviving period in patients with acute lymphoblastic leukemia. For this study we took in to consideration 10 patients 0 to 20 years old, coming from rural or urban environments and their evolution has been studied for a period of 60 days from the primary presentation to the hospital. The diagnosis was made after a careful history and physical examination and was completed after a blood count insisting on the number of leukocytes and on the peripheral blood smear. The patients’ evolution was monitored through the hematological parameters of the peripheral blood smear and of the bone marrow. The main Para clinical investigations consisted in the white cells and lymphocytes count from the peripheral blood smear. We counted the absolute and relative number of lymphocytes from the peripheral blood smear of these patients and then we divided them into three groups by criteria of age. We took into consideration at every age group the causes of the primary presentation to the hospital.

  9. Development of resistance to dasatinib in Bcr/Abl-positive acute lymphoblastic leukemia

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    Fei, Fei; Stoddart, Sonia; Müschen, Markus; Kim, Yong-mi; Groffen, John; Heisterkamp, Nora

    2010-01-01

    Dasatinib is a potent dual Abl/Src inhibitor approved for treatment of Ph-positive leukemias. At a once-daily dose and a relatively short half-life of 3-5 hours, tyrosine kinase inhibition is not sustained. However, transient inhibition of K562 leukemia cells with a high-dose pulse of dasatinib or long-term treatment with a lower dose was reported to irreversibly induce apoptosis. Here, the effect of dasatinib on treatment of Bcr/Abl-positive acute lymphoblastic leukemia (ALL) cells was evaluated in the presence of stromal support. Dasatinib eradicated Bcr/Abl ALL cells, caused significant apoptosis and eliminated tyrosine phosphorylation on Bcr/Abl, Src, Crkl and Stat-5. However, treatment of mouse ALL cells with lower doses of dasatinib over an extended period of time allowed the emergence of viable drug-resistant cells. Interestingly, dasatinib treatment increased cell surface expression of CXCR4, which is important for survival of B-lineage cells, but this did not promote survival. Combined treatment of cells with dasatinib and a CXCR4 inhibitor resulted in enhanced cell death. These results do not support the concept that long-term treatment with low dose dasatinib monotherapy will be effective in causing irreversible apoptosis in Ph-positive ALL, but suggest that combined treatment with dasatinib and drugs such as AMD3100 may be effective. PMID:20111071

  10. Acute lymphoblastic leukemia in adolescents and young adults – from genomics to the clinics

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    Kenderian SS

    2013-04-01

    Full Text Available Saad Sirop Kenderian, Mark R Litzow Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Acute lymphoblastic leukemia (ALL in adolescents and young adults (AYA represents a unique and challenging disease entity. Despite the recent improvement of survival in this population over the last decade, it is still lagging behind the excellent cure rates obtained in pediatric ALL. This special population of AYA receives care from pediatric as well as adult hematologists and can be treated on pediatric or adult protocols. There is a substantial difference in disease biology, response to chemotherapy, and allogeneic stem cell transplantation between pediatric and AYA patients. This review discusses current controversies in the management of AYA, outcomes following treatment with pediatric and adult protocols, and the role of allogeneic stem cell transplantation. It focuses on the unique clinical, biological, and socioeconomic characteristics of this population that might partly explain the inferior outcomes. This review also explores recent advances in genomic profiling and emerging treatments in ALL. Keywords: novel agents, monoclonal antibodies, stem cell transplantation, bone marrow transplantation, Philadelphia positive ALL, genomic profile

  11. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

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    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  12. Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

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    Vesely, C; Frech, C; Eckert, C; Cario, G; Mecklenbräuker, A; zur Stadt, U; Nebral, K; Kraler, F; Fischer, S; Attarbaschi, A; Schuster, M; Bock, C; Cavé, H; von Stackelberg, A; Schrappe, M; Horstmann, M A; Mann, G; Haas, O A; Panzer-Grümayer, R

    2017-01-01

    Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1’s critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias. PMID:27899802

  13. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

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    Jaime-Perez, Jose Carlos; Carrillo-Sanchez, Karol; Ramos-Del Hoyo, Maria Guadalupe; Lugo-Trampe, Angel; Gutierrez-Aguirre, Cesar Homero; Gonzalez-Llano, Oscar; Salazar-Riojas, Rosario; Hidalgo-Miranda, Alfredo; Gomez-Almaguer, David

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. PMID:25802479

  14. Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia.

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    Simons, Annet; Stevens-Kroef, Marian; El Idrissi-Zaynoun, Najat; van Gessel, Sabine; Weghuis, Daniel Olde; van den Berg, Eva; Waanders, Esmé; Hoogerbrugge, Peter; Kuiper, Roland; van Kessel, Ad Geurts

    2011-12-01

    In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray-based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray-deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (< 5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray-based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray-based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting.

  15. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

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    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  16. Alteration in Bone Mineral Metabolism in Children with Acute Lymphoblastic Leukemia (ALL: A Review

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    Chowdhury Yakub Jamal

    2009-11-01

    Full Text Available In recent years there has been a significant increase in event free survival (EFS and overall survival in children with cancer. As survival rates for childhood cancer have radically improved, late effects associated with the successful but highly intensive chemotherapy and/or radiotherapy have dramatically increased. Many possible late effects of cancer treatment are recognized in pediatric cancer patients as infertility, endocrine deficiency, renal failure, pulmonary and cardiac toxicity, obesity and osteopenia/osteoporosis. Decreased bone mineral density (BMD and bone metabolism disturbances have been recognized and reported in literature. Osteopenia/osteoporosis skeletal abnormalities, osteonecrosis and pathological fractures are known to occur frequently in childhood acute lymphoblastic leukemia (ALL at diagnosis, during and after treatment with chemotherapy. Various studies have revealed different metabolic alterations related to ALL. Some suggestions have been made about their relationship with the disease process. Various metabolic abnormalities may be encountered in the newly diagnosed ALL patients. It includes decreased and increased serum levels of calcium and phosphate. Hypercalcemia may result from leukemic infiltrations of bone and release of parathormone like substance from lymphoblast. Elevated serum phosphate can occur as a result of leukemic cell lysis and may induce hypocalcemia. It has been postulated by other authors that leukemic cells may directly infiltrate bone and produce parathroid hormone related peptides, prostaglandin E and osteoblast inhibiting factors. Hypomagnesemia, hypocalcaemia and hypothyroidisum have been demonstrated in patients with ALL. Some patients may have poor nutrition and decreased physical activities during treatment. However postulations have also been made that chemotherapy may play a role in creating metabolic alterations in children with ALL. Corticosteroid, methotraxate and cranial irradiations

  17. Letter regarding Zhao et al. entitled " DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia".

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    Deenen, Maarten J; Henricks, Linda M; Sonke, Gabe S; Schellens, Jan Hm; Meulendijks, Didier

    2017-06-01

    Zhao et al. investigated the association between germline genetic polymorphisms in DPYD, the gene encoding dihydropyrimidine dehydrogenase, and (1) the risk of developing pediatric acute lymphoblastic leukemia and (2) outcome of acute lymphoblastic leukemia following the treatment with 5-fluorouracil plus oxaliplatin (FOLFOX). The authors found that the common DPYD variant c.85T>C (rs1801265, DPYD*9A) was significantly associated with (1) risk of developing pediatric acute lymphoblastic leukemia, (2) complete response rate, (3) event-free survival, and (4) treatment-related toxicity. The authors conclude that patients carrying the c.85T>C C allele have an increased risk of developing acute lymphoblastic leukemia and have inferior outcome, and that DPYD c.85T>C can be used as a guide for individualized treatment and the decision to utilize 5-fluorouracil in acute lymphoblastic leukemia patients. In our view, the published article gives rise to multiple critical issues regarding the study's rationale and the methodology used, which strongly question the validity of the authors' conclusions.

  18. Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Sabin, Noah D.; Pei, Deqing; Yang, Jun J.; Khan, Raja B.; Panetta, John C.; Krull, Kevin R.; Inaba, Hiroto; Rubnitz, Jeffrey E.; Metzger, Monika L.; Howard, Scott C.; Ribeiro, Raul C.; Cheng, Cheng; Reddick, Wilburn E.; Jeha, Sima; Sandlund, John T.; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

    2014-01-01

    Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. Conclusion MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity. PMID:24550419

  19. 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.

  20. Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and oral cancer

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    Jen-Yang Tang

    2012-03-01

    Full Text Available Isocitrate dehydrogenase (IDH encodes a nicotinamide adenine dinucleotide phosphate+-dependent enzyme for oxidative decarboxylation of isocitrate and has an essential role in the tricarboxylic acid cycle. Mutations of IDH1 and IDH2 have been identified in patients with glioma, leukemia, and other cancers. However, the incidence of IDH mutations in acute myeloid leukemia in Taiwan is much lower than that reported in Western countries. The reason for the difference is unknown and its clinical implications remain unclear. Acute lymphoblastic leukemia (ALL is a heterogenous hematopoietic malignancy. Oral squamous cell carcinoma (OSCC results from chronic carcinogen exposures and is highly prevalent in trucking workers, especially in southern Taiwan. Subtypes of both diseases require specific treatments, and molecular markers for developing tailored treatments are limited. High-resolution melting (HRM analysis is now a widely used methodology for rapid, accurate, and low-cost mutation scanning. In this study, 90 adults with OSC and 31 children with ALL were scanned by HRM analysis for IDH1 and IDH2 mutation hot spots. In ALL, the allele frequency was 3.23% in both IDH1 and IDH2. In OSCC, the allele frequency was 2.22% in IDH2. A synonymous mutation over pG313 (c.939A > G of IDH2 was found in both pediatric ALL and adult OSCC. Therefore, we concluded that mutations of IDH are uncommon in ALL and OSCC and are apparently not a major consideration when selecting treatment modalities.