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Sample records for childhood leukemia relapse

  1. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan;

    2016-01-01

    .001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless......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...... included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P

  2. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition

    NARCIS (Netherlands)

    Szczepanski, T.; Velden, V.H. van der; Waanders, E.; Kuiper, R.P.; Vlierberghe, P. Van; Gruhn, B.; Eckert, C.; Panzer-Grumayer, R.; Basso, G.; Cave, H.; Stadt, U.Z.; Campana, D.; Schrauder, A.; Sutton, R.; Wering, E. van; Meijerink, J.P.P.; Dongen, J.J. van

    2011-01-01

    PURPOSE: Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL mig

  3. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

    Directory of Open Access Journals (Sweden)

    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.

  4. Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Stefan Essig

    Full Text Available BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL. Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36, which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%. Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6 compared to those without (55.8;p=0.005, but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

  5. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs.

    Science.gov (United States)

    Gómez, Ana M; Martínez, Carolina; González, Miguel; Luque, Alfonso; Melen, Gustavo J; Martínez, Jesús; Hortelano, Sonsoles; Lassaletta, Álvaro; Madero, Luís; Ramírez, Manuel

    2015-10-01

    We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.

  6. 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

  7. Childhood Leukemia

    Science.gov (United States)

    ... fast growing type while chronic leukemia grows slowly. Children with leukemia usually have one of the acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes ...

  8. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner;

    2015-01-01

    associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...

  9. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

    Science.gov (United States)

    Riccheri, María C.; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-01

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths. PMID:27058755

  10. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

    NARCIS (Netherlands)

    Biondi, A; Valsecchi, MG; Seriu, T; D'Aniello, E; Willemse, MJ; Fasching, K; Pannunzio, A; Gadner, H; Schrappe, M; Kamps, WA; Bartram, CR; van Dongen, JJM; Panzer-Grumayer, ER

    2000-01-01

    The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case

  11. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

    Science.gov (United States)

    Uderzo, C; Grazia Zurlo, M; Adamoli, L; Zanesco, L; Aricò, M; Calculli, G; Comelli, A; Cordero di Montezemolo, L; Di Tullio, M T; Guazzelli, C

    1990-04-01

    Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

  12. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was re...

  13. Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: failure of subsequent treatment with cyclophosphamide, cytosine arabinoside, vincristine and prednisone (COAP).

    Science.gov (United States)

    Sallan, S E; Hitchcock-Bryan, S

    1981-01-01

    Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 2 1/2-5 years of continuous disease-free remission, 20-25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequate for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.

  14. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner;

    2015-01-01

    defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates...

  15. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Childhood AML Treatment Research Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute ... Myelogenous Leukemia Treatment Hairy Cell Leukemia Treatment Past treatment for cancer and certain genetic conditions affect the ...

  16. 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

  17. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-26

    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 Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  18. 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

  19. Childhood Leukemia and Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Alpaslan Türkkan

    2009-12-01

    Full Text Available In this review, the relationship between very low frequency electromagnetic fields, originating from high voltage powerlines, and childhood leukemia was evaluated. Electromagnetic fields have biological effects. Whole populations are effected by different levels of electromagnetic fields but children are more sensible. In urban areas high voltage powerlines are the main sources of electromagnetic fields. The relation of electromagnetic fields due to high voltage powerlines and leukemia with consideration of dose-response and distance is investigated in several studies. There are different opinions on the effects of electromagnetic fields on general health. The relation between electromagnetic fields and childhood leukemia must be considered separately. Although there is no limit value, it is generally accepted that exposure to 0.4 µT and over doubles the risk of leukemia in children 15 years and younger. (Journal of Current Pediatrics 2009; 7: 137-41

  20. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

  1. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2016-08-03

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  2. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  3. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

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

  4. 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

  5. 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.

  6. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    Science.gov (United States)

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  7. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood 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; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  8. Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

    Science.gov (United States)

    Messina, C; Valsecchi, M G; Aricò, M; Locatelli, F; Rossetti, F; Rondelli, R; Cesaro, S; Uderzo, C; Conter, V; Pession, A; Sotti, G; Loiacono, G; Santoro, N; Miniero, R; Dini, G; Favre, C; Meloni, G; Testi, A M; Werner, B; Silvestri, D; Arrighini, A; Varotto, S; Pillon, M; Basso, G; Zanesco, L

    1998-01-01

    The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

  9. Relapsed/Refractory acute myeloid leukemia patients | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available Treatment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...tment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...on(s) being investigated Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia... language Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia acuta mieloide re...arbazina nei pazienti affetti da leucemia acuta mieloide recidivata/refrattaria i cui blasti esprimono bassi

  10. Infection and childhood leukemia: review of evidence

    Directory of Open Access Journals (Sweden)

    Raquel da Rocha Paiva Maia

    2013-12-01

    Full Text Available OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection, and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

  11. Definition of Cure in Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Inaba, Hiroto; Leung, Wing; Pounds, Stanley; Cao, Xueyuan; Campana, Dario; Ribeiro, Raul C.; Pui, Ching-Hon

    2014-01-01

    Background A better understanding of when cure can be declared in childhood acute myeloid leukemia (AML) would reduce anxiety and improve quality of life of AML survivors. We determined the likelihood of patients with AML to maintain long-term remission after completion of therapy. Patients and Methods The cumulative risk of relapse, time to relapse, event-free survival and overall survival were analyzed for 604 patients with AML enrolled in seven successive clinical trials, divided into 3 treatment eras (1976–1991, 1991–1997, 2002–2008). Results The median time to relapse did not change over time (0.93 years vs. 0.76 vs. 0.8 years for each consecutive era, P = .22) but the risk of relapse decreased significantly (5-year cumulative incidence of relapse 52.6% ± 3.1% vs. 31.5% ± 3.9% vs. 22.0% ± 3.0%, P < .001). Among patients who were in remission 4 years from diagnosis, the probabilities of relapse were 1.7%, 2.9%, and 0.9%, respectively. In the most recent era, all 44 relapses except one occurred within four years of diagnosis. Conclusion Children with AML who are treated with contemporary therapy and remain in remission four years from diagnosis are likely cured. Although late relapses and late deaths from other causes are rare, long-term follow up of survivors is necessary for timely management of late adverse effects. PMID:24798038

  12. Global characteristics of childhood acute promyelocytic leukemia.

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Sequential Administration of Methotrexate and Asparaginase in Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Buaboonnam, Jassada; Cao, Xueyuan; Pauley, Jennifer L.; Pui, Ching-Hon; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Inaba, Hiroto

    2014-01-01

    Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was 3 (range, 1-4). Six patients responded to treatment (3 had morphologic complete remission with incomplete blood count recovery, 2 had partial remission, and 1 had stable disease for 16 months), and 4 are still alive. Three of 6 responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (9 patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (2 patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. PMID:23335430

  18. How Is Childhood Leukemia Classified?

    Science.gov (United States)

    ... tissues and organs beyond the bone marrow. These children often have fever, poor appetite, and weight loss. At this point the CML acts much like an aggressive acute leukemia (AML or, less often, ALL). Not ... questions about what phase your child’s CML is in, be sure to have the ...

  19. How Is Childhood Leukemia Diagnosed?

    Science.gov (United States)

    ... the organs. The echoes are converted by a computer into an image on a computer screen. This is a fairly easy test to ... material. For reprint requests, please see our Content Usage Policy . Early Detection, Diagnosis, and Types Can Childhood ...

  20. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Pounds, Stanley; Cao, Xueyuan; Jenkins, Laura; Dahl, Gary; Bowman, W. Paul; Taub, Jeffrey W; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Inaba, Hiroto

    2013-01-01

    Background Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). The impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. Methods Clinical outcome and causes of treatment failure of 351 patients enrolled on three consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. Results The more recent protocol (AML02) produced improved outcomes for 10- to 21-year-old patients compared to 2 earlier studies (AML91 and 97), with 3-year rates of event-free survival (EFS), overall survival (OS) and cumulative incidence of refractory leukemia or relapse (CIR) for this group similar to those of 0- to 9-year old patients: EFS, 58.3% ± 5.4% vs. 66.6% ± 4.9%, P=.20; OS, 68.9% ± 5.1% vs. 75.1% ± 4.5%, P=.36; cumulative incidence of refractory leukemia or relapse, 21.9% ± 4.4%; vs. 25.3% ± 4.1%, P=.59. EFS and OS estimates for 10–15-year-old patients overlapped those for 16–21-year-old patients. However, the cumulative incidence of toxic death was significantly higher for 10- to 21-year-old patients compared to younger patients (13.2% ± 3.6 vs. 4.5% ± 2.0%, P=.028). Conclusion The survival rate for older children with AML has improved on our recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID:22674050

  1. Surviving childhood leukemia: career, family, and future expectations.

    Science.gov (United States)

    Brown, Chris; Pikler, Vanessa I; Lavish, Lea A; Keune, Kristen M; Hutto, C J

    2008-01-01

    The authors examine the impact of childhood leukemia on the career development of 11 young adult survivors, using consensual qualitative research. They discuss the results and implications of childhood leukemia on the survivor's career, family, and future expectations, and provide recommendations for addressing the critical coping and management challenges encountered by survivors, their families, and the helping professionals who treat them.

  2. 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

  3. Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.

    Science.gov (United States)

    Bailey, Helen D; Infante-Rivard, Claire; Metayer, Catherine; Clavel, Jacqueline; Lightfoot, Tracy; Kaatsch, Peter; Roman, Eve; Magnani, Corrado; Spector, Logan G; Th Petridou, Eleni; Milne, Elizabeth; Dockerty, John D; Miligi, Lucia; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Simpson, Jill; Zhang, Luoping; Rondelli, Roberto; Baka, Margarita; Orsi, Laurent; Moschovi, Maria; Kang, Alice Y; Schüz, Joachim

    2015-12-01

    Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.

  4. 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.

  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. 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

  7. Extramedullary Relapse of Acute Myeloid and Lymphoid Leukemia in Children: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Jee Young Kim

    2016-05-01

    Full Text Available Background Extramedullary relapse (EMR is a recurrence of leukemia in sites other than the bone marrow, and it exhibits a relatively rare presentation of relapse of acute leukemia. However, EMR is an important cause of treatment failure among patients with acute leukemia. Therefore, early detection of these relapses may improve the prognosis. Objectives To describe the disease-related demographic and clinical features and radiologic findings for children diagnosed with EMR in acute leukemia. Patients and Methods The study was based on 22 children (M: F = 14: 8; mean age 7.30 (2.1 - 15.7 years with 8 acute myeloid leukemia (AML and 14 acute lymphoid leukemia (ALL who had experienced an EMR. Age, gender, clinical symptoms, initial extramedullary disease (EMD, French-American-British (FAB morphology, cytogenetics, time to and site of EMR, concurrent bone marrow relapse (BMR, radiologic findings, and outcomes were evaluated. Results No definite relationship was found between initial EMD and EMR. A predilection for AML to relapse in the central nervous system (CNS, except for the CSF and bone, and for ALL to relapse in the CSF and kidney seemed to occur. Patients with EMR had a significantly higher incidence of t(8: 21 cytogenetics and FAB M2 and L1 morphologies. EMR accompanied with concurrent BMR occurred in 31.8% of the patients, who exhibited a relatively grave clinical course. Radiologic findings were nonspecific and had a great variety of structure involved, including bulging enhancing mass in the CT scan, hypoechoic mass in the US, and enhanced mass-like lesion in the MRI. Conclusions Knowledge of the potential sites of EMR, their risk factors, and their clinical and radiologic features may be helpful in the early diagnosis of relapse and planning for therapy.

  8. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  10. Pseudo-Guillain–Barré syndrome masking acute myeloid leukemia relapse: Brief report and review

    Directory of Open Access Journals (Sweden)

    Fadi El Karak

    2015-01-01

    Full Text Available Central nervous system (CNS relapse is not a rare presentation in acute myeloid leukemia (AML as its incidence ranges between 2% and 9%. It manifests with meningeal leukemia, cranial nerve palsies or cerebral mesenchymal myeloid sarcoma. We herein report the case of a 69 year-old female that presented a pseudo-Guillain–Barré syndrome masking an AML CNS relapse. Her symptoms completely resolved upon administration of a tailored treatment. This case suggests that puzzling neurological manifestations in patients with a history of AML should be considered as a CNS recurrence and investigated accordingly even in the context of normal imaging findings.

  11. Isolated extra-medullary relapse of acute leukemia following allogeneic bone marrow transplantation.

    Science.gov (United States)

    Firas, Al Sabty; Demeckova, E; Bojtarova, E; Czako, B; Hrubisko, M; Mistrik, M

    2008-01-01

    Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

  12. 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.

  13. Testicular relapse of acute lymphocytic leukemia: Usefulness of color and power Doppler sonography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwang Hun; Yoon, Choon Sik; Lee, Sung Il; Kim, Myung Joon [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yang, Chang Hyun [Yang Dong Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1999-09-15

    To evaluate the usefulness of color and power Doppler sonography in detecting testicular relapse of leukemia. Both gray- scale and color (power) Doppler ultrasound (US) were performed in seven patients. Two additional patients examined by gray-scale US only were included. The patients were 4-14 years old (mean age, 9 years). Ten tests were confirmed to have leukemic relapse, eight by pathology and two by clinical evidence. Gray-scale US showed variable findings: heterogeneous hypoechogenicity (5) and homogeneous isoechogenicity (5). In all seven patients (8 tests) who underwent both color and power Doppler US, diffuse and marked hypervascularity was demonstrated. One case showed enlarged epididymis with heterogeneous echogenicity, which was the same character as the involved testis. Color and power Doppler US are useful methods in the identification of the testicular relapse of leukemia by demonstrating diffuse, marked hypervascularity in the proper clinical settings.

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

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    Vali A Mehrzad

    2012-01-01

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

  15. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study.

    Science.gov (United States)

    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.

  16. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei

    2012-01-01

    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  17. The contributions of the European Medicines Agency and its pediatric committee to the fight against childhood leukemia

    Directory of Open Access Journals (Sweden)

    Rose K

    2015-11-01

    children with relapsed or refractory disease expose these children to questionable trials, and could undermine public trust in pediatric clinical research. Institutions, investigators, and ethics committees/institutional review boards need to be skeptical of trials triggered by PDCO. New, better ways to facilitate drug development for pediatric leukemia are needed. Keywords: childhood leukemia, better medicines for children, pediatric drug development, therapeutic orphans, therapeutic hostages, ghost studies, pediatric investigation plan

  18. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi;

    2014-01-01

    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...... with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects....

  19. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  20. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  1. GLUCOCORTICOID RECEPTOR IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    YANG Ping; LIAO Qing-kui; LUO Chun-hua

    1999-01-01

    Objective: To investigate the relationship among glucocorticoid receptor (GCR) level, immunological classification and clinical efficacy of chemotherapy in acute lymphoblastic leukemia (ALL) children. Methods: The GCR level of venous blood lymphocytes was measured by receptor radioligand binding assay in 50 cases with childhood ALL and 41 normal children. The immunological classification of 32 children with ALL was analyzed by ABC immunoenzymatic method. Results: The GCR number in venous blood lymphocytes of normal children was 4651±1617 binding sites/cell. The normal range (95%) was 1482-7800 binding sites/cell. The GCR level of 50 cases with ALL (6695±5256 binding sites/cell) was significantly higher than that of the normal ones (t=2.50, P<0.05). The GCR level of the ALL children with good prognosis was significantly higher than that of bad prognosis (t=4.39,P<0.001). The relationship between immunological classification and GCR level of 32 cases with children ALL was as follows: GCR level of T-ALL and B-ALL were significantly lower than AUL, C-ALL and pre-B-ALL; the prognosis of T-ALL and B-ALL was also bad; the GCR level of the group with good prognosis was significantly higher than that with bad prognosis in all immunological types. Conclusion: The GCR level of the peripheral venous blood lymphocytes in children ALL may be an important biochemistry indicator and used to predict prognosis and guide combination chemotherapy. The relationship between GCR and immunological classification can be useful to the expectation of prognosis.

  2. Molecular epidemiology of childhood leukemia with emphasis on chemical exposures

    Energy Technology Data Exchange (ETDEWEB)

    Buffler, P.A.; Smith, M.T.; Wood, S. [Univ. of California, Berkeley, CA (United States); Reynolds, P. [California Dept. of Health Services, Emeryville, CA (United States)

    1996-12-31

    Developing markets in the Pacific Basin depend heavily on the production and export of consumer goods. The generation of hazardous waste as a by-product of industrial production can be linked to adverse health outcomes, such as childhood leukemia, in ways that are presently unknown. In California, exposures resulting from hazardous waste disposal are of concern in the etiology of childhood cancer. Approximately 63% of the 57 hazardous waste sites that the U.S. Environmental Protection Agency (USEPA) included in the national priority list under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) statute were in the six-county San Francisco Bay area. This area includes California`s Silicon Valley, where a disproportionate majority of these sites are located. Although only one study links hazardous waste disposal to childhood leukemia evidence is accumulating that in utero and maternal pesticide exposures as well as chemical exposures during childhood are important in the etiology of childhood leukemia. This study investigates whether children with leukemia have common genetic changes, whether children with genetic changes experience common chemical exposures, and whether the occurrences of these genetic changes correspond to the same temporal sequence as exposure. The purpose of this paper is to describe the study design and report on the status of research activity. 10 refs., 1 fig., 3 tabs.

  3. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.

    Science.gov (United States)

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R; Greipp, Patricia T

    2014-06-01

    The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.

  4. Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient.

    Science.gov (United States)

    Li, Ying; Suo, Shanshan; Mao, Liping; Wang, Lei; Yang, Chunmei; Xu, Weilai; Lou, Yinjun; Mai, Wenyuan

    2015-01-01

    In the clinical setting, bleeding is a common manifestation of acute promyelocytic leukemia (APL), whereas thrombosis is relatively rare, especially as an initial symptom. Here, we report an unusual case of APL with acute myocardial infarction as the first manifestation and cerebral infarction as the relapse manifestation in a healthy young woman. This unique case emphasizes that a thrombotic event could be the first manifestation of an underlying hematological disorder such as APL and could also be a sign of relapse. Rapid detection of the underlying disorder and the timely use of anticoagulation therapy and ATRA are crucial for preventing further deterioration of the disease and saving the patient's life.

  5. 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.

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

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

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

  7. Childhood leukemia and residential proximity to industrial and urban sites

    Energy Technology Data Exchange (ETDEWEB)

    García-Pérez, Javier, E-mail: jgarcia@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); López-Abente, Gonzalo, E-mail: glabente@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); Gómez-Barroso, Diana, E-mail: dgomez@externos.isciii.es [CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); Morales-Piga, Antonio, E-mail: amorales@isciii.es [Rare Disease Research Institute (IIER), Carlos III Institute of Health, Madrid (Spain); Consortium for Biomedical Research in Rare Diseases (CIBERER), Madrid (Spain); Pardo Romaguera, Elena, E-mail: elena.pardo@uv.es [Spanish Registry of Childhood Tumors (RETI-SEHOP), University of Valencia, Valencia (Spain); Tamayo, Ibon, E-mail: ibontama@gmail.com [Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, Donostia (Spain); Fernández-Navarro, Pablo, E-mail: pfernandezn@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  8. 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...

  9. What Are the Risk Factors for Childhood Leukemia?

    Science.gov (United States)

    ... for a possible link to childhood leukemia include: Exposure to electromagnetic fields (such as living near power lines) Living near a nuclear power plant Infections early in life Mother’s age when child is ... history Fetal exposure to hormones such as diethylstilbestrol (DES) or birth ...

  10. Impact of high electromagnetic field levels on childhood leukemia incidence

    NARCIS (Netherlands)

    Teepen, J.C.; Dijck, J.A. van

    2012-01-01

    The increasing exposure to electromagnetic fields (EMFs) has raised concern, as increased exposure may result in an increased risk of childhood leukemia (CL). Besides a short introduction of CL and EMF, our article gives an evaluation of the evidence of a causal relation between EMF and CL by critic

  11. 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...

  12. Pediatric T-lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

    DEFF Research Database (Denmark)

    Kunz, Joachim B; Rausch, Tobias; Bandapalli, Obul R;

    2015-01-01

    and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. In relapse compared to primary T-cell acute lymphoblastic leukemia, the number of single nucleotide variants and small insertions and deletions approximately...... doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, type 1 relapse derives from the primary...

  13. 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......--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets...

  14. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

    Directory of Open Access Journals (Sweden)

    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  15. 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.

  16. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nestor R. Ramos

    2015-04-01

    Full Text Available The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

  17. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Science.gov (United States)

    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  18. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

    Science.gov (United States)

    Mody, Mayur D; Ravindranathan, Deepak; Gill, Harpaul S; Kota, Vamsi K

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  19. 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.

  20. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  1. Isolated testicular relapse in acute lymphoblastic leukemia - Effective treatment with the modified CCG-112 protocol

    Directory of Open Access Journals (Sweden)

    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.

  2. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.

    Science.gov (United States)

    Garg, Manoj; Nagata, Yasunobu; Kanojia, Deepika; Mayakonda, Anand; Yoshida, Kenichi; Haridas Keloth, Sreya; Zang, Zhi Jiang; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ding, Ling-Wen; Alpermann, Tamara; Sun, Qiao-Yang; Lin, De-Chen; Chien, Wenwen; Madan, Vikas; Liu, Li-Zhen; Tan, Kar-Tong; Sampath, Abhishek; Venkatesan, Subhashree; Inokuchi, Koiti; Wakita, Satoshi; Yamaguchi, Hiroki; Chng, Wee Joo; Kham, Shirley-Kow Yin; Yeoh, Allen Eng-Juh; Sanada, Masashi; Schiller, Joanna; Kreuzer, Karl-Anton; Kornblau, Steven M; Kantarjian, Hagop M; Haferlach, Torsten; Lill, Michael; Kuo, Ming-Chung; Shih, Lee-Yung; Blau, Igor-Wolfgang; Blau, Olga; Yang, Henry; Ogawa, Seishi; Koeffler, H Phillip

    2015-11-26

    Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone.

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

    Directory of Open Access Journals (Sweden)

    Bekker-Méndez Vilma

    2011-08-01

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

  4. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

    Directory of Open Access Journals (Sweden)

    Elisa Dorantes-Acosta

    2013-01-01

    Full Text Available Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

  5. Osteogenic toxicity in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet)

    2013-01-01

    textabstractBone mineral density (BMD) Our multi-center study in children treated according to the Dutch Childhood Oncology Group (DCOG)-ALL9 protocol showed a three-years cumulative incidence of fractures of 18%. BMD of ALL patients was lower than of healthy peers. The year after treatment disconti

  6. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-31

    Acute Leukemia of Ambiguous Lineage; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

    Directory of Open Access Journals (Sweden)

    Emmons Gregory S

    2012-10-01

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

  8. Acute Myeloid Leukemia Relapse Presenting as Complete Monocular Vision Loss due to Optic Nerve Involvement

    Directory of Open Access Journals (Sweden)

    Shyam A. Patel

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity. Cerebrospinal fluid (CSF analysis showed a total WBC count of 81/mcl with 96% AML blasts. The onset and progression of visual loss were in concordance with rise in peripheral blood blast count. A low threshold for diagnosis of CSF involvement should be maintained in patients with hyperleukocytosis and high-risk cytogenetics so that prompt treatment with whole brain radiation and intrathecal chemotherapy can be delivered. This case suggests that the eye, as an immunoprivileged site, may serve as a sanctuary from which leukemic cells can resurge and contribute to relapsed disease in patients with high-risk cytogenetics.

  9. Parental and infant characteristics and childhood leukemia in Minnesota

    Directory of Open Access Journals (Sweden)

    Ross Julie A

    2008-02-01

    Full Text Available Abstract Background Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL, few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology. Methods We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR and 95% confidence intervals (CIs. Results Male sex (HR = 1.41, 95% CI 1.16–1.70, white race (HR = 2.32, 95% CI 1.13–4.76, and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70 increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47. Higher birth weights (>3798 grams (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65, and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60 increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education. Conclusion We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.

  10. Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fuchs Mary

    2012-08-01

    Full Text Available Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.

  11. FCR and Bevacizumab (FCR-B) Treatment in Patients with Relapsed Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    Jain, Preetesh; Lee, Hun Ju; Qiao, Wei; Wierda, William; Benjamini, Ohad; Burger, Jan; Ferrajoli, Alessandra; Estrov, Zeev; Kantarjian, Hagop; Keating, Michael; O’Brien, Susan

    2014-01-01

    Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of pro-angiogenic growth factors such as VEGF and/or angiopoietin-2 (Ang-2) are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A. In this study, we analysed whether a combination of bevacizumab (B) with FCR chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31–84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity and 57 were evaluable for response. Six cycles were planned; 36 (59%) patients completed ≥ 4–6 cycles of the regimen. The overall response rate (ORR) was 79% with 13 (23%) complete remissions (CR), 8 (14%) nodular partial remissions (nPR) and 24 (43%) partial remissions (PR). The median progression free survival (PFS) and overall survival (OS) rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n=40), infections (n=21), thrombocytopenia (n=18) and anemia (n=9). Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR. PMID:25043749

  12. Combination of Cladribine plus Topotecan for Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Inaba, Hiroto; Stewart, Clinton F.; Crews, Kristine R.; Yang, Shengping; Pounds, Stanley; Pui, Ching-Hon; Rubnitz, Jeffrey E.; Razzouk, Bassem I.; Ribeiro, Raul C.

    2009-01-01

    BACKGROUND The prognosis after relapse of pediatric acute myeloid leukemia (AML) is poor and effective salvage regimens are urgently needed. METHODS In Phase I and pilot studies, we evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a 5-day course of cladribine (2-CDA) followed by topotecan in pediatric patients with relapsed/refractory AML. The 2-CDA dose was escalated as follows: 9.1, 13.6, 16.3, and 19.5 mg/m2 per day (8.9 mg/m2 per day in the pilot study). Outcome was analyzed according to the absence (stratum 1) vs. presence (stratum 2) of previous allogeneic hematopoietic stem cell transplantation. Twenty-six patients (20 in stratum 1, 6 in stratum 2) were treated. RESULTS The MTD was not reached in stratum 1, but DLT occurred at the lowest 2-CDA dosage (9.1 mg/m2 per day) in stratum 2. Febrile neutropenia was common in both strata. Nine (34.6%) of 26 patients experienced a complete response and 7 (30.4%) had a partial response; 5 (19.2%) are long-term survivors. Clinical outcome was not associated with 2-CDA or topotecan systemic exposure. CONCLUSION The combination was well tolerated in stratum 1, and the response rate is encouraging. This regimen offers a post-relapse treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy. PMID:19885837

  13. Epidemiology of childhood leukemia in the presence and absence of Down syndrome.

    Science.gov (United States)

    Mezei, Gabor; Sudan, Madhuri; Izraeli, Shai; Kheifets, Leeka

    2014-10-01

    Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.

  14. 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.

  15. Distance from residence to power line and risk of childhood leukemia

    DEFF Research Database (Denmark)

    Pedersen, Camilla; Raaschou-Nielsen, Ole; Rod, Naja Hulvej

    2013-01-01

    Epidemiological studies have found an association between exposure to extremely low-frequency magnetic fields (ELF-MF) and childhood leukemia. In 2005, a large British study showed an association between proximity of residence to high-voltage power lines and the risk of childhood leukemia...

  16. Maternal and perinatal risk factors for childhood leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Zack, M.; Adami, H.O.; Ericson, A. (Centers for Disease Control, Atlanta, GA (USA))

    1991-07-15

    This report describes an exploratory population-based study of maternal and perinatal risk factors for childhood leukemia in Sweden. The Swedish National Cancer Registry ascertained 411 cases in successive birth cohorts from 1973 through 1984 recorded in the Swedish Medical Birth Registry. Using the latter, we matched five controls without cancer to each case by sex and month and year of birth. Mothers of children with leukemia were more likely to have been exposed to nitrous oxide anesthesia during delivery than mothers of controls (odds ratio (OR) = 1.3; 95% confidence interval (CI) = 1.0, 1.6). Children with leukemia were more likely than controls to have Down's syndrome (OR = 32.5; 95% CI = 7.3, 144.0) or cleft lip or cleft palate (OR = 5.0; 95% CI = 1.0, 24.8); to have had a diagnosis associated with difficult labor but unspecified complications (OR = 4.5; 95% CI = 1.1, 18.2) or with other conditions of the fetus or newborn (OR = 1.5; 95% CI = 1.1, 2.1), specifically, uncomplicated physiological jaundice (OR = 1.9; 95% CI = 1.2, 2.9); or to have received supplemental oxygen (OR = 2.6; 95% CI = 1.3, 1.3, 4.9). Because multiple potential risk factors were analyzed in this study, future studies need to check these findings. The authors did not confirm the previously reported higher risks for childhood leukemia associated with being male, having a high birth weight, or being born to a woman of advanced maternal age.

  17. Nonmyeloablative Allogeneic Stem Cell Transplantation in Relapsed/Refractory Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Khouri, Issa F.; Bassett, Roland; Poindexter, Nancy; O'Brien, Susan; Bueso-Ramos, Carlos E.; Hsu, Yvonne; Ferrajoli, Alessandra; Keating, Michael J.; Champlin, Richard; Fernandez-Vina, Marcelo

    2015-01-01

    BACKGROUND The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chronic lymphocytic leukemia (CLL) is not well established. The authors report on long-term experience with NST in relapsed/refractory CLL and define prognostic factors associated with outcome. METHODS The authors reviewed the outcome of 86 patients with relapsed/relapsed CLL enrolled in sequential NST protocols. RESULTS The median patient age was 58 years. Patients were heavily pretreated before transplantation, and 43 required immunomanipulation after NST for persistent or recurrent disease. Immunomanipulation included withdrawal of immunosuppression, rituximab, and step-wise donor lymphocyte infusions. Of 43 patients receiving immunomanipulation, 20 (47%) experienced a complete remission. Patients with human leukocyte antigen (HLA) genotype A1+/A2−/B44− were more likely to experience a complete remission (P ¼ .0009), with rates of 9%, 36%, 50%, and 91%, respectively, for 0, 1, 2, and 3 of these HLA factors. This resulted in significant improvement in progression-free-survival rates of 68.2% at 5 years for patients with all 3 HLA factors. Overall, the estimated 5-year survival rate was 51%. In a multivariate model, a CD4 count of <100/mm3 and a below normal serum immunoglobulin G level at study entry were associated with a short survival duration (P < .0001). CONCLUSIONS These results confirm the potential cure of relapsed/refractory CLL with NST and provide the first evidence that immunoglobulin G and CD4 levels are predictive of overall survival after NST in CLL and that human leukocyte antigen alleles predict response to immunomanipulation. PMID:21455998

  18. Clinical Effect of Total Body Irradiation and Hematopoietic Stem Cell Transplantation for Refractory and Relapsed Childhood Leukemia%含全身照射方案的造血干细胞移植对难治性白血病的疗效

    Institute of Scientific and Technical Information of China (English)

    陈点点; 郭智; 冯超英; 路娜; 王雅棣

    2013-01-01

    Objective To explore the efficacy and feasibility of allogeneic hematopoietic stem cell transplantation ( allo-HSCT) and total body irradiation (TBI) for refractory and relapsed leukemia. Methods 20 patients with refractory and relapsed leukemia who received allo -HSCT were examined. Bone marrow combined with peripheral blood HSCT was used . All patients were treated with standardized conditioning regimen consisting of cytarabine , busulfan, fludarabine and TBI ,etc. Body irradiation used 6MV-X irradiation. Graft-versus-host disease ( GVHD) prophylaxis used classic cyclosporin A , methotrexate ,anti-thymocyte immu-noglobulin and CD25 monoclonal antibody. Complications and disease-free survival after transplantation of patients were observed . Results All of the patients were engrafted and had 100% donor hematological cell after transplantation by cytogenetic evidence analysis. Patients have mild symptoms such as nausea ,vomiting,parotid swelling,no case of interstitial pneumonia after TBI. The median follow up time was 12.5 months (6 ~36 months).8 cases had experience of GVHD ,2 died of acute GVHD ,2 died of infection and 6 died of relapse. The rest 10 patients were alive in free situation and the disease -free survival rates at 2 years were 50%. Conclusion Hematopoietic stem cell transplantation combined with total body irradiation program is safe and effective treatment for refractory and relapsed leukemia. It can be widely used in clinical as a key technology for salvage therapy .%目的 探讨含全身照射(TBI) 预处理方案的造血干细胞移植(allo-HSCT)对难治性白血病的疗效和安全性.方法 采用含TBI预处理方案的allo-HSCT治疗20例难治性白血病患者,采用骨髓加外周血干细胞联合移植,预处理方案包括阿糖胞苷、氟达拉滨及TBI等,全身照射采用6MV-X照射,移植物抗宿主病(GVHD) 预防采用经典环孢菌素A(CSA) 和氨甲蝶呤(MTX)及抗胸腺细胞免疫球蛋白(ATG)、CD25单克隆抗体,

  19. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-09-12

    Chimerism; Hematopoietic Cell Transplantation Recipient; Previously Treated Myelodysplastic Syndrome; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia.

    Science.gov (United States)

    Gibson, Todd M; Ehrhardt, Matthew J; Ness, Kirsten K

    2016-04-01

    Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

  1. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  2. Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

    Science.gov (United States)

    Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía; Roman, Eve; Schüz, Joachim; Magnani, Corrado; Mora, Ana Maria; Mueller, Beth A; de Oliveira, Maria S Pombo; Dockerty, John D; McCauley, Kathryn; Lightfoot, Tracy; Hatzipantelis, Emmanouel; Rudant, Jérémie; Flores-Lujano, Janet; Kaatsch, Peter; Miligi, Lucia; Wesseling, Catharina; Doody, David R; Moschovi, Maria; Orsi, Laurent; Mattioli, Stefano; Selvin, Steve; Kang, Alice Y; Clavel, Jacqueline

    2016-08-15

    The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.

  3. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-05-05

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  4. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-12-03

    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 Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  5. Therapy-induced secondary acute myeloid leukemia with t(11;19)(q23;p13.1) in a pediatric patient with relapsed acute promyelocytic leukemia.

    Science.gov (United States)

    Dang, Daniel N; Morris, Heather D; Feusner, James H; Koduru, Prasad; Wilson, Kathleen; Timmons, Charles F; Cavalier, MaryEllen; Luu, Hung S

    2014-11-01

    Acute myeloid leukemia is classified based upon recurrent cytogenetic abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia (APL). The translocation results in fusion of the retinoic acid receptor-α (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1. Standard APL therapy is a combination of all-trans retinoic acid and anthracycline-based chemotherapy. Anthracycline treatment is associated with secondary clonal chromosomal aberrations that can lead to therapy-related secondary myeloid neoplasms. We present a pediatric case of relapsed APL coexistent with treatment-associated secondary myeloid neoplasm with t(11;19)(q23;p13.1).

  6. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  7. Kidney and Pancreatic Extramedullary Relapse in Adult Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Leslie Skeith

    2013-01-01

    Full Text Available Extramedullary relapse of acute lymphoblastic leukemia (ALL is rare and has been primarily reported in pediatric patients or hematopoietic stem cell transplant recipients. We report a case of a 62-year-old woman who presented with relapsed ALL involving her kidneys, pancreas, and bone marrow 2 years after completing chemotherapy with a standard ALL protocol. Unfortunately, her extramedullary disease progressed despite treatment. To the best of our knowledge, this is the first reported case of extramedullary relapse of B-cell ALL to the kidneys and pancreas occurring in an adult patient who had not previously undergone a hematopoietic stem cell transplant. A literature review of kidney and pancreatic extramedullary relapse in ALL is also included.

  8. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  9. 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

  10. Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.

    Science.gov (United States)

    Bailey, Helen D; Fritschi, Lin; Infante-Rivard, Claire; Glass, Deborah C; Miligi, Lucia; Dockerty, John D; Lightfoot, Tracy; Clavel, Jacqueline; Roman, Eve; Spector, Logan G; Kaatsch, Peter; Metayer, Catherine; Magnani, Corrado; Milne, Elizabeth; Polychronopoulou, Sophia; Simpson, Jill; Rudant, Jérémie; Sidi, Vasiliki; Rondelli, Roberto; Orsi, Laurent; Kang, Alice Y; Petridou, Eleni; Schüz, Joachim

    2014-11-01

    Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.

  11. Commentary on "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations"

    Science.gov (United States)

    Schmitt, Ara

    2011-01-01

    This commentary pertains to the article, "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations" by D. Scott Hermann, Jill R. Thurber, Kenneth Miles, and Gloria Gilbert in this issue (2011) regarding pediatric leukemia. The authors present a literature review regarding leukemia in childhood,…

  12. Study of Safety,Efficacy and Pharmacokinetics of CT-1530 in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

    Science.gov (United States)

    2016-12-01

    Relapsed or Refractory B Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Waldenstrom's Macroglobulinemia; Mantle Zone Lymphoma Refractory/Recurrent; Follicle Centre Lymphoma Diffuse; Diffuse Large B Cell Lymphoma

  13. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  14. 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...... 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 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...

  15. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

    Science.gov (United States)

    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo

    2005-08-15

    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  16. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  17. 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

  18. Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

    Institute of Scientific and Technical Information of China (English)

    Guogen Mao; Fenghua Yuan; Kimberly Absher; C Darrell Jennings; Dianna S Howard; Craig T Jordan; Liya Gu

    2008-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.

  19. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: case report and literature review.

    Science.gov (United States)

    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.

  20. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Lee, Bang-Ning; Schlette, Ellen J; O'Brien, Susan M; Gao, Hui; Wen, Sijin; Wierda, William G; Estrov, Zeev; Faderl, Stefan; Cohen, Evan N; Li, Changping; Reuben, James M; Keating, Michael J

    2008-06-01

    This study investigated the activity of lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Lenalidomide was given at 10 mg daily with dose escalation up to 25 mg daily. Three patients (7%) achieved a complete response (CR), one a nodular partial remission, and 10 patients a partial remission (PR), for an overall response (OR) rate of 32%. Treatment with lenalidomide was associated with an OR rate of 31% in patients with 11q or 17p deletion, of 24% in patients with unmutated V(H), and of 25% in patients with fludarabine-refractory disease. The most common toxicity was myelosuppression, and the median daily dose of lenalidomide tolerated was 10 mg. Plasma levels of angiogenic factors, inflammatory cytokines, and cytokine receptors were measured at baseline, day 7, and day 28. There was a dramatic increase in median interleukin (IL)-6, IL-10, IL-2, and tumor necrosis factor receptor-1 levels on day 7, whereas no changes were observed in median vascular endothelial growth factor levels (20 patients studied). According to our experience, lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL.

  1. Cerebral embolism through hematogenous dissemination of pulmonary mucormycosis complicating relapsed leukemia.

    Science.gov (United States)

    Higo, Takashi; Kobayashi, Takashi; Yamazaki, Sho; Ando, Sumiyo; Gonoi, Wataru; Ishida, Masanori; Okuma, Hidemi; Nakamura, Fumihiko; Ushiku, Tetsuo; Ohtomo, Kuni; Fukayama, Masashi; Kurokawa, Mineo

    2015-01-01

    Invasive mucormycosis in patients with hematological diseases mostly occurs in the lungs. Invasive mucormycosis of other anatomical sites is relatively infrequent and its pathogenesis has not so far been well elucidated. Here, we describe an autopsy case of pulmonary invasive mucormycosis complicated by cerebral embolism with infarct. A 77-year-old Japanese woman with relapsed acute myeloid leukemia complained of left visual disturbance and weakness of the lower limbs. The diagnosis of leukemic infiltration to the central nervous system was made. Repeated intrathecal injection of methotrexate plus cytarabine resulted in partial amelioration of the neurologic symptoms. However, the patient then developed fever, dyspnea, and subsequent right hemiparesis. A computed tomography (CT) scan showed a consolidative shadow with halo sign in the left lung field, which was compatible with either invasive pulmonary aspergillosis or mucormycosis. These findings accounted for fever and dyspnea, but not hemiparesis. Despite antifungal therapy, the patient succumbed to death after two weeks. Autopsy revealed pulmonary invasive mucormycosis with a fungal ball in the lumina of the adjacent ascending aorta. Intriguingly, autopsy and postmortem CT scan identified left cerebral infarct due to mucormycosis, which accounted for the right hemiparesis. It is likely that the fungal ball caused the cerebral embolism through hematogenous dissemination. We should suspect hematogenous dissemination when we see a patient with pulmonary invasive mucormycosis developing neurologic symptoms.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

  3. Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations

    Science.gov (United States)

    Herrmann, D. Scott; Thurber, Jill R.; Miles, Kenneth; Gilbert, Gloria

    2011-01-01

    Leukemias (blood cell cancers) and central nervous system tumors are the most frequently occurring types of cancer in children. Mortality rates from all childhood cancers have decreased over the past 2 decades. As a result, many childhood cancer survivors are now returning to their schools after having been successfully treated. Although most of…

  4. RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

    Science.gov (United States)

    Gianfelici, Valentina; Chiaretti, Sabina; Demeyer, Sofie; Di Giacomo, Filomena; Messina, Monica; La Starza, Roberta; Peragine, Nadia; Paoloni, Francesca; Geerdens, Ellen; Pierini, Valentina; Elia, Loredana; Mancini, Marco; De Propris, Maria Stefania; Apicella, Valerio; Gaidano, Gianluca; Testi, Anna Maria; Vitale, Antonella; Vignetti, Marco; Mecucci, Cristina; Guarini, Anna; Cools, Jan; Foà, Robin

    2016-01-01

    Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways. PMID:27151993

  5. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.

    Science.gov (United States)

    Douer, D; Estey, E; Santillana, S; Bennett, J M; Lopez-Bernstein, G; Boehm, K; Williams, T

    2001-01-01

    A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.

  6. 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

  7. Combination of arsenicum trioxide and all trans retinoic acid in the treatment of relapsed acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    A. N. Sokolov

    2015-01-01

    Full Text Available From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL (median age – 30 years received arsenicum trioxide (ATO. ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA (1 patient – from day 29 of ATO therapy. Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT, 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission. 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months, 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Elvis Terci Valera

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

  10. Steinmaus and Smith Respond to "Proximity to Gasoline Stations and Childhood Leukemia".

    Science.gov (United States)

    Steinmaus, Craig; Smith, Martyn T

    2017-01-01

    Benzene is an established cause of adult leukemia, but its role in childhood leukemia is less clear. In a recent meta-analysis, we identified associations of childhood leukemia with occupational and household product benzene exposure and traffic-related pollution. Residential proximity to gasoline stations or automobile repair facilities may be another source of benzene, and in 3 studies assessing these sources, we identified a summary relative risk of 1.59 (95% confidence interval: 0.70, 3.62). Although not statistically significant, this summary relative risk was of a magnitude similar to that of our other positive findings. In this issue of the Journal (Am J Epidemiol 2017;185(1):5-7), Dr. Infante suggested that meta-analyses of studies on childhood leukemia and proximity to gasoline stations should involve some criteria that differ from those we used. These suggested criteria involved combining leukemia subtypes, excluding automobile repair facilities, and using nonleukemia cancers as control subjects. We redid our meta-analysis using these new criteria and obtained a summary relative risk of 2.42 (95% confidence interval: 1.51, 3.89). Overall, although this result should be interpreted in light of the relatively small sample size (3 studies) and its post-hoc nature, it provides additional new evidence for associations of childhood leukemia with both residential proximity to gasoline stations and exposure to benzene.

  11. Very late recurrences of leukemia: why does leukemia awake after many years of dormancy?

    Science.gov (United States)

    Norkin, Maxim; Uberti, Joseph P; Schiffer, Charles A

    2011-02-01

    We report a heterogeneous group of very late recurrences of leukemia occurring more than 10 years after initial treatment including 2 cases of childhood acute lymphoblastic leukemia (ALL) which recurred after more than 20 years of remission, 2 cases of donor cell leukemia which developed more than 10 years after allograft for acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) and 2 cases of chronic myeloid leukemia (CML) relapsing 13 and 17 years after allograft. Case descriptions are followed by a discussion regarding possible mechanisms leading to leukemia recurrence and a review of the literature.

  12. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  13. Early loss of teeth after treatment for childhood leukemia; Fruehzeitiger Zahnverlust nach Leukaemiebehandlung im Kindesalter. Fallbericht und Literaturuebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, T.; Doerr, W.; Lesche, A.; Lehmann, D. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Medizinische Fakultaet der Technischen Univ. Dresden (Germany); Koy, S. [Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie, Medizinische Fakultaet der Technischen Univ. Dresden (Germany)

    2004-06-01

    Background: only few reports of effects of radiotherapy in childhood on the dental apparatus are available in the literature. The basis for early loss of teeth appears to be a reduction of the root surface area after radiation exposure. These effects in the periodontium are a consequence of combined radiochemotherapy usually applied for treatment of childhood neoplasia. Chemotherapy alone also results in changes of periodontal development. Case report: a 33-year-old patient is reported, who, at the age of 11 years, received high-dose chemotherapy and radiotherapy of neuroaxis and cranium for acute lymphatic leukemia with relapse. The patient consulted the Implant Section of the Department of Oral and Maxillofacial Surgery because of severe dental changes and tooth loss despite adequate dental care and oral hygiene. Radiation doses given to the superior maxilla and mandible at the age of 11 were estimated to be in the range of 8-25 Gy. Conclusion: intense, life-long dental care and follow-up of patients cured from malignant disease in childhood must hence be postulated in order to minimize dental treatment sequelae by supportive measures, but also to initiate timely adequate dental and prosthetic management. (orig.)

  14. Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance.

    Directory of Open Access Journals (Sweden)

    Ezhilarasi Chendamarai

    Full Text Available There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL in comparison with newly diagnosed cases (NAPL. We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022. The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38% of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92, cell survival (n=50, immune regulation (n=74 and stem cell regulation (n=51. Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001 in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.

  15. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Burke, Michael J; Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Ghodke-Puranik, Yogita; Lindgren, Bruce R; Weigel, Brenda J; Verneris, Michael R; Miller, Jeffrey S

    2014-09-01

    DNA hypermethylation and histone deacetylation are pathways of leukemia resistance. We investigated the tolerability and efficacy of decitabine and vorinostat plus chemotherapy in relapse/refractory acute lymphoblastic leukemia (ALL). Decitabine (15 mg/m(2) iv) and vorinostat (230 mg/m(2) PO div BID) were given days 1-4 followed by vincristine, prednisone, PEG-asparaginase, and doxorubicin. Genome wide methylation profiles were performed in 8 matched patient bone marrow (BM) samples taken at day 0 and day 5 (postdecitabine). The median age was 16 (range, 3-54) years. All patients had a prior BM relapse, with five relapsing after allogeneic transplant. The most common nonhematological toxicities possibly related to decitabine or vorinostat were infection with neutropenia (grade 3; n = 4) and fever/neutropenia (grade 3, n = 4; grade 4, n = 1). Of the 13 eligible patients, four achieved complete remission without platelet recovery (CRp), two partial response (PR), one stable disease (SD), one progressive disease (PD), two deaths on study and three patients who did not have end of therapy disease evaluations for an overall response rate of 46.2% (CRp + PR). Following decitabine, significant genome-wide hypo-methylation was observed. Comparison of clinical responders with nonresponders identified methylation profiles of clinical and biological relevance. Decitabine and vorinostat followed by re-Induction chemotherapy was tolerable and demonstrated clinical benefit in relapsed patients with ALL. Methylation differences were identified between responders and nonresponders indicating interpatient variation, which could impact clinical outcome. This study was registered at www.clinicaltrials.gov as NCT00882206.

  16. Commentary on "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations"

    Science.gov (United States)

    Schmitt, Ara

    2011-01-01

    This commentary pertains to the article, "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations" by D. Scott Hermann, Jill R. Thurber, Kenneth Miles, and Gloria Gilbert in this issue (2011) regarding pediatric leukemia. The authors present a literature review regarding leukemia in…

  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. Birth Weight and Acute Childhood Leukemia: A Meta-analysis of Observational Studies

    Science.gov (United States)

    2007-11-02

    neurofibromatosis, Shwachman syndrome, Bloom syndrome, ataxia telangiectasia, Langerhans cell histiocytosis, and Klinefelter syndrome Increased...childhood leukemia (both ALL and AML) with maternal history of fetal loss14-16 while one study reported an inverse association.17 Some studies showed...about 1.5 times).124 There is little current insight into the natural history of acute leukemia in children and the likely timing of key

  19. Psychosocial aspects of survivors of childhood cancer or leukemia.

    Science.gov (United States)

    Massimo, L; Zarri, D; Caprino, D

    2005-12-01

    The majority of childhood cancer patients can expect nowadays to be cured and the percentage is now between 70% and 80%. The number of long-term survivors, off- threatment for at least 5 years, is rising rapidly and is becoming a new population, which needs a special care. It is becoming increasingly important to know how to prevent and treat the physical late effects as well as the psychosocial ones. The oldest among these patients are now in their 40's. How will their old age be like? Are they really cured? The aim of this study is to present a detailed survey of the literature on this topic as well as the authors' personal experience. Several techniques of psychological investigation for this population are highlighted. The semistructured interviews are mostly used for mono-institutional research, while the narrative dialogues are useful for small groups of patients. Questionnaires are usually conducted by epidemiologists for large groups of survivors. Tests are used for specific items such as defense mechanisms, self-esteem, relationships within the family, fear, and panic. The evaluation of the post-traumatic stress disorder is considered and the most important literature data are reported. It is also stressed the need of prevention of any type of psychosocial distress. In conclusion, most of the survivors appear to lead normal adult lives, to have obtained high school degrees, good jobs, and several have families and children. Nevertheless, a small percentage show some psychological or social problems, such as anxiety, depression, fear over the future or over relapse, a second primary, or sterility. The most vulnerable among them are females, people in poor financial conditions, the unemployed and those with poor educations.

  20. Molecular and epidemiologic findings of childhood acute leukemia in Costa Rica.

    Science.gov (United States)

    Santamaría-Quesada, Carlos; Vargas, Mario; Venegas, Patricia; Calvo, Melvin; Obando, Catalina; Valverde, Berta; Cartín, Walter; Carrillo, Juan Manuel; Jimenez, Rafael; González, Marcos

    2009-02-01

    In Central America, nearly 70% of pediatric cancer is related to hemato-oncologic disorders, especially acute lymphoblastic leukemia (ALL). Preliminary studies have described a high incidence of childhood leukemia in these countries; however, no molecular analyses of these malignancies have yet been carried out. We studied diagnostic samples from 84 patients from the National Children's Hospital in San Jose, Costa Rica (65 precursor B-ALL, 5 T-cell ALL, and 14 acute myeloblastic leukemia). Our methodology included cytogenetic, fluorescent in situ hybridization, and polymerase chain reaction approaches. The observed rate of leukemia was 52.2 cases per million children per year. Twelve out of 65 (18.4%) precursor B-ALL tested positive for TEL-AML1 and 3 cases for BCR-ABL (4.6%). In addition, we detected 2 patients carrying an E2A-PBX1 transcript (3.1%) and 1 patient with an MLL-AF4 fusion gene (1.5%). None of the T-cell ALL cases were positive for either SIL-TAL1 or HOX11L2. Within 14 acute myeloblastic leukemia patients, we confirmed 2 cases with FLT3-internal tandem duplication+, 1 patient with AML1-ETO, and only 1 case carrying a PML-RARalpha rearrangement. The present study confirms the relatively high incidence of pediatric leukemia in Costa Rica and constitutes the first report regarding the incidence of the main molecular alterations of childhood leukemia in our region.

  1. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    Science.gov (United States)

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  2. Prognostic value of MRD-dynamics in childhood acute lymphoblastic leukemia treated according to the MB-2002/2008 protocols.

    Science.gov (United States)

    Meleshko, Alexander N; Savva, Natalia N; Fedasenka, Uladzimir U; Romancova, Alexandra S; Krasko, Olga V; Eckert, Cornelia; von Stackelberg, Arend; Aleinikova, Olga V

    2011-10-01

    Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT). MRD positivity, as well as quantitative level of MRD were analyzed and compared between patients who stayed in remission and relapsed. Relapse-free survival revealed to be significantly associated with MRD levels at different time points. Unfavorable prognosis was shown for MRD≥10(-3) on day 36 (pPCR in children with ALL treated with ALL-MB protocols is feasible and independently associated with outcome. MRD may be a suitable parameter for treatment stratification in MB protocols in future.

  3. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia

    OpenAIRE

    Robien, Kim; Ness, Kirsten K.; Klesges, Lisa M.; Baker, K. Scott; Gurney, James G.

    2008-01-01

    Recent studies indicate that survivors of childhood acute lymphocytic 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 WCRF/AICR Cancer Prevention recommendations, the DASH diet, and the 2005 USDA Food Guide. Mean daily energ...

  4. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  5. Clinicopathological features of acute promyelocytic leukemia: an experience in one institute emphasizing the morphological and immunophenotypic changes at the time of relapse.

    Science.gov (United States)

    Yoshii, Miyuki; Ishida, Mitsuaki; Yoshida, Takashi; Okuno, Hiroko; Nakanishi, Ryota; Horinouchi, Akiko; Hodohara, Keiko; Okabe, Hidetoshi

    2013-01-01

    Acute promyelocytic leukemia (APL) has two morphological variants, namely macrogranular (M3) and microgranular (M3v). M3v, characterized by the presence of neoplastic promyelocytes with only sparse fine azurophilic granules, accounts for 10-25% of all APL and has unique biological characteristics. Relapse occurs in approximately 20% of patients with APL. The morphological type of the leukemic cells at relapse is usually identical with the primary disease, and only one case of morphological change at relapse has been reported. Here, we analyzed the clinicopathological features of APL, including 4 relapsed cases emphasizing morphological changes at the time of relapse. The unique finding of the present study is that 2 of 4 relapsed cases changed from M3 to M3v at relapse. The morphological features of these were different in each case (one had blastic features and the other resembled monocytoid leukemic cells). Cytogenetic analyses revealed the continued presence of t(15;17)(q22;q12) at the time of relapse and morphological change. Moreover, the immune phenotype of the leukemic cells changed from CD2(-)/CD34(-) to CD2(+)/CD34(+) at that time. These findings suggest that morphological change at relapse in APL may not be a rare event, and that the leukemic cells can show variable morphological features at the time of relapse, which could result in misdiagnosis as a different type of acute myeloid leukemia. Therefore, a comprehensive approach with emphasis on combined morphological, immunophenotypic, and cytogenetic analyses is important for diagnosis and appropriate treatment of relapsed APL.

  6. Supportive care for children with acute leukemia - Report of a survey on supportive care by the Dutch Childhood Leukemia Study Group. Part I

    NARCIS (Netherlands)

    Postma, A; Van Leeuwen, EF; Gerritsen, EJA; Roord, JJ; De vries-Hospers, HG

    1998-01-01

    The Dutch Childhood Leukemia Study Group celebrated its 20th anniversary by conducting a nationwide survey on supportive care for children with leukemia. Pediatricians were asked about daily practice and current perceptions with regard to supportive care. The results are discussed and compared to re

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

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  8. Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in chronic myeloid leukemia patients.

    Science.gov (United States)

    Smirnikhina, Svetlana A; Lavrov, Alexander V; Chelysheva, Ekaterina Yu; Adilgereeva, Elmira P; Shukhov, Oleg A; Turkina, Anna; Kutsev, Sergey I

    2016-07-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease well treated by tyrosine kinase inhibitors (TKIs). The aim was to identify genes with a predictive value for relapse-free survival after TKI cessation in CML patients. We performed whole-exome sequencing of DNA from six CML patients in long-lasting deep molecular remission. Patients were divided into two groups with relapse (n = 3) and without relapse (n = 3) after TKI discontinuation. We found variants in genes CYP1B1, ALPK2, and IRF1 in group of patients with relapse and one variant in gene PARP9 in group of patients without relapse. We verified prognostic value of the found markers in a small group of patients with TKI discontinuation and demonstrated their high sensitivity (77%), specificity (86%), positive (85%), and negative (79%) predictive values. Thus we revealed genetic variants, which are potential markers of outcome prediction in CML patients after TKI discontinuation.

  9. 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

  10. Health Promotion for Adolescent Childhood Leukemia Survivors: Building on Prevention Science and eHealth

    OpenAIRE

    Elliot, Diane L.; Lindemulder, Susan J; Goldberg, Linn; Stadler, Diane D.; Smith, Jennifer

    2012-01-01

    Teenage survivors of childhood acute lymphoblastic leukemia (ALL) have increased morbidity likely due to their prior multicomponent treatment. Habits established in adolescence can impact individuals’ subsequent adult behaviors. Accordingly, healthy lifestyles, avoiding harmful actions, and appropriate disease surveillance are of heightened importance among teenage survivors. We review the findings from prevention science and their relevance to heath promotion. The capabilities and current us...

  11. Prevention of meningeal relapses in acute lymphoblastic leukemia; Zapobieganie wznowom oponowym w ostrej bialaczce limfoblastycznej

    Energy Technology Data Exchange (ETDEWEB)

    Armata, J. [Polsko-Amerykanski Instytut Pediatrii, Collegium Medicum, Uniwersytet Jagiellonski, Cracow (Poland)

    1993-12-31

    The paper describes modern methods of preventing meningeal leukemia which, in view of the noxiousness of skull radiotherapy, increasingly restrict the use of this method in a growing number of children.(author) 25 refs, 3 tabs

  12. 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

    Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; 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 Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  13. ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Xu, Heng; Cheng, Cheng; Devidas, Meenakshi; Pei, Deqing; Fan, Yiping; Yang, Wenjian; Neale, Geoff; Scheet, Paul; Burchard, Esteban G.; Torgerson, Dara G.; Eng, Celeste; Dean, Michael; Antillon, Frederico; Winick, Naomi J.; Martin, Paul L.; Willman, Cheryl L.; Camitta, Bruce M.; Reaman, Gregory H.; Carroll, William L.; Loh, Mignon; Evans, William E.; Pui, Ching-Hon; Hunger, Stephen P.; Relling, Mary V.; Yang, Jun J.

    2012-01-01

    Purpose Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10−20 in whites; P = 1 × 10−6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10−8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease. PMID:22291082

  14. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  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. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  17. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  18. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-01-07

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  19. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study.

    Science.gov (United States)

    Cartron, Guillaume; de Guibert, Sophie; Dilhuydy, Marie-Sarah; Morschhauser, Franck; Leblond, Veronique; Dupuis, Jehan; Mahe, Beatrice; Bouabdallah, Reda; Lei, Guiyuan; Wenger, Michael; Wassner-Fritsch, Elisabeth; Hallek, Michael

    2014-10-02

    GAUGUIN evaluated the safety and efficacy of obinutuzumab (GA101) monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In phase 1 (dose escalation), 13 patients received obinutuzumab 400 to 1200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2-8). In phase 2, 20 patients received a fixed dose of 1000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2-8). Infusion-related reactions occurred in nearly all patients, but few were grade 3/4. Grade 3/4 neutropenia occurred in 7 patients in phase 1 (but was not dose-related) and in 4 patients in phase 2. Overall end-of-treatment response (all partial responses) was 62% (phase 1) and 15% (phase 2); best overall response was 62% and 30%, respectively. Phase 2 median progression-free survival was 10.7 months and median duration of response was 8.9 months. In summary, obinutuzumab monotherapy is active in patients with heavily pretreated relapsed/refractory CLL.

  20. Outpatient-Based Therapy of Oral Fludarabine and Subcutaneous Alemtuzumab for Asian Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    William Y. K. Hwang

    2009-01-01

    Full Text Available Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL, but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA for the treatment of relapsed/refractory CLL. Results. Depending on their response, patients were given two to six 28-day cycles of subcutaneous alemtuzumab 30 mg on days 1,3, and 5 and oral fludarabine 40 mg/m2/day for 5 days. Median patient age was 74. The lymphocyte counts of all five patients fell after the 1st cycle of treatment and reached normal/low levels on completion of 2 to 6 cycles of therapy. Platelet counts and hemoglobin were unaffected. All five patients achieved complete hematological remission, while two attained minimal residual disease negativity on 4-color flow cytometry. Conclusions. Our OFSA regimen was effective in elderly Asian patients with relapsed/refractory CLL, and it should be investigated further.

  1. HLA-B67 may be a male-specific HLA marker of susceptibility to relapsed childhood ALL in Hong Kong Chinese and HLA-A33 or HLA-B17 signifies a higher presentation leukocytosis: A retrospective analysis on 53 transplant candidates (1989-2003).

    Science.gov (United States)

    Ng, Margaret H L; Lau, K M; Hawkins, B R; Chik, K W; Chan, Natalie P H; Wong, W S; Tsang, K S; Shing, Matthew M K; Li, C K

    2006-08-01

    We performed a retrospective analysis on the human leukocyte antigen (HLA) data of 53 consecutive Chinese patients with high-risk childhood acute lymphoblastic leukemia (ALL) diagnosed from 1989 to 2003. A significantly higher frequency of HLA-B67 in the male relapse group of patients [OR, 23.08; 95% CI, 5.31-100.36; p = 0.0042; for statistical significance after Bonferroni correction (Bc) p (Bc) B17 (p < 0.001) signifies higher leukocytosis at presentation. Taken together, our findings support the involvement of HLA in Chinese high-risk childhood ALL.

  2. Childhood leukemia and parents' occupational and home exposures.

    Science.gov (United States)

    Lowengart, R A; Peters, J M; Cicioni, C; Buckley, J; Bernstein, L; Preston-Martin, S; Rappaport, E

    1987-07-01

    A case-control study of children of ages 10 years and under in Los Angeles County was conducted to investigate the causes of leukemia. The mothers and fathers of acute leukemia cases and their individually matched controls were interviewed regarding specific occupational and home exposures as well as other potential risk factors associated with leukemia. Analysis of the information from the 123 matched pairs showed an increased risk of leukemia for children whose fathers had occupational exposure after the birth of the child to chlorinated solvents [odds ratio (OR) = 3.5, P = .01], spray paint (OR = 2.0, P = .02), dyes or pigments (OR = 4.5, P = .03), methyl ethyl ketone (CAS: 78-93-3; OR = 3.0, P = .05), and cutting oil (OR = 1.7, P = .05) or whose fathers were exposed during the mother's pregnancy with the child to spray paint (OR = 2.2, P = .03). For all of these, the risk associated with frequent use was greater than for infrequent use. There was an increased risk of leukemia for the child if the father worked in industries manufacturing transportation equipment (mostly aircraft) (OR = 2.5, P = .03) or machinery (OR = 3.0, P = .02). An increased risk was found for children whose parents used pesticides in the home (OR = 3.8, P = .004) or garden (OR = 6.5, P = .007) or who burned incense in the home (OR = 2.7, P = .007). The risk was greater for frequent use. Risk of leukemia was related to mothers' employment in personal service industries (OR = 2.7, P = .04) but not to specified occupational exposures. Risk related to fathers' exposure to chlorinated solvents, employment in the transportation equipment-manufacturing industry, and parents' exposure to household or garden pesticides and incense remains statistically significant after adjusting for the other significant findings.

  3. Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.

    Science.gov (United States)

    Police, Rachel L; Trask, Peter C; Wang, Jianmin; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Colosia, Ann; Njue, Annete; Sherrill, Beth; Ruiz-Soto, Rodrigo; Kaye, James A; Hamadani, Mehdi

    2015-04-01

    This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional well-designed RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.

  4. Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup.

    Science.gov (United States)

    Hospital, Marie-Anne; Prebet, Thomas; Bertoli, Sarah; Thomas, Xavier; Tavernier, Emmanuelle; Braun, Thorsten; Pautas, Cécile; Perrot, Aurore; Lioure, Bruno; Rousselot, Philippe; Tamburini, Jérôme; Cluzeau, Thomas; Konopacki, Johanna; Randriamalala, Edouard; Berthon, Céline; Gourin, Marie-Pierre; Recher, Christian; Cahn, Jean-Yves; Ifrah, Norbert; Dombret, Hervé; Boissel, Nicolas

    2014-08-21

    Although core-binding factor-acute myeloid leukemia (CBF-AML) (t[8;21] or inv[16]/t[16;16]) represents a favorable cytogenetic AML subgroup, 30% to 40% of these patients relapse after standard intensive chemotherapy. The encouraging results of gemtuzumab ozogamicin (GO) in newly diagnosed AML, and particularly in CBF-AML, incited us to retrospectively investigate the impact of GO-based salvage in these patients. We retrospectively analyzed the outcome of 145 patients with CBF-AML (59 t[8;21], 86 inv[16]/t[16;16]) in first relapse. As salvage, 48 patients received GO-based chemotherapy and 97 patients received conventional chemotherapy. Median age was 43 years (range, 16-76). Median first complete remission duration was 12.1 months (range, 2.1-93.6). Overall, second complete remission (CR2) rate was 88%. With a median follow-up from relapse of 3.5 years, the estimated 5-year disease-free survival (DFS) was 50% and 5-year overall survival (OS) was 51%. Older age and shorter first complete remission duration was associated with a shorter OS. Patients treated with GO had similar CR2 rate but significantly higher 5-year DFS (68% vs 42%; P = .05) and OS (65% vs 44%; P = .02). In multivariate analysis, GO salvage was still associated with a significant benefit in DFS and OS. In the 78 patients who received allogeneic hematopoietic stem cell transplantation in CR2, GO before transplant significantly improved posttransplant DFS and OS without excess of treatment-related mortality.

  5. 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

  6. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

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

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  7. Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Rotevatn, Elisabeth Orskov; Rosthøj, Susanne;

    2014-01-01

    therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol. PROCEDURE: We explored the pattern of SMN and relapse in the NOPHO...

  8. A 25-Year-Old Man with Exudative Retinal Detachments and Infiltrates without Hematological or Neurological Findings Found to Have Relapsed Precursor T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Jordan S. Johnson

    2015-09-01

    Full Text Available Background: Precursor T-cell acute lymphoblastic leukemia (pre-T-ALL may cause ocular pathologies such as cotton-wool spots, retinal hemorrhage, and less commonly, retinal detachment or leukemic infiltration of the retina itself. However, these findings are typically accompanied by the pathognomonic hematological signs of acute leukemia. CasePresentation: In this case report and review of the literature, we describe a particularly unusual case of a 25-year-old man who presented to our hospital with bilateral exudative retinal detachments associated with posterior pole thickening without any hematological or neurological findings. The patient, who had a history of previously treated pre-T-ALL in complete remission, was found to have leukemia cell infiltration on retinal biopsy. Conclusion: Our case underscores the fact that the ophthalmologist may be the first provider to detect the relapse of previously treated leukemia, and that ophthalmic evaluation is critical for detecting malignant ocular infiltrates.

  9. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Uzunel, Mehmet; Sairafi, Darius; Remberger, Mats; Mattsson, Jonas; Uhlin, Michael

    2014-07-15

    In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The δRec-ψJα signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (Pleukemia, high TREC levels were correlated with improved RFS (Pafter allogeneic hematopoietic stem cell transplantation.

  11. A HIGHER INCIDENCE OF RELAPSE FOR ACUTE LYMPHOCYTIC LEUKEMIA TREATED WITH ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CONDITIONED WITH BU-CY2 REGIMEN

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 钟隽; 张涛; 曾慧兰

    2003-01-01

    Objective: To analyze long-term outcome in sixty leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) following busulfan and cyclophosphamide (BU-CY2) between 1994 and 2000. Methods: BU-CY2 was used as the conditioning regimen and allo-HSCT was performed for all patients. All the patients were followed-up until August 2001 or death. The leukemia-free survival, relapse and transplant-related mortality were discussed. Results: All 60 patients had sustained engraftment. Acute GVHD occurred in 22 out of 60 patients (36.7%), and the incidence of acute GVHD was 48% in the patients with CML, 30% in AML and 26.7% in ALL. 38 patients are still alive in continuous remission with a median follow-up of 30 months (range 12-84) and 22 patients have died. The main causes of death were acute GVHD in 3 patients, CMV-IP in 7 patients and relapse in 11 patients, the remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 patients with ALL relapsed in the early stage post transplant (8/15, 53.3%), relapse was observed in the remaining 3 patients with AML, and however, no relapse was observed in CML. The probability of disease-free survival at 3 years for CML. AML and ALL patients was 80%, 70% and 26.7%, respectively. Conclusion: This results suggests that BU-CY2 is an effective conditioning regimen in patients with AML and CML, resulting in a low relapse rate and high long-term survival rate, but not as effective in patients with ALL, with a higher incidence of relapse and therefore, not recommended for ALL patients.

  12. Efficacy of lenalidomide in relapsed/refractory chronic lymphocytic leukemia patient: a systematic review and meta-analysis.

    Science.gov (United States)

    Liang, Liang; Zhao, Ming; Zhu, Yuan-Chao; Hu, Xin; Yang, Li-Ping; Liu, Hui

    2016-09-01

    Therapeutic results of relapsed/refractory chronic lymphocytic leukemia (CLL) are very disappointing at present. Lenalidomide has been proved to be effective for relapsed/refractory CLL as a single agent or in combination with various chemo-immunotherapeutic regimens. However, current clinical experience in its usage is still limited. Because of existing considerable variability in different studies, a systematic review and meta-analysis was conducted to describe overall response rate (ORR) of lenalidomide in patients with relapsed/refractory CLL. Pooled estimate of cumulative prevalence of total ORR was 42.23 % (95 % confidence interval [CI], 32.49-52.61 %), while pooled ORR in regimen with lenalidomide plus anti-CD20 monoclonal antibody (mAbs) and lenalidomide mono-therapy were 60.01 % (95 % CI, 53.86-65.86 %) and 24.38 % (95 % CI, 16.15-35.06 %), respectively. There was no significant difference between L + R (lenalidomide plus rituximab) group and L + O (lenalidomide plus ofatumumab) group, with pooled ORR of 66.38 % (95 % CI, 57.96-73.87 %) and 57.40 % (95 % CI, 46.46-67.65 %), respectively. When co-administrated with anti-CD20 mAbs, dosage of lenalidomide was not the key factor of ORR in combination therapy. Pooled ORR of patient with high-risk cytogenetic in L + anti-CD20 mAbs group was 56.74 % (95 % CI, 45.53-67.30 %). In comparison with patients without high-risk cytogenetic receiving the same treatment regimen, no significant difference was observed, with relative risk (RR) of 0.87 (95 % CI 0.68-1.11). Our finding demonstrated that lenalidomide plus anti-CD20 mAbs could be an efficient therapy regimen for relapsed/refractory CLL patients, especially for those with high-risk cytogenetic factor.

  13. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-09

    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 With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  14. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  15. 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...

  16. 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...

  17. Combination of bendamustine and rituximab in the management of relapsed and refractory chronic lymphocytic leukemia: the results of retrospective study

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2015-01-01

    Full Text Available Efficacy and safety results of rituximab and bendamustine combination (Scheme BR in patients with relapsed and refractory chronic lymphocytic leukemia (CLL are presented. From 01.2012 to 04.2013, the treatment was initiated in 43 patients (21 with relapses are sensitive to the last line of therapy; 22 – with refractory CLL. Median age at start of therapy was 63.5 years (range from 43 to 81 years. In 40 patients response was evaluated according to NCI-WG criteria (1996. Complete remission (CR is documented in 5 (12.5 % cases, partial (PR or nodular partial remission (nPR in 17 (42.5 % cases. MRD-negative CR was achieved in 1 (20.0 % of 5 patients with CR. With 23.5 months of median follow-up for surviving patients 2-year progression-free survival (PFS was 47.2 ± 8.5 % (median – 18.5 months, overall survival (OS – 66.9 ± 7.9 % (median not achieved. Hematological toxicity Grade 3–4 occurred in 15 (34.9 % cases, same degree infectious complicationsin 5 (11.6 % cases. Patients received 3 or more therapy lines before this treatment (37.5 ± 16.1 % against 74.7 ± 8.3 %; p = 0.016, with «bulky disease» more than 10 cm (0.0 % vs. 75.4 ± 7.5 %; p < 0.001 and received rituximab in combination with chemotherapy in the previous lines, compared to the «naive» cases (44.1 ± 10.5 % against 92.9 ± 6.9 %; p = 0.009 have significantly worsened 2-year OS.

  18. Temporal changes in water quality at a childhood leukemia cluster

    Science.gov (United States)

    Seiler, R.L.

    2004-01-01

    Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter

  19. 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

  20. Over-expression of heme oxygenase-1 in peripheral blood predicts the progression and relapse risk of chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    Wei Sixi; Wang Yating; Chai Qixiang; Fang Qin; Zhang Yaming; Lu Yinghao; Wang Jishi

    2014-01-01

    Background There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML).Heme oxygenase-1 (HO-1),as one of the most important oxidation-regulating enzymes in vivo,suggests the onset and progression of cancer when highly expressed.Furthermore,HO-1 level is related with the occurrence and development of hematological diseases.But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto.This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.Methods A total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR.Routine blood test was performed to detect the changes of leukocyte and platelet counts.The proportion of primitive cells in BM was detected by flow cytometry.The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis.The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.Results Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P <0.0001),which were 0.57±3.78 and (1.417±1.125)×10-6,respectively.HO-1 expression level in CML patients was 0.061 5±0.062 4,which decreased to 0.009 4±0.006 7 upon CMoR,and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)× 10-6,P <0.001.When relapse occurred,HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse.According to progression of CML,HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7± 0.447 0).And there was a linear correlation between HO-1 expression

  1. Population-based case-control study of childhood leukemia in Shanghai

    Energy Technology Data Exchange (ETDEWEB)

    Shu, X.O.; Gao, Y.T.; Brinton, L.A.; Linet, M.S.; Tu, J.T.; Zheng, W.; Fraumeni, J.F. Jr.

    1988-08-01

    A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio (OR) = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.

  2. Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic trioxide-based therapy in relapsed acute promyelocytic leukemia patients.

    Science.gov (United States)

    Lou, Yinjun; Ma, Yafang; Sun, Jianai; Ye, Xiujin; Pan, Hanzhang; Wang, Yungui; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; He, JingSong; Tong, Hongyan; Jin, Jie

    2015-11-01

    The aim of the study is to better understand the mechanism of relapse and acquired clinical resistance to arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Thirty relapsed acute promyelocytic leukemia (APL) patients were followed. Fifteen patients experienced two or more relapses; nine patients had clinical resistance to ATO-based therapy. The frequency and clinical significance of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) mutational status using Sanger sequencing were evaluated. Overall, eight different types of mutations in the RARA region (V218D, R272Q, T278A, T291I, N299D, R294W, A300G, and L220_F228delinsP) were identified in 11 patients. Eight missense mutations (L211P, C213R, S214L, A216V, L217F, D219H, S221G, and D241G) were found in the PML portion of PML-RARA in 14 patients, with A216V as the predominant mutation. Eight patients were found to harbor both PML and RARA mutations over the course of the disease. The PML-region mutations were associated with response to ATO-based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P = 0.013). Notably, one case sampled at nine different time points showed alternating clonal dominance over the course of treatment. This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance.

  3. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-24

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  4. Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  5. Incidence of childhood leukemia and oil exploitation in the Amazon basin of Ecuador.

    Science.gov (United States)

    Hurtig, Anna-Karin; San Sebastián, Miguel

    2004-01-01

    To determine whether there was any difference in childhood leukemia incidence rates between populations living in the proximity to oil fields and those living in areas free from oil exploitation in the Amazon basin of Ecuador, 91 cancer cases among children (0-14 years) from the provinces of Sucumbios, Orellana, Napo, and Pastaza during the period 1985-2000 were studied. The relative risks for all leukemias indicated significantly elevated levels in the youngest age group (0-4 years), both genders combined (RR 3.48, 95% CI 1.25-9.67), and in all age groups (0-14 years) combined for females (RR 2.60, 95% CI 1.11-6.08) and both genders combined (RR 2.56, 95% CI 1.35-4.86). There was no significant difference between the two groups in all other cancer sites combined. Study results are compatible with a relationship between childhood leukemia incidence and living in the proximity of oil fields in the Ecuadorian Amazon.

  6. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    Science.gov (United States)

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches

  7. Differences in Childhood Leukemia Incidence and Survival between Southern Thailand and the United States: A Population-Based Analysis

    Science.gov (United States)

    Demanelis, Kathryn; Sriplung, Hutcha; Meza, Rafael; Wiangnon, Surapon; Rozek, Laura S.; Scheurer, Michael E.; Lupo, Philip J.

    2015-01-01

    BACKGROUND Childhood leukemia incidence and survival varies globally, and this variation may be attributed to environmental risk factors, genetics, and/or disparities in diagnosis and treatment. PROCEDURE We analyzed childhood leukemia incidence and survival trends in children age 0–19 years from 1990 to 2011 in Songkhla, Thailand (n=316) and compared these results to US data from the Surveillance, Epidemiology, and End Results (SEER) registry (n=6,738). We computed relative survival using Ederer II and estimated survival functions using the Kaplan-Meier method. Changes in incidence and five-year survival by year of diagnosis were evaluated using joinpoint regression and are reported as annual percent changes (APC). RESULTS The age-standardized incidence of leukemia was 3.2 and 4.1 cases per 100,000 in Songkhla and SEER-9, respectively. In Songkhla, incidence from 1990–2011 significantly increased for leukemia (APC=1.7%, p=0.031) and acute lymphoblastic leukemia (ALL) (APC=1.8%, p=0.033). Acute myeloid leukemia (AML) incidence significantly increased (APC=4.2%, p=0.044) and was significantly different from the US (p=0.026), where incidence was stable during the same period (APC=0.3%, p=0.541). The overall five-year relative survival for leukemia was lower than that reported in the US (43% vs. 79%). Five-year survival significantly improved by at least 2% per year from 1990–2011 in Songkhla for leukemia, ALL, and AML (p<0.050). CONCLUSIONS While leukemia and ALL incidence increased in Songkhla, differences in leukemia trends, particularly AML incidence, may suggest etiologic or diagnostic differences between Songkhla and the US. This work highlights the importance of evaluating childhood cancer trends in low- and middle-income countries. PMID:25962869

  8. 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.

  9. Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    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.

  10. Maintenance therapy of childhood acute lymphoblastic leukemia revisited

    DEFF Research Database (Denmark)

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

    2016-01-01

    adjustment guidelines. PROCEDURE: To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP...... maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10(9) /l. RESULTS: After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery.......00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10(9) /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, rs = 0.77; P

  11. Application of FTIR microspectroscopy for the follow-up of childhood leukemia chemotherapy

    Science.gov (United States)

    Mordechai, Shaul; Mordehai, J.; Ramesh, Jagannathan; Levi, C.; Huleihal, Mahmud; Erukhimovitch, Vitaly; Moser, A.; Kapelushnik, J.

    2001-11-01

    Acute Lymphoblastic Leukemia (ALL) accounts for majority of the childhood leukemia. Outcome of children with ALL treatment has improved dramatically. Sensitive techniques are available today for detection of minimal residual disease in children with ALL, which provide insight into the effective cytotoxic treatment. Here, we present a case study, where lymphocytes isolated from two children before and after the treatment were characterized using microscopic Fourier Transform Infrared spectroscopy. Significant changes in the absorbance and spectral pattern in the wavenumber region between 800-1800 cm-1 were found after the treatment. Preliminary analysis of the spectra revealed that the protein content decreased in the T-lymphoma patient before the treatment in comparison to the age matched controls. The chemotherapy treatment resulted in decreased nucleic acids, total carbohydrates and cholesterol contents to a remarkable extent in both B and T lymphoma patients.

  12. Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

    DEFF Research Database (Denmark)

    Bräuner, E.V.; Andersen, Claus Erik; Andersen, H.P.;

    2010-01-01

    Background: In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. Hypothesis: Traffic exhaust in the air enhances the risk association between radon...... risk within different strata of air pollution and traffic density. Results: The relative risk for childhood leukemia in association with a 103 Bq/m3-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NOx and 1.23 (0.79, 1.91) for those exposed to low levels of NOx...... pollution from traffic may enhance the effect of radon on the risk of childhood leukemia. The observed tendency may also be attributed to chance. © 2010 Springer Science+Business Media B.V....

  13. Unconventional oil and gas development and risk of childhood leukemia: Assessing the evidence.

    Science.gov (United States)

    Elliott, Elise G; Trinh, Pauline; Ma, Xiaomei; Leaderer, Brian P; Ward, Mary H; Deziel, Nicole C

    2017-01-15

    The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into

  14. GSTM1 and GSTT1 null polymorphisms and childhood acute leukemia risk: evidence from 26 case-control studies.

    Directory of Open Access Journals (Sweden)

    Qiuqin Tang

    Full Text Available Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase mu-1 (GSTM1 and glutathione S-transferase theta-1 (GSTT1 null polymorphisms and childhood acute leukemia; however, the conclusions remain controversial. We performed an extensive meta-analysis on 26 published case-control studies with a total of 3252 cases and 5024 controls. Crude odds ratios (ORs with 95% confidence interval were used to assess the strength of association between childhood acute leukemia risk and polymorphisms of GSTM1 and GSTT1. With respect to GSTM1 polymorphism, significantly increased risk of childhood acute leukemia was observed in the overall analysis (OR = 1.30; 95%CI, 1.11-1.51. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism are associated with childhood acute leukemia in group of Asians (OR = 1.94; 95%CI, 1.53-2.46, Blacks (OR = 1.76; 95%CI, 1.07-2.91, ALL (OR = 1.33; 95%CI, 1.13-1.58, '< 100 cases and <100 controls' (OR = 1.79; 95%CI, 1.21-2.64, '≥ 100 cases and ≥ 100 controls' (OR = 1.25; 95%CI, 1.02-1.52, and population-based control source (OR = 1.40; 95%CI, 1.15-1.69. With respect to GSTT1 polymorphism, significant association with childhood acute leukemia risk was only found in subgroup of Asian. This meta-analysis supports that GSTM1 null polymorphism is capable of causing childhood acute leukemia susceptibility.

  15. Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Andersen, Claus Erik; Andersen, Helle P.;

    2010-01-01

    for different morphological subtypes of leukemia and within different strata of traffic density showed a non-significant pattern of stronger associations between radon and childhood leukemia within strata of higher traffic density at the street address. Air pollution from traffic may enhance the effect of radon...... of air pollution and traffic density. The relative risk for childhood leukemia in association with a 10(3) Bq/m(3)-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NOx and 1.23 (0.79, 1.91) for those exposed to low levels of NOx (p (interaction,) 0.17). Analyses......In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. Traffic exhaust in the air enhances the risk association between radon and childhood leukemia. We...

  16. Extremely Low Frequency Electromagnetic Field (ELF-EMF and childhood leukemia near transmission lines: a review

    Directory of Open Access Journals (Sweden)

    P. A. Kokate

    2016-04-01

    Full Text Available This article presents a systematic review of most cited studies from developed countries those shed light on the potential relation between childhood leukemia and extremely low frequency electromagnetic field (ELF-EMF. All the findings of articles critically segregated as per some neglected parameters like number of samples, exposure duration, frequency range, distance from the radiation sources, and location during measurement of magnetic field density near power lines. Literature of major 50 studies are divided according to pooled analysis / meta-analysis, residential zone assessment and case-control studies.

  17. 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

    of acceptable toxicity, an individualized therapeutic approach is indicated. The mapping of the human genome and technological developments in DNA sequencing, gene expression profiling, and proteomics have raised the expectations for implementing genotype-phenotype data into the clinical decision process...... 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...

  18. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    Science.gov (United States)

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.

  19. Association of Attention Deficit Disorder With Bedside Anti-saccades in Survivors of Childhood Leukemia.

    Science.gov (United States)

    Khan, Raja B; Hudson, Melissa M; Ness, Kirsten K; Liang, Zhu; Srivastava, Deokumar; Krull, Kevin R

    2016-02-01

    Impaired attention is well recognized in childhood cancer survivors. We prospectively evaluated 162 long-term survivors of childhood acute lymphoblastic leukemia to study an association between presence of neurologic soft signs as measured by Zurich Neuromotor Scale, bedside evaluation of anti-saccades, and attention deficit disorder. Attention deficit disorder was recognized in 10.5% of the study cohort. We did not find an association of attention deficit with presence of any soft sign. However, there was an association between presence of abnormal anti-saccades and attention deficit (P = .04). These results will require further validation and if confirmed may introduce a quick bedside method of assessing impaired attention in cancer survivors.

  20. 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.

  1. TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    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

  2. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  3. Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes.

    Science.gov (United States)

    Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, M Fatih; Scheurer, Michael E; Baum, Marianna K; Dorak, M Tevfik

    2014-09-01

    Hereditary hemochromatosis (HFE) variants correlating with body iron levels have shown associations with cancer risk, including childhood acute lymphoblastic leukemia (ALL). Using a multi-ethnic sample of cases and controls from Houston, TX, we examined two HFE variants (rs1800562 and rs1799945), one transferrin receptor gene (TFRC) variant (rs3817672) and three additional iron regulatory gene (IRG) variants (SLC11A2 rs422982; TMPRSS6 rs855791 and rs733655) for their associations with childhood ALL. Being positive for either of the HFE variants yielded a modestly elevated odds ratio (OR) for childhood ALL risk in males (1.40, 95% CI=0.83-2.35), which increased to 2.96 (95% CI=1.29-6.80) in the presence of a particular TFRC genotype for rs3817672 (P interaction=0.04). The TFRC genotype also showed an ethnicity-specific association, with increased risk observed in non-Hispanic Whites (OR=2.54, 95% CI=1.05-6.12; P interaction with ethnicity=0.02). The three additional IRG SNPs all showed individual risk associations with childhood ALL in males (OR=1.52-2.60). A polygenic model based on the number of variant alleles in five IRG SNPs revealed a linear increase in risk among males with the increasing number of variants possessed (OR=2.0 per incremental change, 95% CI=1.29-3.12; P=0.002). Our results replicated previous HFE risk associations with childhood ALL in a US population and demonstrated novel associations for IRG SNPs, thereby strengthening the hypothesis that iron excess mediated by genetic variants contributes to childhood ALL risk.

  4. Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia.

    Science.gov (United States)

    Griffith, Malachi; Griffith, Obi L; Krysiak, Kilannin; Skidmore, Zachary L; Christopher, Matthew J; Klco, Jeffery M; Ramu, Avinash; Lamprecht, Tamara L; Wagner, Alex H; Campbell, Katie M; Lesurf, Robert; Hundal, Jasreet; Zhang, Jin; Spies, Nicholas C; Ainscough, Benjamin J; Larson, David E; Heath, Sharon E; Fronick, Catrina; O'Laughlin, Shelly; Fulton, Robert S; Magrini, Vincent; McGrath, Sean; Smith, Scott M; Miller, Christopher A; Maher, Christopher A; Payton, Jacqueline E; Walker, Jason R; Eldred, James M; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; Westervelt, Peter; Kulkarni, Shashikant; DiPersio, John F; Mardis, Elaine R; Wilson, Richard K; Ley, Timothy J

    2016-07-01

    The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome.

  5. Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHONG Zhao-dong; LUO Yi; ZOU Ping; ZHENG Jin-e; YAO Jun-xia; HUANG Shi-ang; ZHOU Dong-feng; YOU Yong

    2012-01-01

    A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA).Three re-induction chemotherapies were administered,and partial remission was achieved.The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation.The patient achieved complete cytogenetical remission.This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

  6. Minimal Residual Disease and Childhood Leukemia: Standard of Care Recommendations From the Pediatric Oncology Group of Ontario MRD Working Group.

    Science.gov (United States)

    Athale, Uma H; Gibson, Paul J; Bradley, Nicole M; Malkin, David M; Hitzler, Johann

    2016-06-01

    Minimal residual disease (MRD) is an independent predictor of relapse risk in children with leukemia and is widely used for risk-adapted treatment. This article summarizes current evidence supporting the use of MRD, including clinical significance, current international clinical practice, impact statement, and recommended indications. The proposed MRD recommendations have been endorsed by the MRD Working Group of the Pediatric Oncology Group of Ontario and provide the foundation for a strategy that aims at equitable access to MRD evaluation for children with leukemia.

  7. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-02-07

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

  8. Leukemia

    Science.gov (United States)

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

  9. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  10. 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 and to...

  11. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML.

    NARCIS (Netherlands)

    Hollink, I.H.; Zwaan, C.M.; Zimmermann, M.; Arentsen-Peters, T.C.; Pieters, R.; Cloos, J.; Kaspers, G.J.L.; Graaf, S.S.N. de; Harbott, J.; Creutzig, U.; Reinhardt, D.; Heuvel-Eibrink, M.M. van den; Thiede, C.

    2009-01-01

    Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mu

  12. 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

  13. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    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.

  14. The frequency of NPM1 mutations in childhood acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Karamolegou Kalliopi

    2010-10-01

    Full Text Available Abstract Background Mutations in the nucleophosmin (NPM1 gene have been solely associated with childhood acute myeloid leukemia (AML. We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations. Results NPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290 and (S293 in the NPM protein. FLT3/ITD mutations were observed in 12% of the cases and in one NPM1-mutated case bearing also t(8;21 (q22;q22. No common RAS mutations were identified. Conclusions A relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.

  15. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study.

    Science.gov (United States)

    Gorin, Norbert-Claude; Isnard, Françoise; Garderet, Laurent; Ikhlef, Souhila; Corm, Selim; Quesnel, Bruno; Legrand, Ollivier; Cachanado, Marine; Rousseau, Alexandra; Laporte, Jean-Philippe

    2013-10-01

    The outlook for adults with refractory and relapsed acute lymphocytic leukemia (ALL) is poor. CD52 is expressed in most patients with ALL. Alemtuzumab is an anti-CD52 humanized monoclonal antibody. This phase II study assessed the efficacy of alemtuzumab combined with granulocyte-colony stimulating factor (G-CSF) to boost antibody-dependent cell cytotoxicity mediated by neutrophils. Twelve patients with relapsed (n = 11) or refractory (n = 1) ALL, including four relapses postallogeneic stem cell transplantation, were treated and monitored between October 2006 and January 2011. Patients received 1 wk of alemtuzumab every other day at increasing doses of 3, 10, and 30 mg to test tolerance and 30 mg three times a week for 12-18 infusions. If in complete remission (CR), patients received maintenance therapy for 1 wk, every 2 months. G-CSF was administered at 5 μg/kg per day during alemtuzumab administration. The primary endpoint was disappearance of blast cells on a marrow aspirate. CD52 was expressed in all patients. Four patients reached CR. In one additional patient, clearance of blast cells was observed in peripheral blood but not in the marrow. The most frequent adverse events during course 1 of treatment were fever and chills (n = 3), skin rash (n = 3), and bronchospasm (n = 2). Tumor lysis syndrome was observed at treatment initiation in one patient who reached CR. All patients progressed within a few months and all but one died. The surviving patient is still alive after relapse and a second allogeneic stem cell transplantation. This study shows that in relapse/refractory ALL, alemtuzumab with G-CSF can produce good responses of short duration.

  16. Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

    Science.gov (United States)

    Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni Th; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E; Mueller, Beth A; Mora, Ana M; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M; Francis, Stephen S; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G

    2017-01-01

    Summary Background Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1.06 (95% CI 0.99–1.13), and was significant for prelabour caesarean delivery and ALL (1.23 [1.04-1.47]; p=0.018). Emergency caesarean delivery was not associated with ALL (OR 1.02 [95% CI 0.81-1.30]). AML was not associated with caesarean delivery (all indications OR 0.99 [95% CI 0.84-1.17]; prelabour caesarean delivery 0.83 [0.54-1.26]; and emergency caesarean delivery 1.05 [0.63-1.77]). Interpretation Our

  17. Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia-The GEOCAP Study, 2002-2007.

    Science.gov (United States)

    Houot, Jennifer; Marquant, Fabienne; Goujon, Stéphanie; Faure, Laure; Honoré, Cécile; Roth, Marie-Hélène; Hémon, Denis; Clavel, Jacqueline

    2015-10-15

    Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Géolocalisation des Cancers Pédiatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Île-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95% confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Île-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy-traffic road density near a child's home. The results support a role for traffic-related benzene exposure in the etiology of childhood AML.

  18. Phase I Study of Valspodar (PSC-833) with Mitoxantrone and Etoposide in Refractory and Relapsed Pediatric Acute Leukemia: A Report from the Children’s Oncology Group

    Science.gov (United States)

    O’Brien, Maureen M.; Lacayo, Norman J.; Lum, Bert L.; Kshirsagar, Smita; Buck, Steven; Ravindranath, Yaddanapudi; Bernstein, Mark; Weinstein, Howard; Chang, Myron N.; Arceci, Robert J.; Sikic, Branimir I.; Dahl, Gary V.

    2009-01-01

    Background Valspodar, a non-immunosuppressive analog of cylosporine, is a potent P-glycoprotein (MDR1) inhibitor. As MDR1-mediated efflux of chemotherapeutic agents from leukemic blasts may contribute to drug resistance, a phase 1 study of valspodar combined with mitoxantrone and etoposide in pediatric patients with relapsed or refractory leukemias was performed. Procedure Patients received a valspodar loading dose (2 mg/kg) followed by a five-day continuous valspodar infusion (8, 10, 12.5 or 15 mg/kg/day) combined with lower than standard doses of mitoxantrone and etoposide. The valspodar dose was escalated using a standard 3 + 3 phase I design. Results 21 patients were evaluable for toxicity and 20 for response. The maximum tolerated dose (MTD) of valspodar was 12.5 mg/kg/day, combined with 50% dose-reduced mitoxantrone and etoposide. The clearance of mitoxantrone and etoposide was decreased by 64% and 60%, respectively, when combined with valspodar. Dose-limiting toxicities included stomatitis, ataxia, and bone marrow aplasia. Three of 11 patients with acute lymphoblastic leukemia (ALL) had complete responses while no patient with acute myeloid leukemia (AML) had an objective response. In vitro studies demonstrated P-glycoprotein expression on the blasts of five of 14 patients, although only one had inhibition of rhodamine efflux by valspodar. Conclusions While this regimen was tolerable, responses in this heavily pretreated population were limited to a subset of patients with ALL. PMID:20209646

  19. Health promotion for adolescent childhood leukemia survivors: building on prevention science and ehealth.

    Science.gov (United States)

    Elliot, Diane L; Lindemulder, Susan J; Goldberg, Linn; Stadler, Diane D; Smith, Jennifer

    2013-06-01

    Teenage survivors of childhood acute lymphoblastic leukemia (ALL) have increased morbidity likely due to their prior multicomponent treatment. Habits established in adolescence can impact individuals' subsequent adult behaviors. Accordingly, healthy lifestyles, avoiding harmful actions, and appropriate disease surveillance are of heightened importance among teenage survivors. We review the findings from prevention science and their relevance to heath promotion. The capabilities and current uses of eHealth components including e-learning, serious video games, exergaming, behavior tracking, individual messaging, and social networking are briefly presented. The health promotion needs of adolescent survivors are aligned with those eHealth aspects to propose a new paradigm to enhance the wellbeing of adolescent ALL survivors.

  20. 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.

  1. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Science.gov (United States)

    Reisi, Nahid; Azhir, Afshin; Hashemipour, Mahin; Raeissi, Pouran; Amini, Abasgholi; Moafi, Alireza

    2009-01-01

    BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran. METHODS: During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR). RESULTS: The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003). CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors. PMID:21772869

  2. Quantitative morphologic evaluation of magnetic resonance imaging during and after treatment of childhood leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Reddick, Wilburn E.; Glass, John O. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research (MS 210), Department of Radiological Sciences, Memphis, TN (United States); Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States)

    2007-11-15

    Medical advances over the last several decades, including CNS prophylaxis, have greatly increased survival in children with leukemia. As survival rates have increased, clinicians and scientists have been afforded the opportunity to further develop treatments to improve the quality of life of survivors by minimizing the long-term adverse effects. When evaluating the effect of antileukemia therapy on the developing brain, magnetic resonance (MR) imaging has been the preferred modality because it quantifies morphologic changes objectively and noninvasively. Computer-aided detection of changes on neuroimages enables us to objectively differentiate leukoencephalopathy from normal maturation of the developing brain. Quantitative tissue segmentation algorithms and relaxometry measures have been used to determine the prevalence, extent, and intensity of white matter changes that occur during therapy. More recently, diffusion tensor imaging has been used to quantify microstructural changes in the integrity of the white matter fiber tracts. MR perfusion imaging can be used to noninvasively monitor vascular changes during therapy. Changes in quantitative MR measures have been associated, to some degree, with changes in neurocognitive function during and after treatment. In this review, we present recent advances in quantitative evaluation of MR imaging and discuss how these methods hold the promise to further elucidate the pathophysiologic effects of treatment for childhood leukemia. (orig.)

  3. Exposure to magnetic fields and survival after diagnosis of childhood leukemia: a German cohort study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Weihkopf, Thomas; Kaatsch, Peter

    2007-01-01

    Inspired by a recent U.S. study showing poorer survival among children with acute lymphoblastic leukemia (ALL) exposed to magnetic fields above 0.3 microT, we examine this relationship in a German cohort of childhood leukemia cases derived from previous population-based case-control studies...... conducted between 1992 and 2001. A total of 595 ALL cases with 24-h magnetic field measurements are included in the analysis with a median follow-up of 9.5 years. We calculate the hazard ratios (HR) using the Cox proportional hazards model for overall survival, adjusted for age at diagnosis, calendar year...... of diagnosis, and gender. Elevated hazards are found for exposures between 0.1 and 0.2 microT [HR, 2.6; 95% confidence interval (95% CI), 1.3-5.2], based on 34 cases with 9 deaths as well as for exposures above 0.2 microT (HR, 1.6; 95% CI, 0.6-4.4), based on 18 cases with 4 deaths. After adjustment...

  4. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse | Office of Cancer Genomics

    Science.gov (United States)

    The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.

  5. 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.

  6. Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Reyes-León, Adriana; Juárez-Velázquez, Rocío; Medrano-Hernández, Alma; Cuenca-Roldán, Teresa; Salas-Labadía, Consuelo; del Pilar Navarrete-Meneses, María; Rivera-Luna, Roberto; López-Hernández, Gerardo; Paredes-Aguilera, Rogelio; Pérez-Vera, Patricia

    2015-01-01

    Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms’s sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432), event free survival (p = 0.667) or overall survival (p = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification. PMID:26131904

  7. Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Adriana Reyes-León

    Full Text Available Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms's sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432, event free survival (p = 0.667 or overall survival (p = 0.531, inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7. In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification.

  8. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

  9. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

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    Nahid Reisi

    2009-04-01

    Full Text Available

    • BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
    • METHODS: During a 4-year period (2003 to 2007, 55 children (33 male and 22 female diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this crosssectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III criteria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR.
    • RESULTS: The mean age of participates was 10.4 years (range 6-19 years and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55 of survivors (10 male, 1 female met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004. Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was  ositively correlated with serum triglycerides (0.543, p < 0.001, systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively, insulin levels (0.914, p < 0.001 and blood sugar (0.398, p = 003.
    • CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
    • KEYWORDS: Acute lymphoblastic leukemia, metabolic syndrome, obesity, children.

  10. Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.

    Science.gov (United States)

    Wakita, S; Yamaguchi, H; Omori, I; Terada, K; Ueda, T; Manabe, E; Kurosawa, S; Iida, S; Ibaraki, T; Sato, Y; Todoroki, T; Hirakawa, T; Ryotokuji, T; Arai, K; Kitano, T; Mitamura, Y; Kosaka, F; Dan, K; Inokuchi, K

    2013-04-01

    Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at diagnosis and relapse of 34 adult AML patients. Five acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics-modifying gene mutations (Pgene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.

  11. Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

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    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.

  12. Phase I Pharmacokinetic and Pharmacodynamic Study of the Multikinase Inhibitor Sorafenib in Combination With Clofarabine and Cytarabine in Pediatric Relapsed/Refractory Leukemia

    Science.gov (United States)

    Inaba, Hiroto; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Li, Lie; Furmanski, Brian D.; Mascara, Gerard P.; Heym, Kenneth M.; Christensen, Robbin; Onciu, Mihaela; Shurtleff, Sheila A.; Pounds, Stanley B.; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Baker, Sharyn D.

    2011-01-01

    Purpose To assess the toxicity, pharmacokinetics, and pharmacodynamics of multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in children with relapsed/refractory leukemia. Patients and Methods Twelve patients with acute leukemia (11 with acute myeloid leukemia [AML]) received sorafenib on days 1 to 7 and then concurrently with cytarabine (1 g/m2) and clofarabine (stratum one: 40 mg/m2, n = 10; stratum two [recent transplantation or fungal infection]: 20 mg/m2, n = 2) on days 8 to 12. Sorafenib was continued until day 28 if tolerated. Two sorafenib dose levels (200 mg/m2 and 150 mg/m2 twice daily) were planned. Sorafenib pharmacokinetic and pharmacodynamic studies were performed on days 7 and 8. Results At sorafenib 200 mg/m2, two of four patients in stratum one and one of two patients in stratum two had grade 3 hand-foot skin reaction and/or rash as dose-limiting toxicities (DLTs). No DLTs were observed in six patients in stratum one at sorafenib 150 mg/m2. Sorafenib inhibited the phosphorylation of AKT, S6 ribosomal protein, and 4E-BP1 in leukemia cells. The rate of sorafenib conversion to its metabolite sorafenib N-oxide was high (mean, 33%; range, 17% to 69%). In vitro, the N-oxide potently inhibited FLT3–internal tandem duplication (ITD; binding constant, 70 nmol/L) and the viability of five AML cell lines. On day 8, sorafenib decreased blast percentages in 10 of 12 patients (median, 66%; range, 9% to 95%). After combination chemotherapy, six patients (three FLT3-ITD and three FLT3 wild-type AML) achieved complete remission, two (both FLT3-ITD AML) had complete remission with incomplete blood count recovery, and one (FLT3 wild-type AML) had partial remission. Conclusion Sorafenib in combination with clofarabine and cytarabine is tolerable and shows activity in relapsed/refractory pediatric AML. PMID:21768474

  13. Effective re-induction therapy with dasatinib and clofarabine in relapsed Philadelphia chromosome positive acute lymphoblastic leukemia

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    Anne Loes van den Boom

    2012-12-01

    Full Text Available This case discusses a 10 year old female patient with a late relapse of Ph-chromosome positive B-cell precursor acute lymphoblastic leukaemias (ALL who had previously been treated with chemotherapy and allogeneic stem-cell transplantation. Treatment for relapse consisted of single-agent dasatinib, followed by 2 blocks of a combination of dasatinib and clofarabine as consolidation therapy. Using this schedule both morphological and cytogenetic complete remission were obtained. This regimen was well tolerated, and no major toxicity concerns occurred. Subsequently, the patient received a 2nd stem cell transplantation from a matched unrelated donor. Unfortunately, the child died after complete molecular remission at day +104 post-transplantation, due to a disseminated adenoviral infection. We conclude that dasatinib and clofarabine combination therapy was safe and effective in this patient, and should be further explored as a salvage regimen in relapsed/refractory Philadelphia chromosome positive ALL patients.

  14. 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...... and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P

  15. 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...

  16. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model

    Institute of Scientific and Technical Information of China (English)

    Petar Ivanovski; Ivan Ivanovski; Dimitrije Nikoli(c); Ivana Jovanovi(c)

    2012-01-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations.The bottleneck is evidence that leukemia initiation,by in utero acquired chromosome translocations that generate functional fusion genes,is far more common than the incidence rate of corresponding leukemia.For childhood TEL-AML1+ acute lymphoblastic leukemia (ALL) this equates to approximately 100 times.Practically this means that among a hundred children born with TEL-AML1 fusion gene,only one child will later in its life develop ALL.The key data necessary for unraveling of this mystery were discovered in 2002.It was the level of TEL-AML1 + cells' frequency.The bottleneck is caused by the very low body TEL-AML1 + cell count.Only one out of a thousand B cells carries TEL-AML1 fusion gene.TEL-AML1+ body cell count is low because TEL-AML1 fusion is generated at cell level of 10a to 10-4 just during the late fetal lymphopoiesis i.e.after the 36th gestational week.

  17. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model.

    Science.gov (United States)

    Ivanovski, Petar; Ivanovski, Ivan; Nikolić, Dimitrije; Jovanović, Ivana

    2012-03-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells’ frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

  18. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.

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

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon;

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance th...... significance. These results indicate that oral MTX/6MP maintenance therapy administered after the first year of remission can improve the cure rates of children with T-lineage or with higher risk B-lineage ALL.......The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy with a multidrug cyclic LSA2L2 regimen. 135 children with B-lineage ALL and a white blood count > or =50 x 10/L and 98 children with T-lineage ALL were included. Of the 234 patients, the 135 patients who received MTX/6MP maintenance therapy had a lower relapse risk than the 98 patients who...

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

    Science.gov (United States)

    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

  1. Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Rohit Gulati

    2015-01-01

    Full Text Available Blast phase in chronic myelogenous leukemia (CML has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia, and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117. Fluorescence in situ hybridization (FISH of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

  2. Physical activity and late effects in childhood acute lymphoblastic leukemia long-term survivors.

    Science.gov (United States)

    Bertorello, N; Manicone, R; Galletto, C; Barisone, E; Fagioli, F

    2011-08-01

    In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.

  3. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Daver, N; Kantarjian, H; Ravandi, F; Estey, E; Wang, X; Garcia-Manero, G; Jabbour, E; Konopleva, M; O'Brien, S; Verstovsek, S; Kadia, T; Dinardo, C; Pierce, S; Huang, X; Pemmaraju, N; Diaz-Pines-Mateo, M; Cortes, J; Borthakur, G

    2016-02-01

    Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.

  4. A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

    Science.gov (United States)

    Yee, Karen W L; Chen, Hsiao-Wei T; Hedley, David W; Chow, Sue; Brandwein, Joseph; Schuh, Andre C; Schimmer, Aaron D; Gupta, Vikas; Sanfelice, Deborah; Johnson, Tara; Le, Lisa W; Arnott, Jamie; Bray, Mark R; Sidor, Carolyn; Minden, Mark D

    2016-10-01

    ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily.

  5. Exposure to electromagnetic fields (non-ionizing radiation) and its relationship with childhood leukemia: A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Calvente, I.; Fernandez, M.F. [Laboratory of Medical Investigations, San Cecilio University Hospital, CIBER de Epidemiologia y Salud Publica (CIBERESP) (Spain); Department of Radiology, University of Granada, Granada (Spain); Villalba, J. [Department of Radiology, University of Granada, Granada (Spain); Olea, N. [Laboratory of Medical Investigations, San Cecilio University Hospital, CIBER de Epidemiologia y Salud Publica (CIBERESP) (Spain); Department of Radiology, University of Granada, Granada (Spain); Nunez, M.I., E-mail: isabeln@ugr.es [Department of Radiology, University of Granada, Granada (Spain)

    2010-07-15

    Childhood exposure to physical contamination, including non-ionizing radiation, has been implicated in numerous diseases, raising concerns about the widespread and increasing sources of exposure to this type of radiation. The primary objective of this review was to analyze the current state of knowledge on the association between environmental exposure to non-ionizing radiation and the risk of childhood leukemia. Scientific publications between 1979 and 2008 that include examination of this association have been reviewed using the MEDLINE/PubMed database. Studies to date have not convincingly confirmed or ruled out an association between non-ionizing radiation and the risk of childhood leukemia. Discrepancies among the conclusions of the studies may also be influenced by confounding factors, selection bias, and misclassification. Childhood defects can result from genetic or epigenetic damage and from effects on the embryo or fetus, which may both be related to environmental exposure of the parent before conception or during the pregnancy. It is therefore critical for researchers to define a priori the type and 'window' of exposure to be assessed. Methodological problems to be solved include the proper diagnostic classification of individuals and the estimated exposure to non-ionizing radiation, which may act through various mechanisms of action. There appears to be an urgent need to reconsider exposure limits for low frequency and static magnetic fields, based on combined experimental and epidemiological research into the relationship between exposure to non-ionizing radiation and adverse human health effects.

  6. Exposure to electromagnetic fields (non-ionizing radiation) and its relationship with childhood leukemia: a systematic review.

    Science.gov (United States)

    Calvente, I; Fernandez, M F; Villalba, J; Olea, N; Nuñez, M I

    2010-07-15

    Childhood exposure to physical contamination, including non-ionizing radiation, has been implicated in numerous diseases, raising concerns about the widespread and increasing sources of exposure to this type of radiation. The primary objective of this review was to analyze the current state of knowledge on the association between environmental exposure to non-ionizing radiation and the risk of childhood leukemia. Scientific publications between 1979 and 2008 that include examination of this association have been reviewed using the MEDLINE/PubMed database. Studies to date have not convincingly confirmed or ruled out an association between non-ionizing radiation and the risk of childhood leukemia. Discrepancies among the conclusions of the studies may also be influenced by confounding factors, selection bias, and misclassification. Childhood defects can result from genetic or epigenetic damage and from effects on the embryo or fetus, which may both be related to environmental exposure of the parent before conception or during the pregnancy. It is therefore critical for researchers to define a priori the type and "window" of exposure to be assessed. Methodological problems to be solved include the proper diagnostic classification of individuals and the estimated exposure to non-ionizing radiation, which may act through various mechanisms of action. There appears to be an urgent need to reconsider exposure limits for low frequency and static magnetic fields, based on combined experimental and epidemiological research into the relationship between exposure to non-ionizing radiation and adverse human health effects.

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

    Science.gov (United States)

    2017-01-09

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

  8. Genetic Mediators of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Krull, Kevin R.; Bhojwani, Deepa; Conklin, Heather M.; Pei, Deqing; Cheng, Cheng; Reddick, Wilburn E.; Sandlund, John T.; Pui, Ching-Hon

    2013-01-01

    Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive problems, with significant interindividual variability in outcome. This study examined genetic polymorphisms associated with variability in neurocognitive outcome. Patients and Methods Neurocognitive outcomes were evaluated at the end of therapy in 243 survivors treated on an institutional protocol featuring risk-adapted chemotherapy without prophylactic cranial irradiation. Polymorphisms in genes related to pharmacokinetics or pharmacodynamics of antileukemic agents, drug metabolism, oxidative stress, and attention problems in noncancer populations were examined as predictors of outcome, using multiple general linear models and controlling for age at diagnosis, sex, race, and treatment intensity. Results Compared with national norms, the cohort demonstrated significantly higher rates of problems on direct assessment of sustained attention (P = .01) and on parent ratings of attention problems (P = .02). Children with the A2756G polymorphism in methionine synthase (MS) were more likely to demonstrate deficits in attentiveness (P = .03) and response speed (P = .02), whereas those with various polymorphisms in glutathione S-transferase demonstrated increased performance variability (P = .01) and reduced attentiveness (P = .003). Polymorphisms in monoamine oxidase (T1460CA) were associated with increased attention variability (P = .03). Parent-reported attention problems were more common in children with the Cys112Arg polymorphism in apoliopoprotein E4 (P = .01). Conclusion These results are consistent with our previous report of association between attention problems and MS in an independent cohort of long-term survivors of childhood ALL treated with chemotherapy only. The results also raise the possibility of an impact from genetic predispositions related to oxidative stress and CNS integrity. PMID:23650422

  9. Mechanism of Leukemia Relapse: Novel Insights on Old Problem%白血病复发的机制:老问题,新视角

    Institute of Scientific and Technical Information of China (English)

    吴克复; 郑国光; 马小彤; 宋玉华; 竺晓凡

    2011-01-01

    复发是根治白血病的瓶颈,困扰了几代血液学工作者.21世纪初人类微生物基因组计划(Human Microbiome Project,HMP)的研究进展表明,人体是以人类细胞为核心与共生微生物共同构成的超有机体;对内源性逆转录病毒和朊病毒蛋白(prion protein,PrP)的逐步阐明提示了共进化微生物对人类健康的可能影响;近年来对隧道纳米管道(tunneling nanotubes,TNT)在细胞间通讯和物质传递中作用的初步阐明提示了癌基因、癌蛋白在细胞间传播的新途径;以及对体内细胞融合作用和意义的深入探讨及供体细胞白血病的报道等多方面的研究进展,为白血病复发机制的研究提供了新的视角.作者结合多年来的工作从新的视角探讨影响白血病复发的可能机制,提出存在微小残留病和细胞间致癌因子传递两类复发机制的假设.%Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias.The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms.The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health.Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials.The role and significance of in vivo cell fusion have been studied in more detail.On the other hand, donor cell leukemia was reported.All of these approaches provide novel insights for studying the mechanism of leukemia relapse.Based on previous work,the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic

  10. Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    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.

  11. Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    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.

  12. Value of routine bone marrow examination in pediatric acute myeloid leukemia (AML) : A study of the Dutch Childhood Oncology Group (DCOG)

    NARCIS (Netherlands)

    Hageman, Ilse M. G.; Peek, Annemarie M. L.; de Haas, Valerie; Damen-Korbijn, Carin M.; Kaspers, Gertjan J. L.

    2012-01-01

    Background The outcome of the treatment of pediatric acute myeloid leukemia (AML) is still disappointing, due to relatively high treatment-related mortality and relapse rates (3040%). Past treatment protocols have called for routine screening via bone marrow aspiration (BMA) after achievement of fir

  13. 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

  14. A comparison of spatial clustering and cluster detection techniques for childhood leukemia incidence in Ohio, 1996 – 2003

    Directory of Open Access Journals (Sweden)

    Wheeler David C

    2007-03-01

    Full Text Available Abstract Background Spatial cluster detection is an important tool in cancer surveillance to identify areas of elevated risk and to generate hypotheses about cancer etiology. There are many cluster detection methods used in spatial epidemiology to investigate suspicious groupings of cancer occurrences in regional count data and case-control data, where controls are sampled from the at-risk population. Numerous studies in the literature have focused on childhood leukemia because of its relatively large incidence among children compared with other malignant diseases and substantial public concern over elevated leukemia incidence. The main focus of this paper is an analysis of the spatial distribution of leukemia incidence among children from 0 to 14 years of age in Ohio from 1996–2003 using individual case data from the Ohio Cancer Incidence Surveillance System (OCISS. Specifically, we explore whether there is statistically significant global clustering and if there are statistically significant local clusters of individual leukemia cases in Ohio using numerous published methods of spatial cluster detection, including spatial point process summary methods, a nearest neighbor method, and a local rate scanning method. We use the K function, Cuzick and Edward's method, and the kernel intensity function to test for significant global clustering and the kernel intensity function and Kulldorff's spatial scan statistic in SaTScan to test for significant local clusters. Results We found some evidence, although inconclusive, of significant local clusters in childhood leukemia in Ohio, but no significant overall clustering. The findings from the local cluster detection analyses are not consistent for the different cluster detection techniques, where the spatial scan method in SaTScan does not find statistically significant local clusters, while the kernel intensity function method suggests statistically significant clusters in areas of central, southern

  15. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy

    Directory of Open Access Journals (Sweden)

    Di Pietro Cinzia

    2010-07-01

    Full Text Available Abstract Background According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML patients in apparent complete remission (CR after chemotherapy induction may be classified into three groups: (i normally responsive; (ii chemoresistant; (iii highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM in these phenotypic features. Methods To investigate the molecular bases of the differential chemosensitivity of bone marrow hematopoietic stem cells (HSC in CR AML patients, and the relationship between chemosensitivity, mobilizing activity and relapse rates, we analyzed their AM expression profile by performing Real Time RT-PCR of 84 AM genes in CD34+ pools from the two extreme classes of patients (i.e., chemoresistant and highly chemosensitive, and compared them with normal controls. Results The AM expression profiles of patients highlighted features that could satisfactorily explain their in vitro chemoresponsive phenotype: specifically, in chemoresistant patients we detected up regulation of antiapoptotic BIRC genes and down regulation of proapoptotic APAF1, FAS, FASL, TNFRSF25. Interestingly, our analysis of the AM network showed that the dysregulated genes in these patients are characterized by high network centrality (i.e., high values of betweenness, closeness, radiality, stress and high involvement in drug response. Conclusions AM genes represent critical nodes for the proper execution of cell death following pharmacological induction in patients. We propose that their

  16. Viremia during pregnancy and risk of childhood leukemia and lymphomas in the offspring: Nested case-control study.

    Science.gov (United States)

    Bzhalava, Davit; Hultin, Emilie; Arroyo Mühr, Laila Sara; Ekström, Johanna; Lehtinen, Matti; de Villiers, Ethel-Michele; Dillner, Joakim

    2016-05-01

    A possible role for infections of the pregnant mother in the development of childhood acute leukemias and lymphomas has been suggested. However, no specific infectious agent has been identified. Offspring of 74,000 mothers who had serum samples taken during pregnancy and stored in a large-scale biobank were followed up to the age of 15 years (750,000 person years) through over-generation linkages between the biobank files, the Swedish national population and cancer registers to identify incident leukemia/lymphoma cases in the offspring. First-trimester sera from mothers of 47 cases and 47 matched controls were retrieved and analyzed using next generation sequencing. Anelloviruses were the most common viruses detected, found in 37/47 cases and in 40/47 controls, respectively (OR: 0.6, 95% CI: 0.2-1.9). None of the detected viruses was associated with leukemia/lymphoma in the offspring. Viremia during pregnancy was common, but no association with leukemia/lymphoma risk in the offspring was found.

  17. Maternal benzene exposure during pregnancy and risk of childhood acute lymphoblastic leukemia: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Yanfeng Zhou

    Full Text Available The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.Relevant studies up to September 1st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR with 95% confidence interval (CI for ALL was 1.25 (1.09, 1.45 for solvent, 1.23 (1.02, 1.47 for paint, 1.42 (1.10, 1.84 for petroleum exposure, and 0.99 (0.93, 1.06 for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.

  18. Technical relapsed testicular irradiation for acute lymphoblastic leukemia; Tecnica de irradiacion para testiculos en recidiva de leucemia linfoblastica aguda

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-07-01

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  19. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  20. White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Fiona S Anderson

    2008-03-01

    Full Text Available Fiona S Anderson1, Alicia S Kunin-Batson1, Joanna L Perkins2, K Scott Baker31Divisions of Pediatric Clinical Neuroscience; 2Department of Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, MN, USA and 3Hematology/Oncology/BMT, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USAAbstract: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT. Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1 were significantly lower (t = 2.26, p = 0.03 than composite gray matter scores (mean = 102.5. Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035. Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.Keywords: late effects of cancer treatment, leukemia, neuropsychology, white matter, brain function

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Stefano Mattioli

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

  3. Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

    Science.gov (United States)

    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Hasani, Seyed-Shahab-Adin; Naderi, Majid; Sadeghi-Bojd, Simin; Taheri, Mohsen

    2017-03-04

    We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

  4. Sarcoma granulocítico multicêntrico como recidiva de leucemia mieloide aguda Multicentric granulocytic sarcoma as relapse of acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Taciana G. S. Aguiar

    2009-01-01

    Full Text Available Sarcoma granulocítico (SG é um tumor sólido extramedular, constituído por células precursoras de granulócitos. É geralmente associado a leucemia mieloide aguda ou raramente a outras desordens mieloproliferativas. O tumor geralmente ocorre precedendo uma leucemia mieloide aguda, durante o seu curso ou após a remissão ter sido alcançada. O prognóstico é pobre e tem como principais modalidades terapêuticas a quimioterapia e a radioterapia. Relata- se um caso de SG multicêntrico, de evolução rápida, com acometimento difuso de pele, mamas, gânglios linfáticos, tecido celular subcutâneo e líquor, em mulher de 45 anos, fora de tratamento para leucemia mieloide aguda e em remissão hematológica há 18 meses. A paciente apresentava dor intensa em membro inferior direito há uma semana e estava em anticoagulação oral há seis meses por trombose venosa profunda neste membro. Diagnosticado o SG, a paciente foi tratada com radioterapia e quimioterapia com boa resposta. Após três meses de seguimento, em vigência do tratamento quimioterápico, evoluiu com recidiva do SG neste membro, associado ao acometimento das mamas e posteriormente do sistema nervoso central, evoluindo para óbito em aplasia e sepses.Granulocytic sarcoma is an extramedullary solid tumor consisting of immature granulocytic cells. It is often associated with acute myelogenous leukemia and more rarely with other myeloproliferative disorders. The tumor generally occurs before acute myeloid leukemia, during its course or after disease remission. It has a poor prognosis with the main therapeutic options being chemotherapy and radiotherapy. A multicentric accelerated case of granulocytic sarcoma of a 45- year- old woman with diffuse skin, breast, lymphatic ganglia and subcutaneous tissue presentations no longer undergoing treatment for acute myeloid leukemia and in hematologic remission for 18 months is reported. The patient presented with severe pain of right lower

  5. Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review%嵌合抗原受体T细胞治疗儿童急性B淋巴细胞白血病异基因造血干细胞移植后复发一例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    左英熹; 王静波; 陆爱东; 贾月萍; 吴珺; 董陆佳; 张隆基; 张乐萍

    2016-01-01

    目的 探讨嵌合抗原受体(CAR)T细胞技术治疗儿童急性B淋巴细胞白nL病(B-ALL)的临床疗效和不良反应.方法 报道1例CAR-T细胞治疗儿童B-ALL异基因造血干细胞移植(allo-HSCT)后复发患者,并复习相关文献.结果 1例伴TEL-AML1融合基因阳性11岁B-ALL患儿,规律化疗后早期复发,于第2次完全缓解(CR)期给予allo-HSCT.治疗后骨髓微小残留病(MRD)反复阳性,化疗以及供者淋巴细胞输注(DLI)治疗无明显疗效,故给予供者来源的抗CD19的CAR-T细胞输注.该患儿经输注CAR-T细胞1×106/kg后骨髓MRD转阴,后又反复输注3次CAR-T细胞[(0.83~1.65)×106/kg],患儿持续无病生存达10个月,随后输注CAR-T细胞2次,监测外周血TEL-AML1融合基因拷贝持续升高,最终骨髓复发,因脑出血死亡.输注CAR-T细胞的主要不良反应为细胞因子释放综合征.结论 抗CD19的CAR-T细胞技术治疗复发B-ALL安全有效,为复发及难治性B-ALL患儿提供了新的治疗手段.%Objective To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL).Methods A relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T,and the related literatures were reviewed.Result An l 1-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy.During the second remission,the patient received haploidentical allo-HSCT.She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions.She received an experimental donor-derived fourth generation CD19 CAR-T therapy.After infusion of 1 × 106/kg CAR-T cells,she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative.Then three maintenance of CAR-T cell infusions [(0.83-1.65) × 106/kg] was administered,and the disease

  6. 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...... were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM......1 and GSTT1 into poor (0 or 1 gene copy)-and good metabolizers (at least 2 gene copies)-showed that the poor metabolizers had a trend toward a better outcome (event-free survival = 91.8%) compared with the good metabolizers (event-free survival = 83.2%). Similarly, in the adjusted analysis the good...

  7. The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gruhn, Bernd; Naumann, Thomas; Gruner, Dorothee; Walther, Mario; Wittig, Susan; Becker, Sabine; Beck, James F; Sonnemann, Jürgen

    2013-10-01

    This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.

  8. Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

    Directory of Open Access Journals (Sweden)

    Burmeister Thomas

    2012-04-01

    Full Text Available Abstract This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11(p11.2;q23 with MLL-AF10 and the second a t(11;19(q23;p13.1 with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis. Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD, based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, both patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.

  9. Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.

    Science.gov (United States)

    Kako, Shinichi; Kanda, Yoshinobu; Sato, Tomohiko; Goyama, Susumu; Noda, Naohiro; Shoda, Eriko; Oshima, Kumi; Inoue, Morihiro; Izutsu, Koji; Watanabe, Takuro; Motokura, Toru; Chiba, Shigeru; Fukayama, Masashi; Kurokawa, Mineo

    2007-05-01

    Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL.

  10. Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

    Science.gov (United States)

    Hyakuna, Nobuyuki; Shimomura, Yasuto; Watanabe, Arata; Taga, Takashi; Kikuta, Atsushi; Matsushita, Takeji; Kogawa, Kazuhiro; Kawakami, Chihiro; Horikoshi, Yasuo; Iwai, Tsuyako; Okamoto, Yasuhiro; Tsurusawa, Masahito; Asami, Keiko

    2014-01-01

    Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

  11. Aurora kinases in childhood acute leukemia: The promise of aurora B as therapeutic target

    NARCIS (Netherlands)

    S.A. Hartsink-Segers (S.); C.M. Zwaan (Michel); C. Exalto (Carla); M.W.J. Luijendijk (M. W J); V. Calvert (V.); E.F. Petricoin (Emanuel F.); W.E. Evans (William); D. Reinhardt (Dirk); V. de Haas (Valerie); M. Hedtjärn (M.); B.R. Hansen (B.); T. Koch (T.); H.N. Caron (Huib); R. Pieters (Rob); M.L. den Boer (Monique)

    2013-01-01

    textabstractWe investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse ph

  12. Analysis of childhood leukemia mortality trends in Brazil, from 1980 to 2010

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    Franciane F. Silva

    2014-12-01

    Full Text Available OBJECTIVE: Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010. METHODS: This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%. RESULTS: Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually, while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females. CONCLUSIONS: The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis.

  13. High resolution melting curve analysis, a rapid and affordable method for mutation analysis in childhood acute myeloid leukemia

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    Yin eLiu

    2014-09-01

    Full Text Available Background: Molecular genetic alterations with prognostic significance have been described in childhood acute myeloid leukemia (AML. The aim of this study was to establish cost-effective techniques to detect mutations of FMS-like tyrosine kinase 3 (FLT3, Nucleophosmin 1 (NPM1, and a partial tandem duplication within the mixed lineage leukemia (MLL-PTD genes in childhood AML. Procedure: Ninety-nine children with newly diagnosed AML were included in this study. We developed a fluoresent dye SYTO-82 based high resolution melting curve (HRM anaylsis to detect FLT3 internal tandem duplication (FLT3-ITD, FLT3 tyrosine kinase domain (FLT3-TKD and NPM1 mutations. MLL-PTD was screened by real-time quantitative PCR. Results: The HRM methodology correlated well with gold standard Sanger sequencing with less cost. Among the 99 patients studied, the FLT3-ITD mutation was associated with significantly worse event free survival (EFS. Patients with the NPM1 mutation had significantly better EFS and overall survival. However, HRM was not sensitive enough for minimal residual disease monitoring. Conclusions: HRM was a rapid and efficient method for screening of FLT3 and NPM1 gene mutations. It was both affordable and accurate, especially in resource underprivileged regions. Our results indicated that HRM could be a useful clinical tool for rapid and cost effective screening of the FLT3 and NPM1 mutations in AML patients.

  14. Effects of Maternal Diet During Pregnancy on the Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review.

    Science.gov (United States)

    Abiri, Behnaz; Kelishadi, Roya; Sadeghi, Homa; Azizi-Soleiman, Fatemeh

    2016-10-01

    Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children that can be affected by maternal diet. The aim of this study was to evaluate maternal dietary risk factors of ALL. We searched MEDLINE, Cochrane Library, Springer Link, Wiley Online, Science Direct, Mosby, ISI Web of Science, OVID, ProQuest, and Scopus from database inception until February 2, 2016. Two reviewers scanned titles, abstracts, and keywords of articles after excluding duplicates. We included case-control studies evaluating the relationship between maternal diet during pregnancy and childhood ALL. The search resulted in 2,940 papers, of which 11 full-text articles met the criteria for inclusion in the review and were analyzed. The finding of these studies suggest that maternal diet composed largely of vegetables, fruits, and protein sources before and during pregnancy can reduce the risk of ALL in offspring. Maternal alcohol intake had no effect. Nevertheless, inherent limitations of case-control studies like measurement error, random error, recall bias, and selection bias preclude conclusive evidence. Persuading pregnant women to follow a healthy diet rich in fruits, vegetables, and protein may reduce the risk of childhood ALL. Avoiding alcohol intake seems prudent.

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

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

    therapy with a precise and reproducible clone-specific PCR technique. The median MRD-D15 and MRD-PI were 0.50% (75% range 0.0088.1%) and 0.014% (75% range 0.001-2.0%), respectively, and these levels correlated significantly (n = 29, rs = 0.75, P ... combined monitoring of in vitro drug resistance and residual leukemia early during chemotherapy could offer new ways to classify patients and stratify the intensity of therapy. Udgivelsesdato: 2001-Jul...

  16. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

  17. Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

    Science.gov (United States)

    2013-06-03

    Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  18. Phase 1 and Extension Study of Clofarabine plus Cyclophosphamide in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

    Science.gov (United States)

    Faderl, S; Balakrishnan, K; Thomas, DA; Ravandi, F; Borthakur, G; Burger, J; Ferrajoli, A; Cortes, J; O’Brien, S; Kadia, T; Feliu, J; Plunkett, W; Gandhi, V; Kantarjian, HM

    2014-01-01

    Background Clofarabine is a nucleoside analog with activity in children with ALL. Based on the hypothesis that clofarabine inhibits DNA repair following exposure to DNA damaging agents, we designed a phase 1 and extension study to evaluate the combination of clofarabine with cyclophosphamide in adult patients with relapsed/refractory ALL. Methods The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD). Results Fifty patients with a median age of 30 years (range 21–72 years) were enrolled of whom 30 patients were part of the phase 1 group. Clofarabine 40 mg/m2 iv daily x 3 days and cyclophosphamide 200 mg/m2 iv q 12 hours x 3 days were established as the MTD. Dose limiting toxicities were diarrhea, transaminase elevations, and skin rashes. The response rate of the whole study group was 14% including 10% of patients who achieved complete remission (CR) or CR without platelet recovery. Three responses occurred in patients with primary refractory disease. Early mortality (< 30 days) was 6%. The median response duration was 69 days (range 5–315 days). Median overall survival was about 3 months. Compared to day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Conclusions The combination of clofarabine plus cyclophosphamide at the doses used in this study and in a group of heavily pretreated patients with ALL is only moderately effective. Other doses, alternative schedules, or a more favorable patient population may achieve better results. (Word count: 248) PMID:24440659

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study

    Directory of Open Access Journals (Sweden)

    Jae-Ho Yoon

    2017-01-01

    Full Text Available Abstract Wilms’ tumor gene 1 (WT1 expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen for WT1 monitoring. High WT1 expression (>120 copies/104 ABL1 after consolidation and at early period (3 months after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40 showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001 and inferior disease free survival (62.8 vs. 91.4%, P < 0.001. Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001 and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001 were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention. Trial registration Clinical Research Information Service (CRIS, KCT0002079

  1. More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

    Science.gov (United States)

    A study suggests that at least some children diagnosed with acute lymphoblastic leukemia who respond poorly to initial chemotherapy may do better if they receive additional chemotherapy rather than a stem cell transplant.

  2. Disruption of Learning Processes by Chemotherapeutic Agents in Childhood Survivors of Acute Lymphoblastic Leukemia and Preclinical Models

    Directory of Open Access Journals (Sweden)

    Emily B. Bisen-Hersh, Philip N. Hineline, Ellen A. Walker

    2011-01-01

    Full Text Available Objective: With the survival rate of acute lymphoblastic leukemia (ALL surpassing 90 percent within this decade, new research is emerging in the field of late effects. A review of the research investigating the relationship of treatment regimens for ALL to specific late effect deficits, underlying mechanisms, and possible remediation is warranted to support continued studies.Methods: The clinical literature was briefly surveyed to describe the occurrence and topography of late effects, specifically neurocognitive deficits. Additionally, the preclinical literature was reviewed to uncover potential underlying mechanisms of these deficits. The advantages of using rodent models to answer these questions are outlined, as is an assessment of the limited number of rodent models of childhood cancer treatment.Results: The literature supports that childhood survivors of ALL exhibit academic difficulties and are more likely to be placed in a special education program. Behavioral evidence has highlighted impairments in the areas of attention, working memory, and processing speed, leading to a decrease in full scale IQ. Neurophysiological and preclinical evidence for these deficits has implicated white matter abnormalities and acquired brain damage resulting from specific chemotherapeutic agents commonly used during treatment.Conclusions: The exact role of chemotherapeutic agents in learning deficits remains mostly unknown. Recommendations for an improved rodent model of learning deficits in childhood cancer survivors are proposed, along with suggestions for future directions in this area of research, in hopes that forthcoming treatment regimens will reduce or eliminate these types of impairments.

  3. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood.

    Science.gov (United States)

    Heck, Julia E; Park, Andrew S; Qiu, Jiaheng; Cockburn, Myles; Ritz, Beate

    2014-07-01

    There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children leukemia associated with one interquartile range increase in air toxic exposure. Risk of ALL was elevated with 3(rd) trimester exposure to polycyclic aromatic hydrocarbons (OR=1.16, 95% CI 1.04, 1.29), arsenic (OR=1.33, 95% CI 1.02, 1.73), benzene (OR=1.50, 95% CI 1.08, 2.09), and three other toxics related to fuel combustion. Risk of AML was increased with 3rd trimester exposure to chloroform (OR=1.30, 95% CI 1.00, 1.69), benzene (1.75, 95% CI 1.04, 2.93), and two other traffic-related toxics. During the child's first year, exposure to butadiene, ortho-xylene, and toluene increased risk for AML and exposure to selenium increased risk for ALL. Benzene is an established cause of leukemia in adults; this study supports that ambient exposures to this and other chemicals in pregnancy and early life may also increase leukemia risk in children.

  5. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    Science.gov (United States)

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  6. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

  7. Medical progress, psychological factors and global care of the patient: lessons from the treatment of childhood leukemia

    Directory of Open Access Journals (Sweden)

    Girolamo Digilio

    2013-03-01

    Full Text Available The history of treatment of childhood leukemia is a meaningful model of ethical, bioethical and organizational repercussions of medical progress. Specifically, it has provided precious indications and very useful tools to cope with several of the more important problems of modern medicine: the value of controlled randomized studies; the risks of intense medicalization impairing the quality of care; the importance of a valid doctor-patient relationship; the psycho-emotive involvement of the pediatric staff; and last but not least, the need of an unrelenting effort of humanization of the procedures and environments, hand in hand with the frequent adjustments of the protocols according to scientific and technological progress. Finally, the authors comment upon the first cures (1962-1966 observed in the Pediatrics Clinic of the Sapienza University of Rome.

  8. Phase 1 trial of gemtuzumab ozogamicin in combination with enocitabine and daunorubicin for elderly patients with relapsed or refractory acute myeloid leukemia: Japan Adult Leukemia Study Group (JALSG)-GML208 study.

    Science.gov (United States)

    Ito, Yoshikazu; Wakita, Atsushi; Takada, Satoru; Mihara, Masahiro; Gotoh, Moritaka; Ohyashiki, Kazuma; Ohtake, Shigeki; Miyawaki, Shuichi; Ohnishi, Kazunori; Naoe, Tomoki

    2012-10-01

    We conducted a phase 1 study of a combination of gemtuzumab ozogamicin (GO) plus conventional chemotherapy in elderly patients (≥ 65 years old) with relapsed or refractory CD33-positive acute myeloid leukemia (AML). Patients received a standard dose of enocitabine (200 mg/m² × 8 days) and daunorubicin (30 mg/m² × days 1-3) plus an escalating dose of GO (1.5-5 mg/m² on day 4). The dose escalation of GO was done according to a standard 3 + 3 design following a modified Fibonacci sequence. No dose-limiting toxicities were observed in three patients (median age, 71) at level 1 (1.5 mg/m²) or in three patients (median age, 73) at level 2 (3 mg/m²). Neither veno-occlusive diseases nor sinusoidal obstructive syndromes were noted at either level. However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5 mg/m²) in order to avoid possibly more severe adverse effects, and also because all six patients experienced grade 4 myelosuppression, with complete remission in three. This study showed that 3 mg/m² of GO in combination with enocitabine and daunorubicin may be a recommendable dose for a phase 2 study in Japanese elderly patients with CD33-positive AML. The study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ) as UMIN000002603.

  9. Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood.

    Science.gov (United States)

    Girard, Pauline; Auquier, Pascal; Barlogis, Vincent; Contet, Audrey; Poiree, Maryline; Demeocq, François; Berbis, Julie; Herrmann, Iris; Villes, Virginie; Sirvent, Nicolas; Kanold, Justyna; Chastagner, Pascal; Chambost, Hervé; Plantaz, Dominique; Michel, Gérard

    2013-07-01

    Corticosteroid can induce osteonecrosis in children with leukemia. Few studies have been designed to assess the influence of a wide range of cumulative steroid dose on this side effect. Prevalence, risk factors of symptomatic osteonecrosis and its impact on adults' Quality of Life were assessed in 943 patients enrolled in the French "Leucémies de l'Enfant et de l'Adolescent" (LEA) cohort of childhood leukemia survivors. During each medical visit, data on previous osteonecrosis diagnosis were retrospectively collected. Patients without a history but with suggestive symptoms were investigated with magnetic resonance imaging. The total steroid dose in equivalent of prednisone was calculated for each patient and its effect on osteonecrosis occurrence was studied in multivariate models. Cumulative incidence was 1.4% after chemotherapy alone versus 6.8% after transplantation (Posteonecrosis. A higher post-transplant steroid dose and age over ten years at time of transplantation were significant factors in the transplanted group. With patients grouped according to steroid dose quartile, cumulative incidence of osteonecrosis reached 3.8% in the chemotherapy group for a dose beyond 5835 mg/m(2) and 23.8% after transplantation for a post-transplant dose higher than 2055 mg/m(2). Mean physical composite score of Quality of Life was 44.3 in patients with osteonecrosis versus 54.8% in patients without (Posteonecrosis, a rare late effect with a strong negative impact on physical domains of Quality of Life.

  10. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings.......More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  11. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    Science.gov (United States)

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  12. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  13. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event

    OpenAIRE

    Quéré, R.; Andradottir, S; Brun, A C M; Zubarev, R.A.; Karlsson, G; Olsson, K.; Magnusson, M.; Cammenga, J; Karlsson, S.

    2010-01-01

    Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the ...

  14. 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

  15. 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 of cardiomyo...

  16. Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Juul, Anders; Lausten-Thomsen, Ulrik;

    2011-01-01

    Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrena...

  17. 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

  18. FLT3 Gene Mutation in Childhood Acute Leukemia: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Zefarina Zulkafli

    2014-01-01

    Full Text Available Introduction. FLT3 is a tyrosine kinase receptor involved in the proliferation and differentiation of hematopoietic stem cells. There are two types of common FLT3 gene mutation, internal tandem duplication and the D835 mutation, which are known to be associated with a poor clinical outcome in acute leukemia patients. Methods. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD in 38 pediatric patients diagnosed with acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML in Hospital Universiti Sains Malaysia. DNA extraction was done from archive bone marrow samples to determine FLT3-ITD mutations using polymerase chain reaction. Results. In this pediatric series, the age ranges were 2–14 years. However, no FLT3-ITD mutations were detected in any of the samples. Conclusion. This preliminary study suggested that the incidence of FLT3 gene mutation most probably was very low in pediatrics patients diagnosed with acute leukemia. A further study with larger number of patient samples is necessary to confirm the findings and to further appreciate the prognostic value of FLT3-ITD mutation among pediatrics patients.

  19. 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

  20. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia : a retrospective international study

    NARCIS (Netherlands)

    Inaba, Hiroto; Zhou, Yinmei; Abla, Oussama; Adachi, Souichi; Auvrignon, Anne; Beverloo, H. Berna; de Bont, Eveline; Chang, Tai-Tsung; Creutzig, Ursula; Dworzak, Michael; Elitzur, Sarah; Fynn, Alcira; Forestier, Erik; Hasle, Henrik; Liang, Der-Cherng; Lee, Vincent; Locatelli, Franco; Masetti, Riccardo; De Moerloose, Barbara; Reinhardt, Dirk; Rodriguez, Laura; Van Roy, Nadine; Shen, Shuhong; Taga, Takashi; Tomizawa, Daisuke; Yeoh, Allen E. J.; Zimmermann, Martin; Raimondi, Susana C.

    2015-01-01

    Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age 50 chromosomes (n=44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%),

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

    Science.gov (United States)

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

  2. 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

  3. 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

  4. Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Jasmine Healy

    2010-01-01

    Full Text Available Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL. We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P=.017 and CDKN2B rs36229158 (P=.022 that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases.

  5. Neurocognitive Outcomes in Long-term Survivors of Childhood Acute Lymphoblastic Leukemia Treated on Contemporary Treatment Protocols: A Systematic Review

    Science.gov (United States)

    Cheung, Yin Ting; Krull, Kevin R.

    2015-01-01

    The intensified administration of chemotherapeutic drugs has gradually replaced cranial radiation therapy (CRT) for the treatment of childhood acute lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive impairment in ALL survivors, there is a paucity of literature that evaluates the persistence of neurocognitive deficits in long-term survivors of pediatric ALL who were treated with contemporary chemotherapy-only protocols. Results from this systematic review concurred to the probable cognitive-sparing effect of chemotherapy-based protocols over CRT in long-term survivors. However, coupled with multiple intrinsic and extrinsic factors, survivors who received chemotherapy treatment still suffered from apparent cognitive impairment, particularly in the attention and executive function domains. Notably, there is evidence to suggest that the late neurotoxic effect of methotrexate on survivors’ neurocognitive performance may be dose-related. This review also recommends future pharmacokinetic, neuroimaging and genetic studies to illuminate the multifactorial nature of this subject matter and discusses the potential value of neurochemical, physiological, inflammatory and genetic markers for the prediction of susceptibility to neurocognitive impairment in long-term survivors of childhood ALL. PMID:25857254

  6. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    Science.gov (United States)

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

  7. Hairy Cell Leukemia Treatment Option Overview

    Science.gov (United States)

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia Treatment (PDQ®)–Patient Version General Information About Hairy Cell Leukemia Go to Health Professional Version Key Points ...

  8. Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Martin Feller

    Full Text Available BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL. METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004, remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060 after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032 and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141 and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019, with some evidence for an effect modification (p-value for interaction  = 0.040. CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

  9. A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants

    Science.gov (United States)

    Singh, Sandeep K.; Lupo, Philip J.; Scheurer, Michael E.; Saxena, Anshul; Kennedy, Amy E.; Ibrahimou, Boubakari; Barbieri, Manuel Alejandro; Mills, Ken I.; McCauley, Jacob L.; Okcu, Mehmet Fatih; Dorak, Mehmet Tevfik

    2016-01-01

    Abstract Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex. The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1∗01 and confirmed the previously reported male-specific association with DQA1∗01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels. Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by

  10. Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study

    Science.gov (United States)

    Krull, Kevin R.; Brinkman, Tara M.; Li, Chenghong; Armstrong, Gregory T.; Ness, Kirsten K.; Srivastava, Deo Kumar; Gurney, James G.; Kimberg, Cara; Krasin, Matthew J.; Pui, Ching-Hon; Robison, Leslie L.; Hudson, Melissa M.

    2013-01-01

    Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. PMID:24190124

  11. Childhood Cancer Genomics (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the genomics of childhood cancer. The summary describes the molecular subtypes for specific pediatric cancers and their associated clinical characteristics, the recurring genomic alterations that characterize each subtype at diagnosis or relapse, and the therapeutic and prognostic significance of the genomic alterations. The genomic alterations associated with brain tumors, kidney tumors, leukemias, lymphomas, sarcomas, and other cancers are discussed.

  12. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    Science.gov (United States)

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  13. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); 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 Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

    Science.gov (United States)

    Quéré, R; Andradottir, S; Brun, A C M; Zubarev, R A; Karlsson, G; Olsson, K; Magnusson, M; Cammenga, J; Karlsson, S

    2011-03-01

    Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

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

    Science.gov (United States)

    Marshall, G M; Dalla Pozza, L; Sutton, R; Ng, A; de Groot-Kruseman, H A; van der Velden, V H; Venn, N C; van den Berg, H; de Bont, E S J M; Maarten Egeler, R; 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; Révész, T; Alvaro, F; Suppiah, R; Norris, M D; Pieters, R

    2013-07-01

    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 identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

  16. Probability estimates for the unique childhood leukemia cluster in Fallon, Nevada, and risks near other U.S. Military aviation facilities.

    OpenAIRE

    2004-01-01

    A unique cluster of childhood leukemia has recently occurred around the city of Fallon in Churchill County, Nevada. From 1999 to 2001, 11 cases were diagnosed in this county of 23,982 people. Exposures related to a nearby naval air station such as jet fuel or an infectious agent carried by naval aviators have been hypothesized as potential causes. The possibility that the cluster could be attributed to chance was also considered. We used data from the Surveillance, Epidemiology, and End Resul...

  17. Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia

    OpenAIRE

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

    2008-01-01

    The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case–control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls

  18. 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...

  19. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.

    Science.gov (United States)

    Schroeder, Thomas; Rachlis, Elena; Bug, Gesine; Stelljes, Matthias; Klein, Stefan; Steckel, Nina Kristin; Wolf, Dominik; Ringhoffer, Mark; Czibere, Akos; Nachtkamp, Kathrin; Dienst, Ariane; Kondakci, Mustafa; Stadler, Michael; Platzbecker, Uwe; Uharek, Lutz; Luft, Thomas; Fenk, Roland; Germing, Ulrich; Bornhäuser, Martin; Kröger, Nicolaus; Beelen, Dietrich W; Haas, Rainer; Kobbe, Guido

    2015-04-01

    To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

  20. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    Science.gov (United States)

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  1. Prognostic value of bone marrowhematogones in childhood B-lineage acute lymphoblastic leukemia%原血细胞对于儿童急性B淋巴细胞白血病预后判断的价值

    Institute of Scientific and Technical Information of China (English)

    王月芳; 江咏梅; 高举; 周平; 张鸽

    2016-01-01

    ObjectiveTo study the prognostic value of hematogones (HGs) for childhood B-lineage acute lymphoblastic leukemia (B-ALL) during consolidation chemotherapy.MethodsA retrospective analysis was conducted for 196 children with newly-diagnosed B-ALL. They were divided into high-risk group (n=55), intermediate-risk group (n=69), and low-risk group (n=72) by risk stratiifcation, and into complete remission group (n=165) and relapse group (n=31) by clinical outcome. The European BIOMED-1 standard lfow cytometry for minimal residual disease (MRD) was used to determine the number of HGs during consolidation chemotherapy. The Kaplan-Meier survival curve was used to assess event-free survival (EFS).ResultsThe high-risk group had a signiifcantly lower number of HGs than the intermediate-risk and low-risk groups (P1.0% (P1.0%组,差异有统计学意义(P<0.05)。结论HGs 可反映B-ALL化疗效果,可用于B-ALL患儿疗效及预后的监测。

  2. Evaluation of mRNA Expression Profile of ABCG2/BCRP in Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    M Entezar-e-Ghaem

    2013-12-01

    Conclusion: Results of this study showed no effect of ABCG2/BCRP expression level on MDR development in ALL. Accordingly, clinical value of ABCG2/BCRP expression profile determination was rejected as the prognosis value for childhood ALL in our geographical area.

  3. ALL-2005方案对儿童急性淋巴细胞白血病髓外白血病防治效果分析%Analysis of prevention and therapeutic effectiveness of extramedullary leukemia in children with childhood acute lymphoblastic leukemia with ALL-2005 protocol

    Institute of Scientific and Technical Information of China (English)

    薛惠良; 顾龙君; 汤静燕; 陈静; 潘慈; 周敏; 董璐; 汤燕静; 王坚敏; 叶启东

    2012-01-01

    目的 总结ALL-2005方案对急性淋巴细胞白血病(ALL)患儿髓外白血病,包括中枢神经系统白血病(CNSL)及睾丸白血病(TL)的防治效果.方法 2005年5月-2008年5月共218例ALL患儿,采用ALL2005方案进行治疗,总结其临床及治疗情况.结果 218例ALL患儿中,5例初诊时伴CNSL,1例于诱导治疗期间发生CNSL,4例于维持治疗期间发生CNSL;1例初诊时伴TL发生,4例维持治疗期间发生TL.经治疗,2例CNSL患儿骨髓复发.其余8例均缓解至今;TL患儿1例骨髓复发,1例放弃治疗,3例缓解至今.结论 ALL2005方案疗效良好,有利于提高患儿长期生存质量.%Objective To analyze the prevention and therapeutic effectiveness of extramedullary leukemia including cen.ral nervous system leukemia ( CNSL) and testicular leukemia (TL) in children with childhood acute lymphoblastic leukemia (ALL) with ALL-2005 protocol. The clinical data were summarized. Methods From May 2005 to May 2008, 218 children with ALL were treated with All-2005 protocol. The clinical data were summarized. Results Five of 218 patients were found with CNSL and 1 with TL at the time of initial diagnosis of ALL, One child developed CNSL during treatment, 4 developed CNSL and 4 developed TL during maintenance treatment. After treatment , 2 patients with CNSL and 1 patient with TL relapsed; and 8 patients with CNSL and 3 patients with TL have been relieved and 1 patient with TL abandoned treatment. Conclusions ALL-2005 protocol shows good therapeutic effectiveness in treatment of children with ALL and improves the life quality of long term survival.

  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. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  6. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  7. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    Science.gov (United States)

    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 from articles published inreputable journals from1994 to date and experiments newly performed by our group, a comprehensive review is written about ABCA2 and its role in MDR regarding childhood ALL. ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. Furthermore, the overexpression ofABCA2 in methotrexate, vinblastine and/or doxorubicin treated Jurkat cells are observed in several publications. The recent study of our group showsthatthe overexpression ofABCA2 gene in children with ALL increases the risk of MDR by 15 times. ABCA2 is the second identified member of the ABCA; ABC transporters' subfamily. ABCA2 gene expression profile is suggested to be an unfavorable prognostic factor in ALL treatment. Better understanding of the MDR mechanisms and the factors involved may improve the therapeutic outcome of ALL by modifying the treatment protocols. PMID:25254091

  8. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance.

    Science.gov (United States)

    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 from articles published inreputable journals from1994 to date and experiments newly performed by our group, a comprehensive review is written about ABCA2 and its role in MDR regarding childhood ALL. ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. Furthermore, the overexpression ofABCA2 in methotrexate, vinblastine and/or doxorubicin treated Jurkat cells are observed in several publications. The recent study of our group showsthatthe overexpression ofABCA2 gene in children with ALL increases the risk of MDR by 15 times. ABCA2 is the second identified member of the ABCA; ABC transporters' subfamily. ABCA2 gene expression profile is suggested to be an unfavorable prognostic factor in ALL treatment. Better understanding of the MDR mechanisms and the factors involved may improve the therapeutic outcome of ALL by modifying the treatment protocols.

  9. The Genomic Landscape of Juvenile Myelomonocytic Leukemia

    Science.gov (United States)

    Chang, Tiffany Y.; Gelston, Laura C.; Wang, Yong-Dong; Mazor, Tali; Esquivel, Emilio; Yu, Ariel; Seepo, Sara; Olsen, Scott; Rosenberg, Mara; Archambeault, Sophie L.; Abusin, Ghada; Beckman, Kyle; Brown, Patrick A.; Briones, Michael; Carcamo, Benjamin; Cooper, Todd; Dahl, Gary V.; Emanuel, Peter D.; Fluchel, Mark N.; Goyal, Rakesh K.; Hayashi, Robert J.; Hitzler, Johann; Hugge, Christopher; Liu, Y. Lucy; Messinger, Yoav H.; Mahoney, Donald H.; Monteleone, Philip; Nemecek, Eneida R.; Roehrs, Philip A.; Schore, Reuven J.; Stine, Kimo C.; Takemoto, Clifford M.; Toretsky, Jeffrey A.; Costello, Joseph F.; Olshen, Adam B.; Stewart, Chip; Li, Yongjin; Ma, Jing; Gerbing, Robert B.; Alonzo, Todd A.; Getz, Gad; Gruber, Tanja; Golub, Todd; Stegmaier, Kimberly; Loh, Mignon L.

    2015-01-01

    Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome. PMID:26457647

  10. [Long-term survival in childhood acute lymphocitic leukemia (author's transl)].

    Science.gov (United States)

    González-Martín, M C; Muñóz Villa, A; García-Miguel, P; Herrero Díez, A; Hurtado Ruano, T; Fernández Epifanio, J L

    1978-01-01

    Long-term results in the treatment of 116 patients of acute lymphocitic leukemia with ages between six months and seven years are reported. A first group A, formed by 76 patients, was treated with prednisone and vincristine as induction protocol and maintenance therapy with 6-mercaptopurine or methotrexate. No neuromeningeal prophylaxis was made, except some cases in which intratecal methotrexate was applied. 27 patients are alive, 21 of them (27,6%) remain in complete remission for more than three years. A second group B, formed by 40 patients, was treated more recently; with an induction protocol composed by prednisone, vincristine and L-asparaginase. All patients in this group received cranial irradiation and intratecal methotrexate. 31 patients are alive (77,5%), 13 of them (32,5%) remain in complete remission for more than two years. The evolution period in this group B is shorter, but some features are exposed which suggest the possibility of long-term better results.

  11. Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Sanna

    2013-01-01

    Full Text Available Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT, and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC regimen plus radiotherapy and donor lymphocyte infusion (DLI. This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

  12. 儿童急性白血病误诊二例原因分析%Cause Analysis of Misdiagnosis and missed Diagnosis of 2 Cases of Childhood Acute Leukemia

    Institute of Scientific and Technical Information of China (English)

    王衍晶; 刘艳; 王贞

    2015-01-01

    目的:探讨儿童急性白血病的临床特点,分析误诊原因并提出防范措施。方法回顾分析我院2012—2013年收治并误诊的儿童急性白血病2例的临床资料。结果本文例1因间断髋关节疼痛1个月、加重并发热5 d就诊,疼痛可自行缓解并反复出现,于外院影像学检查诊断为髋关节滑膜炎,予抗感染治疗无好转,我院门诊按儿童类风湿病(多关节型)予抗风湿治疗,热退疼痛缓解,但仍有多关节活动受限。为系统治疗收入我院儿科,入院后诊断为全身型幼年特发性关节炎,予对症治疗症状缓解,复查血常规发现原始及幼稚细胞,行骨髓血细胞形态检查确诊为急性淋巴细胞白血病。例2因发热、盗汗、乏力6 d,其间伴少量鼻出血3 d 就诊,予退热及抗感染治疗好转,后症状反复出现,入院后按上呼吸道感染予对症治疗无效。复查血常规发现原始细胞,经骨髓血细胞形态检查确诊为急性淋巴细胞白血病。结论对久治不愈的发热、骨痛、感染的患儿要警惕白血病,尽早行骨穿血细胞形态学检查是明确诊断的关键。%Objective To explore the clinical characteristics of childhood acute leukemia, analyzes the causes of mis-diagnosis and missed diagnosis and put forward the preventive measures. Methods Retrospective analysis of clinical data of 2 cases of misdiagnosis and missed diagnosis of childhood acute leukemia admitted during 2012-2013 combined with literature a-nalysis were made. Results Case 1 had intermittent hip pain for 1 month and fever for 5 days. The pain was alleviated by it-self but relapsed. The patient was diagnosed as having synovitis of the hip in the other hospital's imaging and was given anti -inflammatory therapy without any improvement. In our outpatient department, the patient was diagnosed as having childhood rheumatism (multi-joint type) and was given anti - rheumatism treatment. The fever and pain were relieved, but

  13. Population Pharmacokinetics of Ofatumumab in Patients With Chronic Lymphocytic Leukemia, Follicular Lymphoma, and Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Struemper, Herbert; Sale, Mark; Patel, Bela R;

    2014-01-01

    Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma...

  14. Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

    Directory of Open Access Journals (Sweden)

    Anna Mikosik

    Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

  15. Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial.

    Science.gov (United States)

    Wendtner, Clemens M; Hallek, Michael; Fraser, Graeme A M; Michallet, Anne-Sophie; Hillmen, Peter; Dürig, Jan; Kalaycio, Matt; Gribben, John G; Stilgenbauer, Stephan; Buhler, Andreas; Kipps, Thomas J; Purse, Brendan; Zhang, Jennie; De Bedout, Sabine; Mei, Jay; Chanan-Khan, Asher

    2016-01-01

    The objective of this study was to evaluate the safety and efficacy of different lenalidomide starting doses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). CLL patients were randomized to receive lenalidomide at initial doses of 5, 10, or 15 mg/d (N = 103). Doses were escalated by 5 mg every 28-d up to a maximum of 25 mg/d; dose reductions in up to 5 mg decrements were permitted. The most common grade ≥3 adverse events (AEs) were neutropenia and thrombocytopenia. Ten patients died during therapy (four deaths considered as related to lenalidomide); 12 patients experienced second primary malignancies. The most common cause for treatment discontinuation was AEs. Overall response rates were similar across arms. Progression-free survival and overall survival rates were longer in patients who escalated treatment (to 15 or 20 mg/d) versus those who did not. Lower starting doses allowed subsequent dose escalation of lenalidomide while maintaining an acceptable tolerability profile in patients with relapsed/refractory CLL.

  16. Coping Strategies and Locus of Control in Childhood Leukemia: A Multi-Center Research.

    Science.gov (United States)

    Polizzi, Concetta; Fontana, Valentina; Perricone, Giovanna; D'Angelo, Paolo; Jankovic, Momcilo; Taormina, Calogero; Nichelli, Francesca; Burgio, Sofia

    2015-05-25

    Acute lymphoblastic leukemia (ALL) is a very distressing experience for children and requires a special effort of adjustment. Therefore, it seems to be crucial to explore coping resources for the experienced risk condition. In this sense, the study focuses on coping strategies and locus of control in children with ALL during the treatment phase, and on their possible relation. The correlation between children and maternal coping strategies is also investigated. The participants involved were an experimental group of 40 children with ALL and their mothers, and 30 healthy children as the control group. The tools used were: the Child Behavioral Style Scale and the Monitor-Blunter Style Scale to assess the coping strategies of children and mothers; the locus of Control Scale for Children to analyze the children's perception of controlling the events. Both children with ALL and their mothers resorted to monitoring coping strategies with a statistically significant rate of occurrence (children: M=17.8, SD=3.8; mothers: M=10.48, SD=3.4). The data concerning the locus of control show this tendency towards internal causes (M=53.1, SD=4.7). There were statistically significant correlations between monitoring coping strategies and external locus of control (r=0.400, P<0.05). The results gained from the control group are almost equivalent. The outcomes show several interesting resources of the psychological functioning of children as well as of their mothers.

  17. Coping strategies and locus of control in childhood leukemia: a multi-center research

    Directory of Open Access Journals (Sweden)

    Concetta Polizzi

    2015-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a very distressing experience for children and requires a special effort of adjustment. Therefore, it seems to be crucial to explore coping resources for the experienced risk condition. In this sense, the study focuses on coping strategies and locus of control in children with ALL during the treatment phase, and on their possible relation. The correlation between children and maternal coping strategies is also investigated. The participants involved were an experimental group of 40 children with ALL and their mothers, and 30 healthy children as the control group. The tools used were: the Child Behavioral Style Scale and the Monitor-Blunter Style Scale to assess the coping strategies of children and mothers; the locus of Control Scale for Children to analyze the children’s perception of controlling the events. Both children with ALL and their mothers resorted to monitoring coping strategies with a statistically significant rate of occurrence (children: M=17.8, SD=3.8; mothers: M=10.48, SD=3.4. The data concerning the locus of control show this tendency towards internal causes (M=53.1, SD=4.7. There were statistically significant correlations between monitoring coping strategies and external locus of control (r=0.400, P<0.05. The results gained from the control group are almost equivalent. The outcomes show several interesting resources of the psychological functioning of children as well as of their mothers.

  18. 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.

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

    Science.gov (United States)

    2016-10-06

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

  20. MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia

    NARCIS (Netherlands)

    M.M. van den Heuvel-Eibrink (Marry); E.A.C. Wiemer (Erik); M.J. de Boevere; B. van der Holt (Bronno); P.J. Vossebeld (Paula); R. Pieters (Rob); P. Sonneveld (Pieter)

    2001-01-01

    textabstractThe expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, is an independent adverse prognostic factor for response and survival in de novo acute myeloid leukemia (AML). Little is known about MDR1 expression during the development of disease. The pre

  1. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    OpenAIRE

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-s...

  2. 雷利度胺治疗难治复发急性粒细胞白血病临床观察%Clinical Observation of Lenalidomide Treat Relapsed or Refractory Acute Myeloblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    孔德胜; 赵红丽; 董敏; 孙国勋; 施婺丹; 洪珞珈

    2012-01-01

    Objective: To observe toxicities and efficacy in patients relapsed or refractory acute myeloblastic leukemia wit] lenalidomide. Methods: Lenalidomide was given orally at doses of 50mg daily on days 1 through 21 of 28-day cycles. Results: Si Patients were given a median of four prior therapies (range, two to six therapies), frVe patients with AML responded. Two of 6 patient achieved complete remission (CR), two of 6 patients achieved partial remission (PR), one of 6 patients achieved Peripheral bloa improvement,One patient had disease progression death. Toxicities of lenalidomide were Fatigue (4/6), febrile neutropenia (3/6] neutropenia (4/6), thrombocytopenia(l/6), anemia(l/6). Conclusions: Lenalidomide has significant activity in relapsed or refractory acut myeloblastic leukemia patients and the toxicities was active with relatively low toxicity in patients with relapsed/refractory AML.%目的:观察雷利度胺治疗难治复发急性粒细胞白血病的疗效及不良反应.方法:给予雷利度胺单药治疗,雷利度胺50mg/d,口服给药,连续给药21天,28天为一个疗程.结果:应用雷利度胺4(2~6)个疗程,5例有效,2例获得完全缓解,2例部分缓解,1例因疾病迅速进展死亡退出试验.不良反应主要为疲乏4例,中性粒细胞减少性发热3例,中粒细胞减少4例,血小板减少1例,贫血1例.结论:应用雷利度胺治疗难治复发白血病有效,不良反应轻微且易于耐受.

  3. Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Busche, Stephan; Ge, Bing; Vidal, Ramon; Spinella, Jean-François; Saillour, Virginie; Richer, Chantal; Healy, Jasmine; Chen, Shu-Huang; Droit, Arnaud; Sinnett, Daniel; Pastinen, Tomi

    2013-07-15

    B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic determinants underlying disease onset remain unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. Using the Illumina 450K array, we assessed DNA methylation in matched tumor-normal samples of 46 childhood patients with pre-B ALL, extending single CpG-site resolution analysis of the pre-B ALL methylome beyond CpG-islands (CGI). Unsupervised hierarchical clustering of CpG-site neighborhood, gene, or microRNA (miRNA) gene-associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CGIs, CGI shores, and in regions around the transcription start site was found to significantly correlate with transcript expression. Focusing on samples carrying the t(12;21) ETV6-RUNX1 fusion, we identified 119 subtype-specific high-confidence marker CpG-loci. Pathway analyses linked the CpG-loci-associated genes with hematopoiesis and cancer. Further integration with whole-transcriptome data showed the effects of methylation on expression of 17 potential drivers of leukemogenesis. Independent validation of array methylation and sequencing-derived transcript expression with Sequenom Epityper technology and real-time quantitative reverse transcriptase PCR, respectively, indicates more than 80% empirical accuracy of our genome-wide findings. In summary, genome-wide DNA methylation profiling enabled us to separate pre-B ALL according to major subtypes, to map epigenetic biomarkers specific for the t(12;21) subtype, and through a combined methylome and transcriptome approach to identify downstream effects on candidate drivers of leukemogenesis.

  4. Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

    Science.gov (United States)

    2016-07-20

    Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  5. Identification of a novel molecular partner of the E2A gene in childhood leukemia.

    Science.gov (United States)

    Brambillasca, F; Mosna, G; Colombo, M; Rivolta, A; Caslini, C; Minuzzo, M; Giudici, G; Mizzi, L; Biondi, A; Privitera, E

    1999-03-01

    The 'promiscuous' E2A gene, at 19p13.3, is fused with two different molecular partners, PBX1 and HLF, following two chromosome translocations recurrent in childhood pre-B ALL. We have identified a novel gene, FB1, by virtue of its fusion with E2A and by a combination of molecular techniques. FB1 was localized on 19q13.4, suggesting that the novel chimera originated by a cryptic rearrangement of chromosome 19. Two FB1 transcripts, of 1.2 kb and 1.1 kb, are differentially expressed at low level in a variety of human tissues, including hemopoietic cell lines from different lineages. Accordingly, FB1 cDNA displays high homology with a number of cDNA clones from different human tissues. High homology was found also with cDNA clones from mouse and rat, suggesting that the sequence might be conserved at least among mammals. The function of the putative FB1 protein, however, is currently unknown as database sequence comparisons have failed to reveal strong homology with known proteins. The E2A/FB1 fusion appears to be a recurrent feature of pre-B ALLs, suggesting that it might have a role in the development and/or progression of leukemogenesis.

  6. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.

    Science.gov (United States)

    Inaba, Hiroto; Zhou, Yinmei; Abla, Oussama; Adachi, Souichi; Auvrignon, Anne; Beverloo, H Berna; de Bont, Eveline; Chang, Tai-Tsung; Creutzig, Ursula; Dworzak, Michael; Elitzur, Sarah; Fynn, Alcira; Forestier, Erik; Hasle, Henrik; Liang, Der-Cherng; Lee, Vincent; Locatelli, Franco; Masetti, Riccardo; De Moerloose, Barbara; Reinhardt, Dirk; Rodriguez, Laura; Van Roy, Nadine; Shen, Shuhong; Taga, Takashi; Tomizawa, Daisuke; Yeoh, Allen E J; Zimmermann, Martin; Raimondi, Susana C

    2015-09-24

    Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% ± 2.7% and 49.0% ± 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9;11)(p22;q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.

  7. Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL

    Directory of Open Access Journals (Sweden)

    Greg Hodge

    2008-03-01

    Full Text Available Greg Hodge1, Stephen Davis2, Michael Rice1, Heather Tapp1, Ben Saxon1, Tamas Revesz11Haematology/Oncology Department, Women’s and Children’s Hospital, North Adelaide, Australia; 2Department of Mycology, Women’s and Children’s Hospital, North Adelaide, AustraliaAbstract: Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferonγ, interleukin-2 or tumor necrosis factor-α intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.Keywords: childhood precursor-B acute lymphoblastic leukemia, garlic, apoptosis, immune function, intracellular cytokines

  8. Role of Electromagnetic Field Exposure in Childhood Acute Lymphoblastic Leukemia and No Impact of Urinary Alpha- Amylase--a Case Control Study in Tehran, Iran.

    Science.gov (United States)

    Tabrizi, Maral Mazloomi; Hosseini, Seyed Ahmad

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies which accounts for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring. This study aimed to evaluate the influence of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL. It also examines the role of various factors such as environmental factors and alpha-amylase as a marker in the development of leukemia. This cross-sectional case control study was carried out on 22 cases and 100 controls who born and lived in low socioeconomic families in Tehran and were hospitalized for therapeutic purposes in different hospitals of rom 2013-2014. With regard to the underlying risk factors; familial history and parental factors were detected as risk factors of ALL but in this age, socioeconomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factor (p=0.006, OR=3.651, CI 95% 1.692-7.878). As the population study was from low socioeconomic state, use of mobiles, computers and microwaves was negligible. Moreover prenatal and postnatal exposure to all indoor electrically charged objects were not detected as significant environmental factors in the present study. This work defined the risk of environmental especially continuous pre and postnatal exposure to high voltage power lines and living in pollutant regions through the parents or children as well as the previously described risk factors of ALL for the first time in low socioeconomic status Iranian population.

  9. Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.

    Science.gov (United States)

    Chiou, Shyh-Shin; Wang, Li-Ting; Huang, Shih-Bo; Chai, Chee-Yin; Wang, Shen-Nien; Liao, Yu-Mei; Lin, Pei-Chin; Liu, Kwei-Yan; Hsu, Shih-Hsien

    2014-10-01

    B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.

  10. Vorinostat and Decitabine in Treating Patients With Relapsed, Refractory, or Poor-Prognosis Hematologic Cancer or Other Diseases

    Science.gov (United States)

    2013-01-04

    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); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  11. Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells

    Directory of Open Access Journals (Sweden)

    Yun-Ju Chen

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein’s beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.

  12. Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

    Directory of Open Access Journals (Sweden)

    Madzo Jozef

    2005-04-01

    Full Text Available Abstract Background Aberrant expression of myeloid antigens (MyAgs on acute lymphoblastic leukemia (ALL cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases. Methods In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. Results We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p Conclusion In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

  13. Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia

    Directory of Open Access Journals (Sweden)

    Widjajanto PH

    2013-02-01

    Full Text Available Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL, especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58 and to the placebo arm (n = 52. Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8% achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884 versus 270 (range: 14–25,480 × 109 cells/L (P > 0.01, greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07, clinical sepsis (50.0% versus 38.5%, P = 0.22, and death (18.9% versus 5.8%, P = 0.05.Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

  14. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

    Science.gov (United States)

    Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Kohji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata-Kawata, Hiroko; Sakamoto, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Tsuyoshi; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

    2017-01-01

    Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. PMID:27634205

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

    DEFF Research Database (Denmark)

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

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

  16. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

    Science.gov (United States)

    Eapen, M; Zhang, M-J; Devidas, M; Raetz, E; Barredo, J C; Ritchey, A K; Godder, K; Grupp, S; Lewis, V A; Malloy, K; Carroll, W L; Davies, S M; Camitta, B M

    2008-02-01

    In children with acute lymphoblastic leukemia (ALL) with isolated central nervous system (CNS) relapse and a human leucocyte antigen (HLA)-matched sibling, the optimal treatment after attaining second remission is unknown. We compared outcomes in 149 patients enrolled on chemotherapy trials and 60 HLA-matched sibling transplants, treated in 1990-2000. All patients achieved a second complete remission. Groups were similar, except the chemotherapy recipients were younger at diagnosis, less likely to have T-cell ALL and had longer duration (> or = 18 months) first remission. To adjust for time-to-transplant bias, left-truncated Cox's regression models were constructed. Relapse rates were similar after chemotherapy and transplantation. In both treatment groups, relapse rates were higher in older children (11-17 years; RR 2.81, P=0.002) and shorter first remission (< 18 months; RR 3.89, P<0.001). Treatment-related mortality rates were higher after transplantation (RR 4.28, P=0.001). The 8-year probabilities of leukemia-free survival adjusted for age and duration of first remission were similar after chemotherapy with irradiation and transplantation (66 and 58%, respectively). In the absence of an advantage for one treatment option over another, the data support use of either intensive chemotherapy with irradiation or HLA-matched sibling transplantation with total body irradiation containing conditioning regimen for children with ALL in second remission after an isolated CNS relapse.

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

    Science.gov (United States)

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  18. Using a Bayesian hierarchical model for identifying single nucleotide polymorphisms associated with childhood acute lymphoblastic leukemia risk in case-parent triads.

    Directory of Open Access Journals (Sweden)

    Ying Cao

    Full Text Available Childhood acute lymphoblastic leukemia (ALL is a condition that arises from complex etiologies. The absence of consistent environmental risk factors and the presence of modest familial associations suggest ALL is a complex trait with an underlying genetic component. The identification of genetic factors associated with disease is complicated by complex genetic covariance structures and multiple testing issues. Both issues can be resolved with appropriate Bayesian variable selection methods. The present study was undertaken to extend our hierarchical Bayesian model for case-parent triads to incorporate single nucleotide polymorphisms (SNPs and incorporate the biological grouping of SNPs within genes. Based on previous evidence that genetic variation in the folate metabolic pathway influences ALL risk, we evaluated 128 tagging SNPs in 16 folate metabolic genes among 118 ALL case-parent triads recruited from the Texas Children's Cancer Center (Houston, TX between 2003 and 2010. We used stochastic search gene suggestion (SSGS in hierarchical Bayesian models to evaluate the association between folate metabolic SNPs and ALL. Using Bayes factors among these variants in childhood ALL case-parent triads, two SNPs were identified with a Bayes factor greater than 1. There was evidence that the minor alleles of NOS3 rs3918186 (OR = 2.16; 95% CI: 1.51-3.15 and SLC19A1 rs1051266 (OR = 2.07; 95% CI: 1.25-3.46 were positively associated with childhood ALL. Our findings are suggestive of the role of inherited genetic variation in the folate metabolic pathway on childhood ALL risk, and they also suggest the utility of Bayesian variable selection methods in the context of case-parent triads for evaluating the role of SNPs on disease risk.

  19. What Is Childhood Leukemia?

    Science.gov (United States)

    ... Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, Answers, and Hope. Available Every Minute ... 227.2345 Live Chat Follow Us Twitter Facebook Instagram help site map privacy accessibility terms of use ...

  20. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  1. Space-Time Clustering of Childhood Leukemia: Evidence of an Association with ETV6-RUNX1 (TEL-AML1) Fusion

    Science.gov (United States)

    Lupatsch, Judith E.; Niggli, Felix; Egger, Matthias; Kuehni, Claudia E.; Spycher, Ben D.

    2017-01-01

    Background Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters. Methods We identified cases of persons born and diagnosed between 1985 and 2014 at age 0–15 years from the Swiss Childhood Cancer Registry. We determined spatial and temporal lags that maximized evidence of clustering based on the Knox test and classified cases born within these lags from another case as clustered. Using logistic regression adjusted for child population density, we determined whether clustering status was associated with age at diagnosis, immunophenotype, cytogenetic subtype, perinatal and socioeconomic characteristics, and pollution sources. Results Analyses included 1,282 cases of which 242 were clustered (born within 1 km and 2 years from another case). Of all investigated characteristics only the t(12;21)(p13;q22) translocation (resulting in ETV6-RUNX1 fusion) differed significantly in prevalence between clustered and nonclustered cases (40% and 25%, respectively; adjusted OR 2.54 [1.52–4.23]; p = 0.003). Spatio-temporal clustering was driven by an excess of aggregations of two or three children rather than by a few large clusters. Conclusion Our findings suggest ETV6-RUNX1 is associated with space-time clustering of CL and are consistent with an infection interacting with that oncogene in early life leading to clinical leukemia. PMID:28129329

  2. Flow cytometric analysis of peripheral blood leukemic cells in relapse of acute leukemia%急性白血病复发外周血白血病细胞的流式细胞术检验分析

    Institute of Scientific and Technical Information of China (English)

    杨莉; 何浩明

    2015-01-01

    Objective To analyse status of peripheral blood leukemic cells detected by flow cytometry in patients with acute leu‐kemia(AL) ,and to provide references for evaluating clinical efficacy and prognosis of AL .Methods The peripheral blood specimens of 87 cases of patients with AL ,including 53 cases of patients with acute myelocytic leukemia and 34 cases of patients with acute lymphoblastic leukemia ,were detected by using flow cytometry ,morphological changes in bone marrow cells were detected ,as well . Results The sensitivity ,specificity and positive predictive value in determination of acute myelocytic leukemia was 95 .6% ,34 .5%and 81 .3% respectively ,and those in acute lymphoblastic leukemia was 87 .3% ,45 .6% and 68 .9% respectively ,statistically signif‐icant differences were found in sensitivity ,specificity and positive predictive value (P<0 .05) .A total of 19 cases with negative mini‐mal residual disease had recurrence(26 .31% ) after 24 months ,and 68 cases with positive minimal residual disease had recurrence (86 .76% ) after 24 months ,and the recurrence rate between the two groups was statistically significant (P<0 .05) .Among all pa‐tients with positive minimal residual disease ,the recurrence rate in patients with high expression level of minimal residual disease (88 .23% ) was higher than that in patients with low expression level of minimal residual disease (47 .09% ) ,and the difference was statistically significant (P<0 .05) .Conclusion Flow cytometric analysis of peripheral blood leukemic cells may has significance for diagnosing relapse of AL and guiding clinical medication .%目的:分析急性白血病(AL)患者外周血白血病细胞流式细胞术检测情况,为分析AL的临床疗效和预后提供参考。方法采用流式细胞术检测87例A L患者(急性髓细胞白血病53例、急性淋巴细胞白血病34例)外周血标本,同时检测骨髓细胞形态学变化。结果急性髓细胞白

  3. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

    Directory of Open Access Journals (Sweden)

    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  4. Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1.

    Science.gov (United States)

    Purizaca, Jessica; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Vadillo, Eduardo; Arriaga-Pizano, Lourdes; Fuentes-Figueroa, Silvestre; Villagomez-Barragán, Horacio; Flores-Guzmán, Patricia; Alvarado-Moreno, Antonio; Mayani, Hector; Meza, Isaura; Hernandez, Rosaura; Huerta-Yepez, Sara; Pelayo, Rosana

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34⁺ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  5. Factors predicting the risk of seizure relapse after antiepilepsy drug withdrawal in childhood epilepsy%癫(痫)患儿撤药后复发的相关因素

    Institute of Scientific and Technical Information of China (English)

    胡文静; 廖红梅; 唐静文; 方红军; 杨赛; 陈玫

    2014-01-01

    Objective To investigate the factors associated with seizure relapse after antiepilepsy drug (AED) withdrawal in childhood epilepsy.Methods A retrospective analysis was conducted in epileptic children of Hunan Children's Hospital from Jan.2003 to Jan.2011.Among those with anti-epileptic therapy for seizure-free period over 2 years,the patients who relapsed after withdrawal were followed up through outpatient clinic visits and/or by telephone interviews for at least 2 years.Results Of the 127 cases of children enrolled in this study,28 patients(22.05%) relapsed [male:12/59 cases (20.34%) and female:16/68 cases (23.53%)].Cumulative relapse rates were 18.18% (8/44 cases) in infancy,15.79% (6/38 cases) in toddlers,23.53% (8/34 cases) in preschool children,and 54.55% (6/11 cases)in school age group.Of the patients who relapsed,generalized seizure occurred in 12/87 cases (13.79%),partial seizure in 16/40 cases(40.00%).According to seizure frequency between the first seizure and AED administration,3 cases(6.25%) relapsed among 48 cases of seizure frequency < 5 times,13 cases(24.07%) relapsed among 54 cases of seizure frequency 5 to 10 times,and 12 cases(48.00%) relapsed among 25 cases of seizure frequency more than 10 times.Relapse occurred in 9 cases of monotherapy(9/91 cases,9.89%) and in 19 cases of polytherapy (19/36 cases,52.78%).According to the seizure control period (period between the beginning of antiepileptic treatment and AED withdrawal),14 cases relapsed among 37 cases with the seizure control period of 2 to 3 years (37.84%),8 cases relapsed among 51 cases with the period of 3 to 4 years (15.69%),and 6 cases relapsed among 39 cases with the period of 4 to 5 years(15.38%).According to AED tapering off period,10 cases relapsed among 24 cases with the period of 3 months (41.67%),9 cases relapsed among 36 cases with the period of 3-6 mc ths (25.00%),and 9 cases relapsed among 67 cases with the period of over 6 months(13.43

  6. NKAML: A Pilot Study to Determine the Safety and Feasibility of Haploidentical Natural Killer Cell Transplantation in Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Inaba, Hiroto; Ribeiro, Raul C.; Pounds, Stanley; Rooney, Barbara; Bell, Teresa; Pui, Ching-Hon; Leung, Wing

    2010-01-01

    Purpose To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). Patients and Methods Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day −7) and fludarabine (25 mg/m2/d on days −6 through −2), followed by killer immunoglobulin-like receptor–human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 × 106/kg NK cells) and six doses of interleukin-2 (1 million U/m2). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). Conclusion Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML. PMID:20085940

  7. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  8. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2010-01-01

    BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health...

  9. 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.

  10. Approaches for cytogenetic and molecular analyses of small flow-sorted cell populations from childhood leukemia bone marrow samples

    DEFF Research Database (Denmark)

    Obro, Nina Friesgaard; Madsen, Hans O.; Ryder, Lars Peter;

    2011-01-01

    defined cell populations with subsequent analyses of leukemia-associated cytogenetic and molecular marker. The approaches described here optimize the use of the same tube of unfixed, antibody-stained BM cells for flow-sorting of small cell populations and subsequent exploratory FISH and PCR-based analyses....

  11. 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

  12. 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

  13. 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

  14. Physical Activity in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: A Cross-sectional Cohort Study.

    Science.gov (United States)

    Nayiager, Trishana; Barr, Ronald D; Anderson, Loretta; Cranston, Amy; Hay, John

    2017-01-01

    Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium. The median age was 21.15 years and time from diagnosis 15.07 years, and 27 subjects had experienced fractures. More than 30% of the total sample were OW/OB. There was no correlation of body mass index with present PA. There were no significant differences between those with/without fractures in terms of age, sex, time from diagnosis, and the prevalence of OW/OB. Subjects with fractures during treatment reported more total activity on typical weekend days than those without fractures (mean 8.8 vs. 6.9 h, P<0.01). There was no significant difference on weekdays. Higher activity on weekends suggests that fractures may have occurred more commonly in those who had a more active lifestyle before, during, and after treatment.

  15. Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: A population-based case-control study in the five Nordic countries

    Energy Technology Data Exchange (ETDEWEB)

    Svahn-Tapper, Gudrun [Univ. Hospital, Lund (Sweden). Dept. of Radiation Physics

    2006-06-15

    The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960-1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

  16. Down syndrome preleukemia and leukemia.

    Science.gov (United States)

    Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

    2015-02-01

    Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need.

  17. Applying molecular epidemiology in pediatric leukemia.

    Science.gov (United States)

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

  18. Vitamin D and bone minerals status in the long-term survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2015-01-01

    Conclusions: ALL treatment is associated with the increase in prevalence of vitamin D insufficiency in the childhood ALL survivors and since the low vitamin D level potentially increases the risk of low bone density, subsequent malignancies, and cardiovascular disease in the survivors, close follow-up of such patients are highly recommended to prevent the stated complications.

  19. CD+4 Foxp3+调节性T淋巴细胞在儿童急性白血病中的表达及其与微小残留病的关系%The level of CD+4 Foxp3+ regulatory T cells in patients with childhood acute leukemia and its relationship with the minimal residual disease of leukemia

    Institute of Scientific and Technical Information of China (English)

    徐翀; 关明; 蒋黎敏; 江华; 孙婴

    2009-01-01

    Objective To study the regulatory T cells (Treg-cell) frequencies in patients with childhood acute leukemia and evaluate its clinical application value by investigating the relationship between the increasing numbers of Treg cells and minimal residual disease of leukemia (MRD), Methods Foxp3-FITC/CD25-PE/CD4-PerCP/CD3-APC four-color staining flow cytometry was established to identify Treg cells. Treg cells frequencies both in 10 healthy controls and in 33 patients with newly diagnosed childhood acute leukemia ( B-ALL 17 cases, T-ALL 9 cases, AML 7 cases) were detected. The possibility of the accumulation of Treg cells being the prognostic marker for acute leukemia was evaluated by comparing the results of Treg cells frequency with that of MRD. Results The percentage of Treg cells in CD+4 CD+3 T cells was M = 8. 09% in normal bone marrows, which was significantly different from the results in the bone marrows of newly diagnosed childhood acute leukemia ( M = 12.77% , U = 3.41, P 0.05).Treg数量与临床病理学参数无显著相关性.此外,Treg数量在MRD阳性组(M=14.74%)与MRD持续阴性组(M=11.3%)中的差异有统计学意义(t=252.5,P<0.05).结论 白血病初发患儿体内的Treg数量显著增高,且患儿中Treg表达水平与MRD有关联.高水平Treg预示白血病患儿预后较差,存在复发的可能.

  20. Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.

    Science.gov (United States)

    Takenaka, Katsuto; Nishida, Tetsuya; Asano-Mori, Yuki; Oshima, Kumi; Ohashi, Kazuteru; Mori, Takehiko; Kanamori, Heiwa; Miyamura, Koichi; Kato, Chiaki; Kobayashi, Naoki; Uchida, Naoyuki; Nakamae, Hirohisa; Ichinohe, Tatsuo; Morishima, Yasuo; Suzuki, Ritsuro; Yamaguchi, Takuhiro; Fukuda, Takahiro

    2015-11-01

    Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911), chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n = 569) who underwent their first allo-HSCT from HLA-matched related or unrelated donors between 2000 and 2009 and who survived without disease relapse until day 100 after transplantation were analyzed. Patients who received umbilical cord blood transplantation were not included. Patients underwent surveillance by pp65 antigenemia from the time of engraftment, and the beginning of preemptive therapy was defined as CMV reactivation. Cox proportional hazards models were used to evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as time-dependent covariates. CMV reactivation was associated with a decreased incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%) relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV developed in 630 patients (34.3%). By multivariate analysis considering competing risk factors, 3

  1. Renal Presentation in Pediatric Acute Leukemia: Report of 2 Cases.

    Science.gov (United States)

    Sherief, Laila M; Azab, Seham F; Zakaria, Marwa M; Kamal, Naglaa M; Abd Elbasset Aly, Maha; Ali, Adel; Abd Alhady, Mohamed

    2015-09-01

    Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11 × 10⁹/L, hemoglobin 8.7 g/dL and platelet count 197 × 10⁹/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup.

  2. Living near overhead high voltage transmission power lines as a risk factor for childhood acute lymphoblastic leukemia: a case-control study.

    Science.gov (United States)

    Sohrabi, Mohammad-Reza; Tarjoman, Termeh; Abadi, Alireza; Yavari, Parvin

    2010-01-01

    This study aimed to investigate association of living near high voltage power lines with occurrence of childhood acute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmed ALL were selected from all referral teaching centers for cancer. They interviewed for history of living near overhead high voltage power lines during at least past two years and compared with 300 controls which were individually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were used for analysis when appropriate. The case group were living significantly closer to power lines (Plines (Plines against more than 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for 230 KV and 2.98 (95%CI: 0.93 to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters from the nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.

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

    Energy Technology Data Exchange (ETDEWEB)

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

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

  4. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  5. 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

  6. Relapsing polychondritis

    Directory of Open Access Journals (Sweden)

    Lincoln Sakiara Miyasaka

    Full Text Available PURPOSE: This article describes a clinically-diagnosed case of relapsing polychondritis (RP, attended at the Hospital São Paulo, and presents a literature review of the subject. SOURCE OF RESEARCH: The literature review was made via Medline (1990-96, Lilacs (1980-96, textbooks of rheumatology, and some articles about the history of the disease. In Medline, 113 articles from 1990 to 1996 were found, and there were 23 articles from 1980 to 1996 in Lilacs. RESEARCH PROCEDURE: We reviewed the articles available at BIREME (Biblioteca Regional de Medicina with the primary focus being on the disease in question. SUMMARY: RP is a rare disease of unknown etiology described initially by Jackson-Wartenhorst in 1923 and characterized by a recurrent and acute inflammatory process that causes the collapse of the cartilaginous structures and their subsequent replacement by fibrous connective tissue. The cartilage most commonly attacked is that of the auricle of the ear and nasal septum, while the cartilage of the trachea, larynx, epiglottis, ribs, and articulations may also be involved. Ocular inflammations and systemic reactions with fever are also described. In 1976, McAdam presented a complete prospective study of 23 patients, reviewed the 136 cases described up until that time, and then proposed diagnostic criteria which were later expanded by Damiani and Levine. Currently, more than 500 cases have been described. CONCLUSION: Although a rare disease, better knowledge of it is needed, as RP may be lethal with tracheal collapse and obstruction of respiratory pathways, making precise diagnosis and adequate therapeutic intervention necessary.

  7. 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...... TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6....../27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower...

  8. MRI diagnosis of bone marrow relapse in children with ALL

    Energy Technology Data Exchange (ETDEWEB)

    Kan, J.H.; Hernanz-Schulman, Marta [Vanderbilt University, Department of Radiology and Radiological Sciences, Vanderbilt Children' s Hospital, Nashville, TN (United States); Frangoul, Haydar A. [Vanderbilt University, Department of Pediatric Hematology-Oncology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Connolly, Susan A. [Harvard Medical School, Department of Radiology, Boston Children' s Hospital, Boston, MA (United States)

    2008-01-15

    Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

  9. Relapsing polychondritis in childhood: report of three cases and review of the literature%儿童复发性多软骨炎三例及文献复习

    Institute of Scientific and Technical Information of China (English)

    肖娟; 刘文君; 宋红梅; 魏珉; 尤欣; 姜英

    2009-01-01

    Objective To analyze the clinical features, diagnosis, treatment and prognosis of relapsing polychondritis (RP) in childhood. Methods A retrospective analysis of three cases of childhood RP from our hospital on clinical features, diagnosis and treatment was performed, data of the other sixteen cases from MEDLINE were also reviewed. Clinical features of all nineteen children with RP were compared with adults with RP. Results The age of the three cases at the time of diagnosis ranged from 10 years to 15 years (the minimum age was 2 years in the literature). The course from onset of clinical symptom to making definite diagnosis varied from 3 months to 9 months (from 3 months to 2 years in the literature). In the three cases, childhood RP affected multiple system/organs, and produced diverse clinical manifestations such as arthritis, auricular chondritis, nasal chondritis (leading to a saddle nose deformity), conjunctivitis and so on. Also, tracheostomy was performed because of severe difficulty in breathing for all the 3 cases. Compared with adult RP, involvement of respiratory system existed in 78.9% of childhood patients, which was more frequent and serious than that of adult cases with RP (35.2%); arthritis was the most common clinical manifestation and first symptoms; Fewer children with RP were associated with other autoimmune diseases than adults. Although both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) blood levels were high in the three cases, anti-nuclear antibody (ANA), double stranded DNA (dsDNA) and extractable nuclear antigen (ENA) were all negative, it was difficult to define the diagnosis of RP because there were no specific laboratory indicators for diagnosis. The confirmation of diagnosis of two cases was relied on clinical criteria, while another case got pathological material for diagnostic support. CT images with three-dimensional reconstruction of the respiratory tract were helpful for early diagnosis of childhood RP. All

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

    Science.gov (United States)

    2016-04-21

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  12. Prognostic Impact of Absolute Lymphocyte Counts at the End of Remission Induction in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Campbell, Patrick; Zhou, Yinmei; Sandlund, John T.; Jeha, Sima; Ribeiro, Raul C.; Inaba, Hiroto; Bhojwani, Deepa; Relling, Mary V.; Howard, Scott C.; Campana, Dario; Pui, Ching-Hon

    2013-01-01

    Background Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. Methods Outcomes of 399 patients ≤ 18 years of age with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children’s Research Hospital were analyzed according to ALC at the end of remission induction therapy. Results ALC ≥ 500 cell/μL was significantly more prevalent among patients with B-lineage ALL, favorable presenting features and in those who achieved minimal residual disease (MRD) negativity on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD at the end of induction (p > 0.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS of 84.2% ± 8.9% versus 97.3 ± 1.0 for patients with higher ALC (P = .036). Conclusion ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided, therapy. PMID:23456849

  13. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.

    Science.gov (United States)

    Balgobind, Brian V; Raimondi, Susana C; Harbott, Jochen; Zimmermann, Martin; Alonzo, Todd A; Auvrignon, Anne; Beverloo, H Berna; Chang, Myron; Creutzig, Ursula; Dworzak, Michael N; Forestier, Erik; Gibson, Brenda; Hasle, Henrik; Harrison, Christine J; Heerema, Nyla A; Kaspers, Gertjan J L; Leszl, Anna; Litvinko, Nathalia; Nigro, Luca Lo; Morimoto, Akira; Perot, Christine; Pieters, Rob; Reinhardt, Dirk; Rubnitz, Jeffrey E; Smith, Franklin O; Stary, Jan; Stasevich, Irina; Strehl, Sabine; Taga, Takashi; Tomizawa, Daisuke; Webb, David; Zemanova, Zuzana; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M

    2009-09-17

    Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.

  14. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  15. Acute myelogenous leukemia and acute leukemic appendicitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Po-Jen Hsiao; Shih-Ming Kuo; Jia-Hong Chen; Hsuen-Fu Lin; Pau-Ling Chu; Shih-Hua Lin; Ching-Liang Ho

    2009-01-01

    Acute myelogenous leukemia (AML) can involve the gastrointestinal tract but rarely involves the appendix.We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leukemia relapse. Pathological findings of the appendix revealed transmural infiltrates of myeloblasts, whichindicated a diagnosis of leukemia. Unfortunately, the patient died from progression of the disease on the 19th d after admission. Although leukemic cell infiltration of the appendix is uncommon, patients with leukemia relapse can present with symptoms mimicking acute appendicitis.

  16. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2016-06-17

    B-Cell Prolymphocytic Leukemia; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  17. Progress of Studies on Genetics of Childhood Acute Leukemia——Review%儿童急性白血病遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    岳志霞; 郑胡镛

    2013-01-01

    This study on determination of leukemia-specific chromosomal abnormalities and their relationship with prognosis of childhood acute leukemia(AL) had an important significance for childhood acute leukemia.In recent years,the efficacy of treatment of childhood AL has been greatly improved,but relapse is still a main factor affecting prognosis.Treatment based on the risk stratification by cytogenetic abnormalities can improve the prognosis and survival rate.In the past 3 decades,the genetic techniques have developed rapidly and many new genetic abnormalities have been found.This review highlights the main chromosomal and genomic abnormalities of 3 common childhood AL,including B-cell precursor acute lymphoblastic leukemia(BCP-ALL),T-cell acute lymphoblastic leukemia(T-ALL) and acute myeloid leukemia(AML).%白血病特异染色体异常的确定及其与预后关系的研究对儿童急性白血病(acute leukemia,AL)具有极其重要的意义.近年来,虽然儿童AL的治疗效果有了很大改善,但其复发仍然是影响预后的主要因素.根据遗传学异常进行危险度分层,并指导治疗,可以改善儿童AL预后,提高患儿生存率.在过去的30年中,遗传学检测技术有了突飞猛进的发展,发现了许多新的遗传学异常.本文就三种儿童常见AL,包括前B细胞急性淋巴细胞白血病(B-cell precursor acute lymphoblastic leukemia,BCP-ALL)、T细胞急性淋巴细胞白血病(T-cell acute lymphoblastic leukemia,T-ALL)和急性髓系白血病(acute myeloid leukemia,AML)的最新遗传学研究进展进行综述.

  18. Incidence of childhood leukemia around French nuclear sites between 1990 and 1998;Incidence des leucemies de l'enfant aux alentours des sites nucleaires francais entre 1990 et 1998

    Energy Technology Data Exchange (ETDEWEB)

    White-Koning, M.; Hemon, D.; Goubin, A.; Clavel, J. [Inserm-U754, 94 - Villejuif (France); Laurier, D.; Tirmarche, M. [Institut de Radioprotection et de Surete Nucleaire, 92 - Fontenay aux Roses (France); Jougla, E. [Institut National de la Sante et de la Recherche Mrdicale Inserm-CepiDc, 78 - Le Vesinet (France)

    2006-01-15

    The works presented here constitute the first systematic study of the incidence of childhood leukemia around the whole of French nuclear facilities. Globally, the incidence of childhood leukemia does not diverge significantly of the expected incidence during the period 1990-1998. It does not show a decrease of S.I.R. (standardized incidence ratio) in function of the distance from child's home to the nuclear site whatever be the age. This study represents the first analysis of the incidence of leukemia focusing on 29 French nuclear sites, including the whole of the 19 C.N.P.E. ( nuclear power plants that produce electric power), and is based on incidence data rather than mortality. The period, the age groups and the studied area have been all chosen a priori, that gives a statistical validity to the results. The estimation of population at risk have been made with several different methods of interpolation in order to check the stability of estimations. The different methods of statistical analysis used have lead to extremely close results, reinforcing our confidence in the reliability of our estimations. The excess of leukemia incidence observed at Chinon and Civaux and the deficit observed at Bruyere/Saclay/Fontenay loose their statistical significance when the correction of Bonferroni is applied. So, the global analysis of the 29 sites and the analysis by site have not shown statistically significant difference between the numbers of observed and expected cases. The study of the 19 C.N.P.E. gave same results, even in taken into account their electric power or their year of service. The possibility of confounding factors has been excluded. The power of the study to detect excess incidence and a decrease of S.I.R. with distance from the site was examined under different alternative hypotheses through simulation methods. For values of S.I.R. near the site (0-5 km) between 1.5 and 2 and a risk of error of 5%, the power of the study is between 96% and 100

  19. Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

    Science.gov (United States)

    2016-06-02

    Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

  20. Evaluation of rs62527607 [GT] single nucleotide polymorphism located in BAALC gene in children with acute leukemia using mismatch PCR-RFLP.

    Science.gov (United States)

    Nadimi, Motahareh; Rahgozar, Soheila; Moafi, Alireza; Tavassoli, Manoochehr; Mesrian Tanha, Hamzeh

    2016-01-01

    Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL.

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

    Science.gov (United States)

    2016-07-08

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

  2. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute ... bleeding and forming blood clots. Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk ...

  3. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Science.gov (United States)

    Rudant, Jérémie; Orsi, Laurent; Bonaventure, Audrey; Goujon-Bellec, Stéphanie; Baruchel, André; Petit, Arnaud; Bertrand, Yves; Nelken, Brigitte; Pasquet, Marlène; Michel, Gérard; Saumet, Laure; Chastagner, Pascal; Ducassou, Stéphane; Réguerre, Yves; Hémon, Denis; Clavel, Jacqueline

    2015-01-01

    Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non

  4. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis.

    Directory of Open Access Journals (Sweden)

    Orsolya Lautner-Csorba

    Full Text Available In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52×10(-4; OR = 2.00. The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21×10(-3; OR = 0.55, which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01. The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful

  5. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  6. The effects of donor peripheral blood stem cell infusion in the prevention of relapse in high risk leukemia after haplotype hematopoietic stem cell transplantation%供者外周血干细胞输注预防高危白血病单倍型移植后复发的临床研究

    Institute of Scientific and Technical Information of China (English)

    张媛; 陈惠仁; 刘晓东; 何学鹏; 楼金星; 郭智

    2011-01-01

    目的 探讨供者粒细胞集落刺激因子(G-CSF)动员外周血干细胞输注对高危复发白血病患者单倍型移植后白血病复发的预防作用,评价其疗效及安全性.方法 对20例复发未缓解白血病患者在单倍型造血十细胞移植(HSCT)后给予预防性外周血干细胞输注,供者接受G.CSF 5~10μg·kg-1·d-1,分次注射,第5天采集外周血干细胞,在移植90 d后(+90 d)行第1次输注,30 d后4例患者行第2次输注,除1例第1次输注的单个核细胞数(MNC)为0.1×108个/kg外,其他患者均为0.2×108个/kg.外周血千细胞输注后观察移植物抗宿主病(GVHD)的发生、白血病复发率及患者长期生存的情况.结果 外周血干细胞输注后,中位随访25(4~印)个月,19例患者发生急性GVHD,其中Ⅲ度以上4例,累积发生率22.9%,均是接受2次输注的患者;可以评价的慢性GVHD13例,其中10例为局限性慢性GVHD.无患者因GVHD死亡.9例患者复发死亡,其余11例患者无病生存,其中4例慢性髓性白细胞、4例急性髓性白细胞(AML)、1例淋巴瘤性白血病、2例骨髓增生异常综合征转AML,Kaplan-Meier生存计算2年无病生存率为52.5%.结论 G-CSF动员外周血干细胞输注预防单倍型HSCT后白血病复发,效果显著,安全性较好.%Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long

  7. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    DEFF Research Database (Denmark)

    Bruedigam, Claudia; Bagger, Frederik O; Heidel, Florian H;

    2014-01-01

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key...

  8. Residential pesticides and childhood leukemia: a systematic review and meta-analysis Pesticidas residenciais e leucemia na infância: revisão sistemática e meta-análise

    Directory of Open Access Journals (Sweden)

    Michelle C. Turner

    2011-03-01

    Full Text Available It is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood and childhood leukemia. Searches of Medline and other electronic databases were performed (1950-2009. Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs and 95% confidence intervals (Cis. Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.Trata-se de uma revisão sistemática e meta-análise de estudos epidemiológicos observacionais anteriores que examinaram a relação entre a exposição de pesticidas residenciais durante as janelas de exposição crítica do tempo (pré-concepção, gravidez e infância e leucemia infantil. Foram realizadas pesquisas de dados em diversas bases de dados eletrônicas como Medline e outras. Dois revisores independentes realizaram o estudo de seleção, abstração de dados e avaliação da qualidade. Foram utilizados modelos de efeitos aleatórios para obtenção de razões chances (odds ratio e intervalos de confiança de 95% (IC. Dos 17 estudos identificados, 15 foram incluídos na meta

  9. 短程大剂量米托蒽醌和阿糖胞苷治疗难治性和复发的急性白血病(英文)%Short Coures high Dose Mitoxantrone with Cytarabine for Treatment of Refractory and Relapsed Acute Leukemia

    Institute of Scientific and Technical Information of China (English)

    王恒湘

    2001-01-01

    Although chemotherapy can achieve a high rate of disease remission in patients with newly diagnosed acute leukemia, patients with recurrent or refractory leukemia generally have a poorer rate of response. This study was designed to assess the utility of high-dose mitoxantrone and intermediate-dose cytarabine in the treatment of patients with relapsed or refractory acute leukemia. Thirty patients with relapsed or refractory acute lenkemia were treated with mitoxantrone at a total dose of 40 mg/m2 intravenously and cytarabine 1 - 1.5 g/m2 over 3 hours once daily for five doses. Twenty-six of thirty patients achieved complete response (CR 87%) and one achieved partial response (PR 3.3%). No patient died during the induction course. The main toxxic effect was hematopoietic suppwession that was clinically acceptable. The median time needed for CR was around 30 days. The median disease-free and overall survival times were 3.5 and 6 months, respectively. The results demonstrate that shshort course high-dose mitoxantrone with cytarabine is associated with a trend toward a higher CR rate and therefore, it should be an effective antileukemic regimen for the treatment of refractory and relapsed acute leukemia.%初诊的急性白血病,化疗常可获得较高的缓解率,而难治性和复发的白血病治疗效果较差。本研究观察了大剂量米托蒽醌和中剂量阿糖胞苷治疗30例难治性或复发的白血病的效果。米托蒽醌静脉注射总脐量为40mg/m2,阿糖胞苷剂量为每天花板-1.5g/m2,注射时间为3小时连续5天。26例病人获得完全缓解(缓解率为87%),1例(3.3%)部分缓解,治疗过程中无病例死亡。平均获得完全缓解所需的时间为30天左右。平均无病生存和存活时间分别为3.5和6个月。主要副作用为造血系统受抑。结果显示短程大剂量米托蒽醌联合阿糖胞苷治疗难治性或复发的白血病可获得较高的缓解率,值得推广应用。

  10. Late adverse effects of whole cranial irradiation in childhood hematological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Someya, Masanori; Nakata, Kensei; Nagakura, Hisayasu; Oouchi, Atsushi; Sakata, Kohichi; Hareyama, Masato [Sapporo Medical Coll. (Japan)

    2003-03-01

    The purpose of this study was to examine the late adverse effects of childhood hematological disorders treated with chemotherapy and radiotherapy including whole cranial irradiation at Sapporo Medical University Hospital. Twenty-eight patients were treated with chemotherapy and 18-24 Gy of prophylactic cranial irradiation (PCI) for acute lymphoblastic leukemia (ALL), and 14 patients were treated with 3-12.8 Gy of total body irradiation (TBI) and bone marrow transplantation (BMT) for ALL, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), malignant lymphoma, and aplastic anemia (AA). Age at diagnosis ranged from 2 to 15 years old, and 28 were males and 14 were females. All patients were disease-free more than 2 years after diagnosis. Of 42 patients, 4 patients had decreased height (less than -2 S.D.), 3 patients required hormone replacement therapy, 2 patients had mental retardation, 3 patients had leukoencephalopathy, and 1 patient had a second malignancy. Except for the cases of decreased height, 3 of 7 late adverse effects were occurred in patients who had relapse of disease, and the risk of the adverse effects seemed to be higher for those patients whose doses of PCI were 22 Gy or more, or who received an additional craniospinal irradiation due to relapse of disease, and 18 Gy of PCI did not increase the risk of adverse effects. (author)

  11. 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

  12. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients.

    Science.gov (United States)

    Sandahl, Julie Damgaard; Coenen, Eva A; Forestier, Erik; Harbott, Jochen; Johansson, Bertil; Kerndrup, Gitte; Adachi, Souichi; Auvrignon, Anne; Beverloo, H Berna; Cayuela, Jean-Michel; Chilton, Lucy; Fornerod, Maarten; de Haas, Valérie; Harrison, Christine J; Inaba, Hiroto; Kaspers, Gertjan J L; Liang, Der-Cherng; Locatelli, Franco; Masetti, Riccardo; Perot, Christine; Raimondi, Susana C; Reinhardt, Katarina; Tomizawa, Daisuke; von Neuhoff, Nils; Zecca, Marco; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M; Hasle, Henrik

    2014-05-01

    Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.

  13. Childhood Cancer: Leukemia (For Parents)

    Science.gov (United States)

    ... problems — such as Li-Fraumeni syndrome, Down syndrome , Klinefelter syndrome , neurofibromatosis , ataxia telangectasia, or Fanconi's anemia — have ... cancers. The doctor also will take a medical history by asking about symptoms, past health, the family's ...

  14. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  15. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    Energy Technology Data Exchange (ETDEWEB)

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2013-05-15

    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  17. 地西他滨联合CAG方案治疗复发难治性急性髓系白血病的护理分析%Nursing Analysis of Decitabine Combined With CAG Regimen in the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    刘迎庆

    2015-01-01

    Objective To investigate the effect of decitabine combined with CAG regimen in the treatment of relapsed and refractory acute myeloid leukemia and nursing effect. Methods Selected 15 cases of recurrence in our hospital of refractory acute myeloid leukemia patients who were treated with decitabine combined with CAG regimen,and gave symptomatic nursing,observed the nursing effect . Results After treatment,to complete remission in 9 patients,5 cases of patients with partial remission,1 cases were invalid. Conclusion Application of CAG combination solution treatment can achieve good treatment effect, at the same time, combined with effective, scientific, timely symptomatic nursing can effectively al eviate the adverse reaction, guide actively cooperate with treatment, help patients recover earlier.%目的:分析地西他滨联合CAG方案治疗复发难治性急性髓系白血病的护理效果。方法选取我院收治的15例复发难治性急性髓系白血病患者,均给予地西他滨联合CAG方案治疗,并给予对症护理,观察护理效果。结果在经过治疗后,完全缓解患者9例,部分缓解患者5例,无效患者1例。结论应用地西他滨联合CAG方案进行治疗可以取得良好的治疗效果,同时,结合有效、科学、及时的对症护理能够有效缓解的不良反应,引导患者积极配合治疗,帮助患者早日恢复健康。

  18. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

    Directory of Open Access Journals (Sweden)

    Bahareh Pezeshkian

    Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

  19. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    Science.gov (United States)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  20. Leukemia cutis

    Directory of Open Access Journals (Sweden)

    Varuna Mallya

    2015-01-01

    Full Text Available Patients with leukemia may show involvement of the skin. This skin involvement can be due to infiltration of skin by leukemic cells or it may be a part of nonspecific cutaneous manifestations. Leukemia cutis is the infiltration of neoplastic leucocytes or their precursors into the skin resulting in extensive clinical manifestations. Described mostly in acute myeloid leukemia and acute myelocytic monocytic leukemia, it is rare in chronic myeloid leukemia and is seen mostly during the blast crises. Its presence signals poor prognosis.

  1. Flow Cytometric DNA index, G-band Karyotyping, and Comparative Genomic Hybridization in Detection of High Hyperdiploidy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Nygaard, Ulrikka; Larsen, Jacob; Kristensen, Tim D;

    2006-01-01

    High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridiza...

  2. Bcl-2 family members in childhood acute lymphoblastic leukemia : relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome

    NARCIS (Netherlands)

    Salomons, GS; Smets, LA; Verwijs-Janssen, M; Hart, AAM; Haarman, EG; Kaspers, GJL; Van Wering, ER; Van Der Does-Van Den Berg, A; Kamps, WA

    1999-01-01

    We have found that, in addition to Bcl-2 and Bar, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-x(L), Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblastic leukemia (ALL). The patients were enrolled in the national study ALL-7 of

  3. Tratamento da recidiva da leucemia mielóide crônica após transplante de medula óssea alogênico utilizando mesilato de imatinibe: relato de três casos Treatment of chronic myelogenous leukemia relapse after allogeneic bone marrow transplantation with imatinib mesylate: report of three cases

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2006-06-01

    Full Text Available O mesilato de imatinibe (MI, inibidor seletivo da tirosinoquinase envolvido na patogênese da leucemia mielóide crônica (LMC, tem se constituído como terapia farmacológica de primeira linha para o tratamento desta doença. A infusão de linfócitos do doador (DLI tem sido considerada como tratamento padrão para recidiva da LMC após transplante de medula óssea (TMO alogênico, apesar de estar freqüentemente associado à ocorrência de doença do enxerto contra hospedeiro e mielossupressão. Por apresentar resultados satisfatórios e boa tolerabilidade no tratamento da LMC, os autores empregaram o mesilato de imatinib como terapêutica alternativa à DLI em pacientes que sofreram recidiva após o TMO. Obtiveram sucesso em dois casos, sendo que em um houve retorno comprovado do quimerismo do doador. No terceiro caso houve progressão da doença e o paciente foi encaminhado para segundo TMO. Desta forma, devido ao caráter recente do tema, este estudo descritivo sugere que esta opção terapêutica possa ser estudada como alternativa na recaída pós-TMO.Imatinib mesylate (MI, a selective tyrosine kinase inhibitor involved in the pathogenesis of chronic myelogenous leukemia (CML, has become the first-line treatment for this disease. Donor lymphocyte infusion (DLI has been considered as the standard treatment for relapse after allogeneic bone marrow transplantation (BMT, even though it is frequently associated with graft versus host disease and myelosuppression. Because of the satisfactory results and tolerance of the treatment of CML, the authors used MI as an alternative therapy for DLI in patients that relapsed after BMT. They obtained cytogenetic remission in two cases, with, in one case, proven conversion to the donor chimera. The third case evolved with progression of the disease and a second BMT was required. Since this is a new alternative, this descriptive study suggests it should be considered as an alternative therapy for relapse

  4. 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

  5. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

    Science.gov (United States)

    Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

    2009-10-01

    Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

  6. Cytarabine dose for acute myeloid leukemia

    NARCIS (Netherlands)

    B. Löwenberg (Bob); T. Pabst (Thomas); E. Vellenga (Edo); W. van Putten; H.C. Schouten (Harry); C. Graux (Carlos); A. Ferrant (Augustin); P. Sonneveld (Pieter); B.J. Biemond (Bart); A. Gratwohl (Alois); G.E. de Greef (Georgine); L.F. Verdonck (Leo); M.R. Schaafsma (Martijn); M. Gregor (Michael); M. Theobald; U. Schanz (Urs); J. Maertens (Johan); G.J. Ossenkoppele (Gert)

    2011-01-01

    textabstractBACKGROUND: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 m

  7. Cytarabine Dose for Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Lowenberg, Bob; Pabst, Thomas; Vellenga, Edo; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Biemond, Bart J.; Gratwohl, Alois; de Greef, Georgine E.; Verdonck, Leo F.; Schaafsma, Martijn R.; Gregor, Michael; Theobald, Matthias; Schanz, Urs; Maertens, Johan; Ossenkoppele, Gert J.

    2011-01-01

    BACKGROUND Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square

  8. An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

    Institute of Scientific and Technical Information of China (English)

    黄晓军; 郭乃榄; 任汉云; 张耀臣; 高志勇; 陆道培

    2003-01-01

    Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

  9. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Beverloo, H Berna; Kazemier, Karin M; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Pieters, Rob

    2005-12-01

    The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes. Normal bone marrow cells were more resistant to HDAC inhibitor FK228 induced cell killing than were cells from ALL patients with or without t(12;21). FK228 induced differentiation in ALL, irrespective of the presence of t(12;21).

  10. Papel da P190 BCR-ABL como parâmetro de recaída na leucemia mielóide crônica P190 BCR-ABL role in myeloid chronic leukemia relapse

    Directory of Open Access Journals (Sweden)

    Gabriela V. Andrade

    2008-08-01

    Full Text Available A leucemia mielóide crônica (LMC é uma desordem hematológica mieloproloferativa clonal causada por uma mutação em uma célula-tronco pluripotente, resultando na proliferação e acúmulo de células mielóides e seus progenitores. O cromossomo Philadelphia é o resultado de uma translocação recíproca de material genético entre os genes abl (Abelson murine leukemia no cromossomo 9, e o bcr (breakpoint cluster region no cromossomo 22, resultando na formação do gene quimérico BCR-ABL. Neste trabalho, 45 pacientes foram acompanhados de forma seqüencial, de acordo com as avaliações periódicas individuais, e 360 amostras foram selecionadas e analisadas pela técnica da reação em cadeia da polimerase (PCR através da técnica qualitativa para as isoformas características da P210BCR-ABL (b3a2 e b2a2 e P190BCR-ABL (e1a2. No nosso estudo no pré-TMO, observou-se uma prevalência das isoformas características da LMC (b3a2 e/ou b2a2, fato imprescindível para que o paciente fosse acompanhado dentro do protocolo da LMC. A isoforma e1a2, característica da LLA, foi detectada em 11 pacientes em conjunto com essas isoformas. A detecção do transcrito e1a2 foi avaliada quanto ao seu provável papel na LMC, e foi um dos parâmetros de avaliação deste estudo.Chronic myeloid leukemia (CML is a myeloproliferative clonal disorder caused by a mutation in a stem cell, resulting in the proliferation and accumulation of myeloid cells and their progenitors. The Philadelphia chromosome (Ph1 is a result of a mutual translocation of genetic material between the abl gene (Abelson murine leukemia in chromosome 9 and bcr gene (breakpoint cluster region in chromosome 22, resulting in the formation of the chimerical gene, BCR-ABL. In this work 45 patients were sequentially followed up in individual periodic evaluations, and 360 samples were selected and analyzed by PCR using the qualitative technique for isoforms characteristic of P210CR-ABL (b3a2 and b2a2

  11. 难治复发性急性髓系白血病患者缓解状态对异基因造血干细胞移植预后影响的分析%Impact of Disease Status on Outcomes of Allogeneic Hematopietic Stem Cell Transplantation in Patients with Refractory and Relapsed Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    周倩兰; 陈广华; 吴德沛; 唐晓文; 孙爱宁; 仇惠英; 金正明; 苗瞄; 付铮铮; 赵丙瑞; 施晓兰

    2012-01-01

    The study was aimed to evaluate the impact of disease status on the outcomes of allogeneic hematopietic stem cell transplantation (allo-HSCT) in patients with refractory and relapsed acute myeloid leukemia ( AML). 32 patients with refractory and relapsed AML received allo-HSCT after myeloablative conditioning regimen, including 17 patients in no-remission ( NR) and 15 patients in complete remission ( CR) at the time of transplant. Treatment related adverse events, relapse rate and leukemia free survival(LFS) were analyzed. The results showed that the parameters of sex, age, cytogenetic risk and transplant procedures were comparable between the two groups. 30 patients had successful engraftment, except one had graft failure and one died from severe veno-occlusive disease in the NR group. The incidences of aGVHD in NR group and CR group were 47. 1% (8 patients) and 33.5% (5 patients) respectively. Out of comparable patients, 5 from 9 patients in NR group developed with cGVHD, and 4 from 11 patients in CR group were subjected to cGVHD. There were no statistic difference in incidences of aGVHD and cGVHD between two group. Compa- red with CR group, NR group had a higher treatment-related mortality (29.4% vs 14.3% , P =0.392) and relapse rate (42.9% vs 26.7% p =0. 300), but there was no significant difference. With a median follow-up of 13 (1 - 124) months, 6 patients remained alive in both of the two groups ,and the 2 year LFS of them were parallel (35. 3% vs 40.0% , P =0.267). Among these 32 patients, overall survival (OS) was better in patients with age <35 years(P = 0.044) and with the appearance of cGVHD(P =0. 046). It is concluded that allo-HSCT is an effective salvage therapy for patients with refractory and relapsed AML, and the overall outcome seems unrelated to the disease status ( NR or CR) before transplantation. As such, for refractory and relapsed AML patients in non-remnission, performance of allo-HSCT to achieve long-term survival is feasible.%本研究

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

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

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

  13. Efficacy and safety analysis of the combination of cladribine, cytarabine, granulocyte colony-stimulating factor (CLAG) regime in patients with refractory or relapsed acute myeloid leukemia%CLAG方案治疗33例难治复发急性髓系白血病的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    段明辉; 张岩; 张梅; 韩潇; 张炎; 杨辰; 冯俊; 张路; 张薇

    2016-01-01

    Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia (AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three patients (16 males and 17 females) with refractory or relapsed AML were treated with one course of CLAG with a median age of 49 (14-68) years.According to FAB subtype,there were 22 patients with M2,and 11 with other types.According to NCCN criteria,there were 6,18 and 9 patients with favorable,intermediate and unfavorable risk respectively,including 5 with FLT3-ITD mutation.Of 16 refractory and 17 relapsed patients;the median previous chemotherapy courses were 2 (1-36).After one course of CLAG,78.8% (26/ 33) patients achieved hematological complete response (CR),with 93.8 %(15/16) in relapsed and 64.7 % (11/17) in refractory groups respectively.All five patients with FLT3-ITD mutation achieved CR.All patients had grade 4 neutropenia and thrombocytopenia and infection in different sites;three patients died early from infections.Five patients received allogeneic hematopoietic stem cell transplantation (alloHSCT).Ten patients relapsed and thirteen patients died after the median follow-up 142 (9-525) days.The median EFS and OS were 230 (9-525) and 419 (9-525) days respectively,which in CR group (n=26) were significantly longer than those in NR one (n=7) [447(165-525)d vs 52 (9-162)d,P< 0.001].Conclusions CLAG regimen was effective and well tolerable in patients with refractory or relapsed AML,with the CR rate in relapsed patients higher than in refractory counterparts.Control of infections was imperative for treatment.%目的 分析CLAG方案(克拉屈滨+阿糖胞苷+G-CSF)对难治复发急性髓系白血病(AML)的疗效及安全性.方法 回顾性分析2014年4月1日至2015年12月9日采用1

  14. Comparison of the overall treatment outcome of two protocols for childhood acute promyelocytic leukemia%两种方案治疗儿童急性早幼粒细胞白血病的总体预后对比分析

    Institute of Scientific and Technical Information of China (English)

    罗学群; 柯志勇; 黄礼彬; 官晓清; 张映川; 林苑; 张晓莉

    2010-01-01

    目的 对比先进国家的治疗方案和该院常规治疗方案对儿童急性早幼粒细胞白血病(APL)的疗效、预后及费用等,为改善中国APL患者的预后提供参考.方法 人组标准为15岁以下、FAB形态学符合APL和t(15;17)/PML-RARα阳性的患者.1999年11月至2004年9月共有16例符合入选条件,采用该院APL化疗方案治疗(包含诱导缓解后高强度的大剂量阿糖胞苷和米托蒽醌巩固治疗).2004年9月至2008年1月有14例入选,采用低强度的改良西班牙PETHEMA LPA99方案治疗.结果 用该院方案治疗的16例均纳入统计,3.5年无事件生存(EFS)率37.5%(s-x=0.121),放弃治疗6例(37.5%),死于诊断时颅内出血和治疗期间败血症各1例(6.3%),复发2例(12.5%).用改良PETHEMA方案治疗的14例患者3.5年EFS为79.6%(s-x=0.136),死于诊断时颅内出血1例(7.1%),复发1例(7.1%).两种方案对比,用改良PETHEMA方案治疗儿童APL在统计学上有较高的EFS(P=0.012),较低的败血症发生率(7.7%:77.8%,P=0.0015),较低的住院治疗费用(中位数3.52万元:15万元.P<0.0001)及随之较低的放弃治疗率.结论 用改良 PETHEMA 方案治疗儿童APL有较低的治疗并发症和较低的住院治疗费用,复发率无增加,减少了治疗相关毒性和治疗放弃率,使整体预后明显改善.%Objective For further improving the prognosis of childhood acute promyelocytic leukemia (APL) in China,the treatment efficacies, outcomes and costs of protocols for childhood APL between in developed countries and in our hospital were compared. Methods 30 cases aged <15 years were diagnosed according to the FAB classification and detection of PML-RARα rearrangement. From December 1999 to September 2004,sixteen eligible children were treated with an intensive in-house protocol including high-dose Ara-C and anthracycline for post remission treatment. From September 2004 to January 2008,14 cases enrolled were treated with a less intensive protocol modified from

  15. Aurora kinases as druggable targets in pediatric leukemia: heterogeneity in target modulation activities and cytotoxicity by diverse novel therapeutic agents.

    Directory of Open Access Journals (Sweden)

    Aarthi Jayanthan

    Full Text Available Leukemia is the most common pediatric malignancy, constituting more than 30% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and poor survival rates post relapse remain a challenge. Given this, more effective and innovative therapeutic strategies are needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for the regulation of several mitotic processes, have been identified as potential targets for cancer therapeutics. Elevated expression of Aurora kinases has been demonstrated in several malignancies and is associated with aberrant mitotic activity, aneuploidy and alterations in chromosomal structure and genome instability. Based on this rationale, a number of small molecule inhibitors have been formulated and advanced to human studies in the recent past. A comparative analysis of these agents in cytotoxicity and target modulation analyses against a panel of leukemia cells provides novel insights into the unique mechanisms and codependent activity pathways involved in targeting Aurora kinases, constituting a distinctive preclinical experimental framework to identify appropriate agents and combinations in future clinical studies.

  16. 地西他滨联合化疗治疗难治复发急性髓系白血病及骨髓增生异常综合征转化白血病的效果观察%Clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia and myelodysplastic syndrome transformed leukemia

    Institute of Scientific and Technical Information of China (English)

    韩波; 王朝晖; 邵纬; 王九河; 洪青; 范传波; 刘俊玲; 田猛; 王海霞

    2014-01-01

    目的 探讨地西他滨联合化疗治疗难治复发急性髓系白血病(AML)及骨髓增生异常综合征(MDS)转化AML的临床效果.方法 选取2013年2月至2014年3月住院治疗的难治复发AML患者19例及MDS转化AML患者4例,所有患者给予地西他滨联合CAG方案进行治疗,评估患者治疗效果及不良反应.结果 经过1个疗程治疗后,14例(60.9%)完全缓解,2例(8.7%)部分缓解,7例(30.4%)无效,总有效率69.6%,不同染色体核型患者临床治疗效果差异具有统计学意义(P<0.05).23例患者出现不同程度的骨髓抑制,其中Ⅰ~Ⅱ级中性粒细胞减少2例,Ⅲ~Ⅳ级21例,中性粒细胞减少中位时间13 d;Ⅲ~Ⅳ级贫血23例;Ⅲ~Ⅳ级血小板减少23例,血小板减少中位时间16d.Ⅰ~Ⅱ级出血20例,Ⅲ~Ⅳ级3例.Ⅰ~Ⅱ级胃肠道反应1例.Ⅰ~Ⅱ级肝功能异常1例.所有患者随访至2014年3月31日,生存20例,死亡3例,中位总生存期3.1个月,1年累积生存率86%.结论 地西他滨联合化疗治疗难治复发AML及MDS转化白血病的临床缓解率高,不良反应少;染色体核型可能是影响治疗效果的重要因素.%Objective To investigate the clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed leukemia.Methods 19 patients with refractory and relapsed AML and 4 cases of patients with MDS transformed AML were enrolled from February 2013 to March 2014.All cases were treated with decitabine combined with CAG regimen.The clinical effects and adverse reactions were evaluated.Results After a course of treatment,14 cases (60.9 %) were complete remission,2 cases (8.7 %) were parrtial remission,7 cases (30.4 %) were non-remission,and the total efficiency rate was 69.6 %.The differences of clinical outcomes among different karyotypes were statistically significant (P < 0.05).There were

  17. Metodologia diagnóstica e tratamento da recaída após transplante de medula óssea em paciente com leucemia promielocítica aguda Diagnostic methodology and treatment of relapse after bone marrow transplantation in a patient with acute promyelocitic leukemia

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2000-12-01

    fundamental manner. The early diagnosis of relapse is sustented by the ability to detect the minimal residual disease. The methodology using flowcitometry, conventional cytogenetic, fluorescence in situ hybridization (FISH and polymerase chain reaction (PCR allow the diagnosis of these residual clone that are responsible for relapse. L.M.S.O., 54 year old lady, was diagnosed with promyelocitic leukemia (AML M3 in 1997. She was submitted to an autologous bone marrow transplantation in 09/01/98 as consolidation therapy. Two years after the transplant she was diagnosed with a molecular relapse by RT-PCR sequentially performed. The use of all-trans-retinoic acid (ATRA was able to induce a new molecular remission. The mechanism of action of ATRA to induce remission in AML M3 is not well established. This drug can be use in relapse. In the case that was presented, the early diagnosis that leaded to this good result happened because of a well planned post transplant evaluation. These variables of selection, conditioning and follow up should be well studied to plan an adequate and prolonged post transplant follow up, allowing better results with the procedure.

  18. Relapsing pityriasis rosea.

    Science.gov (United States)

    Drago, Francesco; Ciccarese, Giulia; Rebora, Alfredo; Parodi, Aurora

    2014-01-01

    To assess the prevalence of relapses of pityriasis rosea (PR), a retrospective cohort study investigated all PR cases diagnosed in Genoa between 2000 and 2013 and followed them up to today. Of 570 cases, 21 (3.7%) relapsed. Most of them had a single episode, but 4 had two episodes and 2 had three episodes. The herald patch was always absent, size and number of the lesions were reduced, and duration was shorter than that of the primary episodes. Constitutional symptoms were present, though less severe than in the primary eruption. Most recurrences occurred within 1 year (16/21, 76.2%). Men outnumbered women and the mean age of the relapsing patients (20.3 years) was higher than that for the primary episode. A pathogenetic hypothesis is provided: since PR is associated with reactivation of human herpesvirus 6/7, a parallelism with other typical reactivating human herpesviruses (varicella zoster virus and Epstein-Barr virus) has been established.

  19. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...

  20. 急性白血病并肺部真菌感染57例早期诊断与防治策略%Early Diagnosis,Treatment and Prevention of Childhood Acute Leukemia Complicated with Pulmonary Fungal Infection

    Institute of Scientific and Technical Information of China (English)

    邵静波; 蒋慧; 李红; 陆正华; 杨静薇; 杨为群

    2011-01-01

    Objective To analyze the clinical features and investigate the early diagnosis and treatment of childhood acute leukemia complicated with pulmonary fungal infection (PFI). Methods The clinical data of 132 cases of childhood acute leukemia were retrospectively analyzed. Fifty -seven patients, who had the PFI,including 5 times with confirmed diagnosis,30 times with clinical diagnosis,and 25 times with recommended diagnosis were diagnosed according to European Organization for Research and Treatment of Cancer. Results 1. The incidence rate of PFI in the childhood acute leukemia was 43.18% (57/132 cases). The median time from occurring PFI to confirmed leukemia was 7.2 months,among which 70% (42/60 cases) were within 12 months while 30% ( 18/60 cases) more than 12 months. 2. The representation of chest CT was multiform,mainly for inflammatory exudate,interstitial changes,and cloud flocculeut nodules. The severe patients were accompanied by pleural effusion or acute respiratory distress syndrome(ARDS). 3. Seventy -one point seven percent(43/60 cases)of PFI were neutropenia ( < 1.5 × 109 L-1 ) ,in which 40.0% were ngranulocytosis ( < 0. 5 × 109L-1 ). 4. The positive rate of fungal G test was 70.5% ( 31/44 cases) wille negative was 29.5% ( 13/44 cases). Totally 7 candida strains and 2 mierozyme strains were obtained from 57 cases of PFI. 5. The total cure rate was 95.0%. Cure rates of single drug and combined anti fungal were 53.3% and 41.7%. Conclusions 1. Fungal infection is one of the main pathogens in childhood acute leukemia complicated by severe infection. 2. Chest CT shows important value in the diagnosis of PFI. The positive rate of microorganism culture is low in children. 3. Early diagnosis and treatment are the key to improve curative effect. Better prognosis can be gained if those patients with early respiratory failure or ARDS get oxygen or mechanical ventilation in time.%目的 分析急性白血病并肺部真菌感染(PFI)患儿的

  1. 农药暴露与儿童急性白血病关系的病例-对照研究%A case-control study on correlation of pesticide exposure with childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    张妍; 金萍; 田英; 朱莎; 高宇; 王筱金; 陈涛; 杨友; 汪国权; 胡国华; 施蓉

    2011-01-01

    Objective To evaluate the correlation of pesticide exposure with childhood acute leukemia. Methods An exploratory case-control study was conducted among childhood acute leukemia patients under 15 years old in Shanghai, China. From January 1st,2006 to December 31st,2008, a total of 80 newly diagnosed acute leukemia patients were recruited from Shanghai Children's Medical Center for the case group. Another 96 age-matched patients who visited the hospital for health examination, pediatric treatment or osteological therapy excluding hematological system diseases and neoplastic disease, were recruited for the control group. A questionnaire survey was conducted in both groups; and a 30-40 ml random urine sample was collected from each participant. Five types of organophosphorus pesticide metabolites was then detected among the samples, using Gas Chromatography with Flame Spectrophotometry. Results According to result of the questionnaire survey, more participants (55.0% (44/80)) in case group than in the control group (33.3% (32/96)) reported using mosquitocide, which might increase the risk of childhood acute leukemia (OR = 2.444;95% CI:1. 326-4. 506). At the same time, the detection showed that the concentration (median) of organophosphate metabolites diethyl phosphrate,dimethyl phophrate,dimethyl thiophosphrate,diethyl thiophosphrate and diethyl dithiophosphrate in case group were 0. 0682,0. 0082,0. 0183,0. 0233,0. 4259 μg/g Cr, which were all significantly higher than in control group (0. 0865,0. 0025,0. 0112,0. 0123,0. 1207 μg/g Cr) except the concentration of diethyl phosphrate (Z =-1.081, P = 0. 279). The difference showed statistical significance (Z =-5. 752,-2. 800,-3.316,-8. 120, P < 0. 05). Conclusion Pesticide exposure may be one of the risk factors for childhood acute leukemia.%目的 探讨农药暴露与儿童急性白血病发病之间的关系.方法 选取2006年1月1日至2008年12月31日就诊于上海儿童医学中心,年龄小于15周岁的80

  2. Relapsing polychondritis: commentary

    Directory of Open Access Journals (Sweden)

    R.D. Altman

    2011-09-01

    Full Text Available Relapsing Polychondritis (RP is a multisystem disease of unknown etiology characterized by episodic inflammation of cartilage and potentially progressive degeneration of cartilaginous tissue, such as auricular, nasal and laryngotracheobronchial cartilage. However, many other proteoglycan- rich structures may be involved, such as inner ear, eyes, blood vessels, heart and kidneys (1- 4. RP was first described by Jacksh-Wartenhorst in 1923, who named it “polychondropathia” (5. Pearson et al. (6 introduced the term “relapsing polychondritis” in 1960...

  3. Treatment of Children with APL (Acute Promyelocytic Leukemia)

    Science.gov (United States)

    ... it can be put into a second remission. Arsenic trioxide is a drug that is very effective ... Childhood Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To ...

  4. Analyses of karyotypic characteristics and prognosis in pediatric acute myeloblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    阮敏

    2012-01-01

    Objective Acute myeloblastic leukemia(AML) accounts for 15 to 25 percent of childhood acute leukemias. Cytogenetic information is important for diagnosis,classification and prognosis of AML. Our aim was to analyze the relationship between karyotypic characteristics and prognosis of childhood

  5. Prophylactic G-CSF mobilized donor lymphocytes infusion after non-myeloablative stem cell transplantation prevents relapse in patients with high-risk leukemia%预防性G-CSF动员后供者淋巴细胞输注对高危白血病患者非清髓造血干细胞移植术后复发及移植物抗宿主病的影响

    Institute of Scientific and Technical Information of China (English)

    赵红霞; 孙万军; 李洁; 乔均晓; 黄雅静; 胡海兰; 艾辉胜

    2013-01-01

    Objective To evaluate the anti-leukemia effects of prophylactic G-CSF mobilized donor lymphocytes infusion (pG-DLI) and its relationship with the incidence of graft-versus-host disease (GVHD) in high-risk leukemia patients with non-myeloblative stem cell transplantation (NST).Methods 12 patients with high-risk leukemia were analyzed,including Ph+ acute lymphocytic leukemia (n=1),acute leukemia (AL) with persistent non-complete remission (n=2),acute myeloid leukemia (AML) with central nervous system (CNS) relapse (n=3),hybrid AL (n=1),secondary AML evolving from myelodysplastic syndrome (MDS/AML) (n=2),chronic myeloid leukemia in accelerated phase (CML-AP) (n=1),CML in blastic phase (CML-BP) (n=2).All patients received non-myeloablative conditioning and pG-DLIs were administered 30-40 days post transplantation if no signs of GVHD were present.The percentage of donor cell chimera was analyzed by short tandem repeat-polymerase chain reaction (STR-PCR) just before and after pG-DLI.The incidence of leukemia relapse and GVHD were observed.Results 12 high-risk leukemia patients with a median age of 38 (range:29-52) years received pG-DLI at a median interval of 35 (32-40) days.The median numbers of infused mononuclear cells (MNCs),CD34+,and CD3+ cells/kg recipient body weight was 2.3× 108/kg,1.7× 106/kg,and 0.6× 108/kg,respectively.10 of 12 patients had full donor chimera before pG-DLIs and conversion from mixed to full donor chimera occurred in the other 2 patients shortly after pG-DLI.Grade Ⅱ acute GVHD (aGVHD) was observed in only 2 patients and chronic GVHD (cGVHD) developed in 6 patients,including involvement of skin (n=3),skin and intestine (n=2),liver (n=1).1 patient died of cGVHD.With a median follow-up of 40 (24-64) months,7 patients are alive in remission,with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of the same 58.3%.Conclusion Our findings indicate that pG-DLI after NST does not increase the risk of aGVHD,but could

  6. 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.

  7. Characterization of leukemia-associated minor histocompatibility antigens as targets in anti-leukemic immunotherapy

    NARCIS (Netherlands)

    Rijke, Björn de

    2007-01-01

    This thesis describes the characterization and identification of CTL-defined leukemia-associated minor histocompatibility antigens (mHAg) for the development of novel cellular immunotherapeutic approaches to successfully treat patients with relapsed hematopoietic malignancies after allogeneic stem c

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

    Science.gov (United States)

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

  9. Pregnancy, Maternal Tobacco Smoking, and Early Age Leukemia in Brazil

    OpenAIRE

    2012-01-01

    Background: Cigarette smoking has been associated with acute myeloid leukemia but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia is unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (< 2 yr.) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999-2007. Data were collected by ...

  10. Progressive-Relapsing MS (PRMS)

    Science.gov (United States)

    ... a Local Support Group Ask an MS Navigator Edward M. Dowd Personal Advocate Program Connect with Peers ... relapsing MS (PRMS) Types of MS Clinically Isolated Syndrome (CIS) Relapsing-remitting MS (RRMS) Primary progressive MS ( ...

  11. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Because the location of the damage is so variable, no two people have exactly the same symptoms. ... relapsing-remitting MS (RRMS) Learn More Learn More Research in relapsing-remitting MS (RRMS) Learn More Learn ...

  12. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined by inflammatory ... remitting MS (RRMS) Learn More Learn More Research in relapsing-remitting MS (RRMS) Learn More Learn More ...

  13. 地西他滨联合CAG方案治疗复发难治性急性髓系白血病的临床分析%Clinical Analysis of Decitabine and CAG Scheme in Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    白晶; 王晓华

    2016-01-01

    Objective To study the effect of decitabine and CAG combination regimen for relapsed and refractory acute myeloid leukemia(AML). Methods 45 patients with refractory AML recurrence were divided into two groups,control group,the implementation of the CAG regimen for observation group added to west treatment,combination analysis of two groups of therapeutic effect. Results The observation group treatment remission rate 81.8%higher than that of control group 81.8%,significant difference(P 0.05). Conclusion Decitabine and CAG scheme for patients with refractory AML combination effect is good,worthy of clinical promotion.%目的:探讨地西他滨联合CAG方案治疗复发难治性急性髓系白血病(AML)的效果。方法将复发难治性AML患者45例分为两组,对照组实施CAG方案治疗,观察组添加地西他滨联合治疗,分析两组治疗效果。结果观察组治疗缓解率81.8%高于对照组的60.9%,差异具有统计学意义(P<0.05)。观察组不良反应发生率50.0%;对照组不良反应发生率52.2%,差异无统计学意义(P>0.05)。结论地西他滨联合CAG方案治疗复发难治性AML患者效果良好。

  14. 父母亲化学物质暴露与儿童急性白血病发病关系的探讨%Relationship between parental exposure to chemicals and risk of childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    施蓉; 高宇; 张妍; 高怡瑾; 朱莎; 王筱金; 金萍; 田英

    2013-01-01

    目的 探讨父母亲化学物质暴露与儿童急性白血病发病的关系.方法 选取2009年1月1日至2010年12月31日所有就诊于上海地区3家儿童医院年龄小于15周岁的201例新发急性白血病的儿童,在病例所在医院的儿童保健门诊或骨科选取同性别同年龄的对照儿童201例,对其母亲进行面对面的访谈式调查.结果 母亲孕前3个月至孕期总化学物质(柴油、汽油、油漆、杀虫剂、农药、除草剂、化肥)接触史(OR=2.9,95%CI=1.1~7.8)及父亲在母亲孕前3个月接触杀虫剂(OR=10.1,95%CI=1.2~82.9)、化肥(OR=9.5,95%CI=1.1~79.6);母亲孕前从事农业、林业工作(OR=8.4,95%CI=1.4~50.2);孕前及孕期从事纺织、皮革、装潢、汽修(孕前:OR =3.0,95%CI=1.2~7.9;孕期:OR=3.2,95%CI=1.1~9.6);父亲从事农业、林业(OR =9.6,95%CI=2.1~44.8)及纺织、皮革、装潢、汽修工作(OR=2.3,95%CI=1.1~5.0)等因素可能是儿童急性白血病发病的危险因素.结论 父母亲化学物质暴露可能会增加后代患急性白血病的风险.%Objective To investigate the relationship between parental exposure to chemicals and the risk of childhood acute leukemia.Methods An exploratory case-control study was conducted among 201 new cases of childhood acute leukemia under 15 years old who went to 3 children's hospitals in Shanghai,China from January 1,2009 to December 31,2010,as well as 201 sex-and age-matched children (as controls) who went to the child health care clinic or department of orthopedics in the above hospitals.A survey was performed by face-to-face interviews with children's mothers.Results The risk factors for childhood acute leukemia might include maternal exposure to total chemicals (diesel oil,gasoline,paints,insecticides,pesticides,herbicides,and chemical fertilizers) from 3 months before pregnancy to the end of pregnancy (OR=2.9,95%CI=1.1~7.8),paternal exposure to insecticides (OR=10.1,95%CI=1.2~82

  15. 地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病临床观察%Clinical observation of decitabine combined with low-dose MA/DA regimen in the treatment of patients with refractory or relapsed acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    梁艳; 唐元艳; 熊涛; 邓鸣凤; 张利铭; 黄知平

    2016-01-01

    目的:观察地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病患者的疗效及安全性。方法选取2012年8月至2015年6月本院收治的18例复发难治性急性髓系白血病患者,予以地西他滨联合减量MA [地西他滨20 mg/(m2· d),d1~5;米托蒽醌8~12 mg/m2,d6~8;阿糖胞苷100 mg/m2,d6~8]/DA方案[地西他滨20 mg/(m2· d),d1~5;柔红霉素40~45 mg/m2,d6~8;阿糖胞苷100 mg/m2,d6~8],观察患者临床疗效及不良反应。结果18例患者中完全缓解(CR)6例(33.3%),部分缓解(PR)5例(27.8%),总有效率(ORR)为61.1%;8例染色体异常患者治疗后1例获完全细胞遗传学缓解,3例部分细胞遗传学缓解,总有效率为50.0%。不良反应主要为骨髓抑制及继发感染,经过输血和抗感染等支持治疗均可以耐受。随访至2015年6月,患者中位生存为8个月。结论地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病在血液学及细胞遗传学上可以获得较好疗效,且毒副作用较轻,耐受性良好。%Objective To investigate the clinical efficacy and safety of decitabine combined with the reduced quantity of cytarabine (Ara-C) and mitoxantrone (MIT) regimen in the treatment of patients with refractory or re-lapsed acute myeloid leukemia. Methods Eighteen cases with refractory or relapsed acute myeloid leukemia in our hospital from August 2012 to June 2015 were treated with decitabine combined with reduced quantity of MA regimen (decitabine 20 mg/(m2· d), d1~5; MIT 8~12 mg/m2, d6~8;Ara-c100 mg/m2, d6~8)/DA regimen (decitabine 20 mg/(m2· d), d1~5; DNR 40~45 mg/m2, d6~8;Ara-c100 mg/m2, d6~8), and the clinical outcome and adverse events were recorded. Results Among 18 patients, 6 (33.3%) patients achieved complete remission (CR), and 5 (27.8%) were partial remission (PR), with overall remission rate (ORR) of 61.1%;After treatment, of 8 patients with chromosomal ab-normalities, 1 patient

  16. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

  17. Combination therapy of imatinib and donor lymphocyte infusion for chronic myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation%伊马替尼联合供者淋巴细胞输注治疗造血干细胞移植后慢性粒细胞白血病复发

    Institute of Scientific and Technical Information of China (English)

    钱思轩; 李建勇; 吴汉新; 张晓艳; 张苏江; 洪鸣; 张闰; 孙雪梅

    2008-01-01

    Objective To evaluate the efficiency of combination therapy of imatinib and donor lymphocyte infusion (DLI) for chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Patient 1 received peripheral blood stem cell transplantation from her HLA-identical sister, patient 2 received bone marrow transplantation from her HLA-identical brother and patient 3 received the transplantation of bone marrow in combined with peripheral blood stem cells following a conditioning regimen. For the prophylaxis of graft-versus-host disease (GVHD), patient 1 was treated with cyclosporine A (CsA) and mycophenolate mofetil (MMF), patient 2 with CsA, short course methotrexate (MTX), anti-thymocyte globulin and anti-CD25 monoclonal antibody,and patient 3 with CsA, MTX and MMF. They were treated with imatinib and DLI in hematologic relapse after HSCT. Results Patient 1 was treated with DLI on day + 30,+ 50 and + 70 after allo-HSCT,with CD3+ T lymphocyte cells of 0. 5 × 107 /kg,1.0×107 /kg and 2. 0 × 107 /kg respectively. She obtained a full donor ehimerism on short tandem repeats polymerase chain reaction (STR-PCR). She was treated with imatinib 400 nag daily and DLI with CD3+ T lymphocyte cells of 2. 5×107 /kg on day + 120 days for progression of disease. The bone marrow on day + 180 showed a full donor chimerism on STR-PCR. She died of extramedullary relapse 17 months after alloHSCT. For patient 2,cytogenetic analysis of bone marrow showed a male karyotype of 46,XY without any cytogenetic abnormalities, 100% cells on interphase nuclei revealed the XY genotype in the sex chromosome fluorescence in site hybridization(FISH) analysis and BCR-ABL fusion gene was negative on day + 35 after alIo-HSCT. Patient 2 relapsed on day + 100 after allo-HSCT,CsA was withdrawn and DLI with CD3+ T lymphocyte cells of 3. 9 × 107 /kg in combination with imatinib 500 mg was given daily. After treatment with DLI and imatinib for 30 days

  18. Plasma cell leukemia

    DEFF Research Database (Denmark)

    Fernández de Larrea, C; Kyle, R A; Durie, B G M

    2013-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic......-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds...... regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding...

  19. 地西他滨联合半量CAG治疗复发难治性急性髓细胞白血病的疗效分析%Analysis of the Efficacy of Decitabine Combined with Half Quantity of CAG Regiment for the Treatment of Refractory or Relapsed Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    高然; 于锦香; 高峰; 蔡大利; 王柏勋; 潘登; 张蕊; 颜晓菁; 李艳

    2013-01-01

    [目的]探讨地西他滨联合半量阿克拉霉素+阿糖胞苷+粒系集落刺激因子(CAG)方案治疗复发难治性急性髓细胞白血病(AML)的疗效.[方法]回顾性分析2012年2~10月在本院血液科接受地西他滨治疗的7例复发难治AML患者的临床资料,评价其疗效和不良反应.[结果]完全缓解患者3例,部分缓解患者2例,无效患者2例,总有效率为71.4%(5/7);血液学不良反应发生率为100%,感染发生率为71.4%(5/7),轻度肝功能损伤率42.9%(3/7),无严重出血、恶心呕吐不良反应.[结论]地西他滨联合半量CAG可有效治疗复发难治性急性髓细胞白血病,虽然血液学不良反应较重,感染的发生率较高,但患者基本上可耐受,给予相应抗炎及支持治疗可得到有效控制.%[Objective]To explore clinical efficacy of decitabine combined with half quantity of aclacinomycin+cytarabine+granulocyte-colony stimulating factor(CAG) regiment for the treatment of refractory or relapsed acute myeloid leukemia(AML).[Methods]Clinical data of 7 patients with refractory or relapsed AML treated with decitabine in hematology department of our hospital from Feb.2012 to Oct.2012 were analyzed retrospectively.The efficacy and adverse reaction were evaluated.[Results] Of all patients,3 patients achieved complete remission,and 2 patients achieved partial remission.The overall response rate was 71.4%(5/7).The incidence of hematologic toxicity was 100%,and the infection rate was 71.4% (5/7),and the incidence of mild liver injury was 42.9% (3/7).No severe bleeding,nausea and vomiting were observed.[Conclusion] Decitabine combined with half quantity of CAG regiment can effectively treat refractory or relapsed AML.Although the hematologic toxicity is more serious and the infection rate is higher,patients can tolerate them.Anti-inflammatory and supportive treatment should be given to control them.

  20. Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine

    2012-01-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during.......06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX2–7 patients (P = 0.40) but did for TMP/SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP/SMX2–7 and TMP/SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP/SMX2–7 and TMP....../SMXnever patients (0.83 vs. 0.83; P = 0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy...

  1. Leukemia cutis

    Directory of Open Access Journals (Sweden)

    Angoori G Rao

    2012-01-01

    Full Text Available Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions. Leukemia cutis may follow, precede or occur concomitantly with the diagnosis of systemic leukemia. A 50-year-old woman presented with asymptomatic multiple cutaneous nodules all over the body of 4 months duration. Cutaneous examination showed multiple hyperpigmented nodules and plaques involving face, trunk, and extremities. Peripheral smear showed abnormally elevated leucocyte count (TLC-70,000 with abnormal cells: myeloblasts 40%, promyelocytes 8% and myelocytes 39%. Auer rods were present in few myeloblasts. Bone marrow aspiration showed increased cellularity, erythroid hyperplasia with megaloblastic change, increased myeloblasts with maturation arrest. Immunohistochemistry showed strongly positive myeloperoxidase infiltrating cells and negative for CD20 and CD3 consistent with the diagnosis of AML-M 2 with leukemia cutis. This case is reported for its rarity.

  2. Understanding Leukemia

    Science.gov (United States)

    ... material presented in this publication Jane Liesveld, MD Professor, Department of Medicine, Hematology/Oncology Clinical Director, Blood ... of leukemia cell. The marrow has two main jobs. The first job is to form myeloid cells. ...

  3. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

  4. 成人急性淋巴细胞白血病复发因素分析及风险度评价%Analysis of relapse factors and risk assessment of adult acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    陈培翠; 王婷玉; 邹德慧; 邱录贵; 张翠仙; 张耀; 刘桂芬; 罗天娥

    2013-01-01

    目的 探讨影响成人急性淋巴细胞白血病(ALL)患者复发的因素,建立预后指数(PI)的计算模型,为改进成人ALL防治策略提供依据.方法 收集2008年8月至2011年11月中国医学科学院血液病医院收治的104例成人ALL患者资料,采用哑变量分层COX回归构建预测模型,生存率的估计采用分层Kaplan-Meier法;生存率的比较采用Log-rank检验.并计算个体PI值,然后按其分组来估计患者期望生存率.结果 成人ALL患者中位生存时间为22.00个月(95% CI 17.00~27.00个月);COX回归分析表明:设治疗方式为哑变量,分层结果显示化疗组成人B-ALL患者复发风险比自体移植组高(RR值为2.052,95%CI 0.877~4.799,P=0.007);初诊血红蛋白含量小于100 g/L(RR值为0.186,95% CI 0.068~0.512,P=0.001)、合并中枢神经系统白血病(CNSL)(RR值为7.767,95% CI 2.951~20.433,P=0.001)、巩固化疗疗程数在3个以下(RR值为0.445,95%CI0.211~0.940,P=0.034)和Ph染色体阳性(RR值为2.771,95%CI1.353~5.674,P=0.005)是影响成人B-ALL患者复发的危险因素.根据PI值分组,以PI=0.58为基准,可预测患者生存概率.结论 初诊血红蛋白含量小于100g/L、合并CNSL、巩固化疗疗程数在3个以下及Ph染色体阳性是影响成人B-ALL患者复发的因素;利用PI值分组预测患者生存概率可为成人ALL患者的临床个体化治疗及预后评价提供参考.%Objective To explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults.Methods 104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled.COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model;Kaplan-Meier method and Log-rank test were used to estimate and compare the survival

  5. Dietary resveratrol does not delay engraftment, sensitize to vincristine, or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

    Science.gov (United States)

    Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Although resveratrol is able to kill high-risk leukemia in vitro, this agent has not been evaluated agai...

  6. Efficacy of Auto-DC-CIK Adoptive Immunotherapy in Childhood Acute Leukemia%自体DC-CIK过继免疫治疗儿童急性白血病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周东风; 蔡和花; 潘峰; 白燕; 翟丽娜; 吴耀辉; 金润铭; 孟浦

    2011-01-01

    Objective To evaluate the clinical efficacy and safety of co-cultured dendritic cells with cytokine-induced-killer cells(DC-CIK)adaptive immunotherapy in treating childhood acute leukemia who have attained cellular complete remission after chemotherapy. Methods Forty-seven children with acute leukemia who have attained complete remission after chemotherapy were enrolled in this retrospective analysis. Minimal residual disease(MRD)was positive in 9 out of the 47 cases. DC-CIK were transfused to the children twice after cultivation,amplification and quality test in vilro. The hematological and genetic changes, MRD and cellular immune function were monitored regularly after the treatment. Results Forty-seven patients had successfully received a total of 61 courses of DC-CIK transfusion. The median time of follow-up was 41 months(range from 5 to 72 months). Thirty-six out of the 38 MRD-negative cases stayed continuous complete remission(CCR) including a acute lymphoblastic leu-kemia( ALL) child who had hepatitis B with HbsAg+/eAg+/cAb+. The very child was intolerant to chemotherapy because of liver dysfunction,and then received DC-CIK therapy after 5 courses of chemotherapy. During 60 months of follow-up period,he has always stayed CCR. His liver function recovered while the hepatitis B with HbsAg+/eAg+/cAb+ turned to be HbsAg+/ eAb+/cAb+. The MRD was monitored by flow cytometry or real-time quantitative polymerase chain reaction(RQ-PCR). Of the 9 cases positive for MRD,8 cases turned to be negative after DC-CIK therapy. The peripheral T-lymphocyte subsets showed that the proportion of CD3+ CD8+ cells was increased distinctly. Conclusion DC-CIK therapy in combination with or followed by chemotherapy does great well in MRD clearance for childhood acute leukemia. It is a novel hopeful therapy contributing to the improved clinical management of children with acute leukemia that requires more basic and clinical research.%目的 回顾性评估化疗联合自体共培养

  7. Identifying therapeutic targets by elucidating signaling pathways in pediatric lymphoid leukemias

    NARCIS (Netherlands)

    van der Sligte, Naomi Eline

    2015-01-01

    Despite intensive chemotherapy, acute lymphoblastic leukemia (ALL) relapse is still a major cause of cancer-related death in children and the survival of children with lymphoid blast crisis chronic myeloid leukemia (CML-LyBC) is even worse. Further improvements in outcome, achieved by dose optimizat

  8. Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

    Directory of Open Access Journals (Sweden)

    Juliane Morando

    2012-01-01

    Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

  9. Infections During Induction Therapy of Protocol CCLG-2008 in Childhood Acute Lymphoblastic Leukemia: A Single-center Experience with 256 Cases in China

    Institute of Scientific and Technical Information of China (English)

    Si-Dan Li; Yong-Bing Chen; Zhi-Gang Li; Run-Hui Wu; Mao-Quan Qin; Xuan Zhou; Jin Jiang

    2015-01-01

    Background:Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL).Methods:We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital.Results:There were 65 infectious complications in 50 patients during vincristine,daunorubicin,L-asparaginase and dexamethasone induction therapy,including microbiologically documented infections (n =12; 18.5%),clinically documented infections (n =23; 35.3%) and fever of unknown origin (n =30; 46.2%).Neutropenia was present in 83.1% of the infectious episodes.In all,most infections occurred around the 15t1h day of induction treatment (n =28),and no patients died of infection-associated complications.Conclusions:The infections in this study was independent of treatment response,minimal residual diseases at the end of induction therapy,gender,immunophenotype,infection at first visit,risk stratification at diagnosis,unfavorable karyotypes at diagnosis and morphologic type.The infection rate of CCLG-2008 induction therapy is low,and the outcome of patients is favorable.

  10. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A.

    Science.gov (United States)

    Liang, Der-Cherng; Liu, Hsi-Che; Yang, Chao-Ping; Jaing, Tang-Her; Hung, Iou-Jih; Yeh, Ting-Chi; Chen, Shih-Hsiang; Hou, Jen-Yin; Huang, Ying-Jung; Shih, Yu-Shu; Huang, Yu-Hui; Lin, Tung-Huei; Shih, Lee-Yung

    2013-04-11

    Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with polymerase chain reaction-based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III, and 5.6% class IV. FLT3-internal tandem duplication was most frequent, and 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-partial tandem duplication. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2, and IDH1 mutations were associated with specific genetic subtypes.

  11. Estratégias de tratamento da leucemia linfóide crônica recidivada ou resistente incluindo o transplante de célula progenitora hematopoiética Strategies of treatment for relapsed or resistant chronic lymphocytic leukemia including to hematopoietic progenitor cell transplantation

    Directory of Open Access Journals (Sweden)

    Cármino A. Souza

    2005-12-01

    pacientes com doador HLA idêntico, preferentemente mais jovens (Despite much progress in therapy, chronic lymphocytic leukemia, the most common leukemia in the Western world, remains incurable. The use of fludarabine alone or associated to cyclophosphamide and/or mitoxantrone or doxorubicin improved the objective response, including complete response (also molecular and the progression- and relapse-free-survival. Several authors have suggested the introduction of monoclonal antibodies in order to improve the results. Despite that, all treated patients will further relapse or progress and salvage treatment should be used. In the present state-of-the art, salvage treatment is similar to those used as front line therapy. Indeed the criteria to start treatment are the same as defined by NCI for the front line therapy. Fludarabine alone or associated should be the therapy of choice for relapsed patients also for those previously treated with fludarabine. The use of monoclonal antibodies particularly rituximab is a good option although this procedure has not been considered as the standard therapy until now. Alemtuzumab is a very efficient monoclonal antibody and promotes significant benefits in clinical and hematological responses also in heavily treated or fludarabine refractory patients. The HPCT has limited indication due to the risks of high dose therapy in elderly patients. Autologous HPCT may be used specifically in young patients, if possible in complete remission, in order to improve the progression- or disease-free-survival. Conventional or with reduced intensity allogeneic HPCT may be used in patients presenting with a sibling donor particularly those under 60 years old, in fludarabine refractory patients or in patients presenting with unfavorable cytogenetics (17p-, with a curative objective.

  12. Correlation between Different miRNA Profiles and Childhood Acute Lymphoblastic Leukemia Relapse%miRNA表达谱改变与儿童急性淋巴细胞白血病复发的相关性

    Institute of Scientific and Technical Information of China (English)

    程玉才; 黄礼彬; 王丽娜; 梁燕妮; 罗学群

    2014-01-01

    [目的]筛选与儿童急性淋巴细胞白血病(ALL)预后相关的microRNA (miRNA),旨在寻找与ALL预后相关的分子标记物,为临床ALL患儿分层治疗提供实验室依据.[方法]采用基因芯片技术检测10例初发-缓解配对的ALL患儿骨髓细胞的miRNA表达谱(基因芯片组),定量RT-PCR(qRT-PCR)方法验证异常miRNA在ALL患儿骨髓细胞内的表达(qRT-PCR组),结合患儿临床资料分析异常表达的miRNA与ALL预后的关系.[结果]基因芯片结果显示:初发患儿miR-708、miR-181b、miR-199a-3p、miR-320a和miR-145表达上调最为明显,而miR-223、miR-1244、miR-494、miR-124、miR-23a、miR-27a、miR-181a*和miR-23b表达下调最明显;qRT-PCR结果显示:miR-708、miR-223和miR-27a在ALL患儿骨髓细胞内表达与基因芯片结果一致.;无复发生存分析提示ALL初发时高表达miR-708、miR-223、miR-27a者,3年无复发生存率较高,反之预后较差.[结论]miRNA是预测ALL预后的有效分子标记物,初发患儿miR-708、miR-27a和miR-223高表达提示预后良好,在指导临床ALL患儿分层治疗方面具有重要意义.

  13. Relapse or Recurrence

    Science.gov (United States)

    ... possible, upon optimizing the time you have. Your child’s cancer center has a number of resources available to ... Deaths Per Year 5-Year Survival Rate Childhood Cancer Infographics Webinars Parents Webinars Child Life Specialist Webinars School Personnel Webinars Video Library ...

  14. 儿童急性淋巴细胞白血病预防性血小板输注阈值探讨%The threshold analysis for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    周令; 徐学聚; 李欢欢

    2013-01-01

    Objective To investigate the threshold for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia(ALL).Methods To analyze platelet transfusions and bleeding condition during chemotherapy in our department in childhood with ALL.Results 1 10 cases of children with a total 385 cases platelet transfusions.No complication group platelet count < 5 × 109/L,given platelet transfusion,major clinical bleeding events increased,complication group platelet count < 5 × 109/L,the risk of clinical bleeding increased.Conclusions The platelet transfusions threshold of 5 × 109/L for stable ALL patients is safe during chemotherapy.The platelet transfusion trigger was increased to 10 × 109/L or even higher in certain clinical situations.%目的 探讨急性淋巴细胞性白血病患儿化疗过程中预防性血小板输注阈值.方法 分析郑州大学第一附属医院儿科2年间急性淋巴细胞白血病患儿化疗期间血小板输注及出血情况.结果 110例患儿共输注血小板385例次,无合并症组血小板计数<5×109/L时输注血小板,临床主要出血事件增加,有合并症组在血小板计数< 10×109/L时临床出血风险增加.结论 儿童急性淋巴细胞白血病化疗过程中,在患儿一般状态稳定情况下,血小板输注阈值定为5×109/L相对安全,有合并症时血小板输注阈值应为10×109/L或更高.

  15. Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11(q11.2;p15.1 translocation

    Directory of Open Access Journals (Sweden)

    Leszl Anna

    2008-10-01

    Full Text Available Abstract Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11(q11.2;p15.1 translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 (Hermansky Pudlak syndrome 5 intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692. Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation.

  16. 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,

  17. Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.

    Science.gov (United States)

    Aricò, Maurizio; Valsecchi, Maria Grazia; Conter, Valentino; Rizzari, Carmelo; Pession, Andrea; Messina, Chiara; Barisone, Elena; Poggi, Vincenzo; De Rossi, Giulio; Locatelli, Franco; Micalizzi, Maria Concetta; Basso, Giuseppe; Masera, Giuseppe

    2002-07-15

    One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.

  18. 地西他滨联合CAG方案治疗复发难治性急性髓系白血病的临床观察%Clinical outcome of decitabine combined with CAG regimen in the treatment of patients with relapsed refractory acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    于洪霞; 何娟

    2014-01-01

    目的 观察地西他滨联合CAG方案治疗复发难治性急性髓系白血病(AML)患者的临床疗效和不良反应.方法 收集复发难治性AML患者17例,给予地西他滨(25 mg/d,第1天至第5天静脉滴注)联合CAG方案(阿柔比星20mg/d,第3天至第6天静脉滴注,阿糖胞苷10 mg/m2,第3天至第9天1次/12h皮下注射,粒细胞集落刺激因子400 μg/d,第0天至第9天皮下注射).结果 17例患者经过1个疗程地西他滨联合CAG方案治疗后,完全缓解(CR)10例(58.8%),部分缓解(PR)1例(5.9%),未缓解(NR)6例(35.3%),总有效率(ORR)为64.7%(11/17).染色体核型良好组的1例达CR;染色体核型中等组12例中,CR 8例(66.7%),PR 1例(8.3%);染色体核型不良组4例中,CR1例(25.0%),无PR病例,三组ORR比较差异具有统计学意义(P<0.05).随访至2013年1月31日,17例患者中15例生存,2例早期死亡.中位总生存期为67d (14~307d),中位无复发生存期47 d(14 ~ 152 d).结论 地西他滨联合CAG方案治疗复发难治性AML缓解率较高,非血液学不良反应小,耐受性良好.%Objective To discuss the efficacy and safety of decitabine plus aclacinomycin/cytarabine/ G-CSF (CAG) regimen in the treatment of patients with relapsed refractory acute myeloid leukemia (AML).Methods 17 cases with relapsed refractory AML were collected.They were given decitabine (25 mg/d,d1-5) plus CAG regimen (aclacinomycin 20 mg/d,d3-6; cytarabine 10 mg/m2,d3-9; G-CSF 400 μg/d,d0-9).Results After one course treatment by decitabine plus CAG regimen,10 patients (58.8 %) achieved complete response (CR),1 patient (5.9 %) achieved partial response (PR) and 6 patients (35.3 %) displayed no response (NR),the overall response rate was 64.7 % (11/17).For karyotyping of chromosomal abnormalities,only 1 case (100 %) in CR showed normal karyotype.8 cases (66.7 %) in CR,1 case (8.3 %) in PR showed medium karyotype.1 case (25.0 %) in CR showed bad karyotype.Statistical analysis revealed

  19. Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia Detecção de doença residual mínima em crianças com leucemia linfoblástica aguda por citometria de fluxo

    Directory of Open Access Journals (Sweden)

    Elizabete Delbuono

    2008-08-01

    Full Text Available The detection of minimal residual disease (MRD is an important prognostic factor in childhood acute lymphoblastic leukemia (ALL providing crucial information on the response to treatment and risk of relapse. However, the high cost of these techniques restricts their use in countries with limited resources. Thus, we prospectively studied the use of flow cytometry (FC with a simplified 3-color assay and a limited antibody panel to detect MRD in the bone marrow (BM and peripheral blood (PB of children with ALL. BM and PB samples from 40 children with ALL were analyzed on days (d 14 and 28 during induction and in weeks 24-30 of maintenance therapy. Detectable MRD was defined as > 0.01% cells expressing the aberrant immunophenotype as characterized at diagnosis among total events in the sample. A total of 87% of the patients had an aberrant immunophenotype at diagnosis. On d14, 56% of the BM and 43% of the PB samples had detectable MRD. On d28, this decreased to 45% and 31%, respectively. The percentage of cells with the aberrant phenotype was similar in both BM and PB in T-ALL but about 10 times higher in the BM of patients with B-cell-precursor ALL. Moreover, MRD was detected in the BM of patients in complete morphological remission (44% on d14 and 39% on d28. MRD was not significantly associated to gender, age, initial white blood cell count or cell lineage. This FC assay is feasible, affordable and readily applicable to detect MRD in centers with limited resources.A detecção de doença residual mínima (DRM é um importante fator prognóstico na leucemia linfóide aguda (LLA infantil e fornece informações sobre a resposta ao tratamento e o risco de recaída. Entretanto, os altos custos das técnicas utilizadas limitam seu uso nos países em desenvolvimento. Desta forma, realizamos um estudo prospectivo para avaliar a citometria de fluxo (CF, utilizando três fluorescências e um painel limitado de anticorpos monoclonais, como método de detec

  20. FISH检测性染色体在鉴别急性淋巴细胞白血病异基因造血干细胞移植后髓外复发与淋巴细胞增殖性疾病中的临床应用%Identification of acute lymphoctic leukemia extramedullary relapse and PTLD after allo-HSCT by monitoring sex chromosome chimeric status with FISH

    Institute of Scientific and Technical Information of China (English)

    杜璇; 刘启发; 张乐施; 宋兰林; 范志平; 徐兵; 孙竞

    2009-01-01

    目的 探讨荧光原位杂交(fluorescence in situ hybridization,FISH)在鉴别急性淋巴细胞白血病(acute lymphocytic leukemia,ALL)异基因造血干细胞移植(allogeneic hernatopoietic stem celltransplantation,allo-HSCT)后髓外复发与移植后淋巴细胞增殖性疾病(post-transplant lymphoproliferativedisease,PTLD)的可行性.方法 对6例ALL接受性别不同供者HSCT后出现淋巴结肿大或局部包块的患者,用FISH检测患者骨髓或肿瘤组织中性染色体嵌合状态和原位杂交检测肿瘤细胞内EB病毒RNA(Epstein-Barr virus,EBV-RNA).结果 6例患者骨髓细胞性染色体均示100%供者型.肿瘤组织中性染色体嵌合状态:3例受者型分别为100%、100%、98.0%,诊断白血病髓外复发;3例供者型分别为98.5%、96.0%,91.5%,诊断为PTLD.2例供者型患者EBV-RNA和EBV潜伏膜蛋白-1(latent membraneprotein,LMP-1)均阳性,其他患者阴性.经治疗3例髓外复发与3例PTLD患者分别有1例部分缓解,1例完全缓解,另4例患者治疗无效死亡.结论 接受性别不同供者HSCT后出现髓外复发或PTLD的ALlL患者,通过FISH检测患者肿瘤组织中性染色体嵌合状态是鉴别髓外复发与PTLD的十分有效手段.%Objective To explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization (FISH) in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (alIo-HSCT). Methods Six ALL patients who received sex-mismatched alIo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH). Results The sex chromosomes in BM of all 6 patients were 100 % donor-derived. Among the sex chromosome chimeric

  1. 尿中金属元素水平与儿童急性白血病之间的关系%Correlation between level of metallic elements in urine and childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    朱莎; 沈晓明; 张妍; 高宇; 王筱金; 陈涛; 杨友; 施蓉; 金萍; 田英

    2011-01-01

    Objective To explore the relation between the level of metallic elements in urine and childhood acute leukemia. Methods A total of 71 patients under 15 years old who were newly diagnosed with acute leukemia between September 2007 and August 2008 without Downs' syndrome or other tumors,and 113 gender-and age-matched controls without tunors or congenital diseases were enrolled for the case-control study.The general data and potential risk factors were obtained by questionnaires.Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal concentrations in urine,which was collected randomly before chemotherapy.Logistic regression model was performed for univariate and multivariate analysis. Results The questionnaire showed that there was significant difference in the proportion of children whose mothers had taken iron supplements during or 3 months before pregnancy between case group and control group,which was 28.2% (20/71) and 14.2% (16/113) respectively (Wald x2 = 5.438,P =0.02).Univariate logistic regression analysis showed that levels of vanadium,manganese,iron,cobalt,copper,arsenic,and barium in urine from case group were all higher than those of control group with significant difference.The median values for vanadium in urine from case and control groups were 5.39 and 3.04 ng/mg creatinine (Wald x2 = 9.03,P < 0.05);the median values for manganese were respectively 4.46 and 2.44 ng/mg creatinine (Wald x2 = 10.57,P <0.05);the median values for iron were separately 58.69 and 14.09 ng/mg creatinine (Wald x2 = 13.41,P < 0.05);the median values for cobalt were respectively 0.98 and 0.77 ng/mg creatinine (Wald x2 = 4.46,P < 0.05);the median values for copper were 61.17 and 10.90 ng/mg creatinine (Wald x2 = 8.15,P < 0.05);the median values for arsenic were respectively 55.93 and 36.11 ng/mg creatinine (Wald x2 = 4.57,P < 0.05);and the median values for barium were 8.55 and 2.87 ng/mg creatinine (Wald x2 = 4.82,P < 0

  2. 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.

  3. Relapsing Polychondritis Following Alopecia Areata

    Directory of Open Access Journals (Sweden)

    John C. Starr

    2010-01-01

    Full Text Available A case of alopecia areata followed by relapsing polychondritis is presented. Similar cases from the literature are reviewed and speculation about the relationship of these diseases is offered. Although the occurrence of these diseases together could be coincidental, an association seems immunologically plausible. Thus, relapsing polychondritis might be an unusual systemic manifestation of alopecia areata.

  4. Mutations driving CLL and their evolution in progression and relapse

    Science.gov (United States)

    Landau, Dan A.; Tausch, Eugen; Taylor-Weiner, Amaro N; Stewart, Chip; Reiter, Johannes G.; Bahlo, Jasmin; Kluth, Sandra; Bozic, Ivana; Lawrence, Mike; Böttcher, Sebastian; Carter, Scott L.; Cibulskis, Kristian; Mertens, Daniel; Sougnez, Carrie; Rosenberg, Mara; Hess, Julian M.; Edelmann, Jennifer; Kless, Sabrina; Kneba, Michael; Ritgen, Matthias; Fink, Anna; Fischer, Kirsten; Gabriel, Stacey; Lander, Eric; Nowak, Martin A.; Döhner, Hartmut; Hallek, Michael; Neuberg, Donna; Getz, Gad; Stilgenbauer, Stephan; Wu, Catherine J.

    2015-01-01

    SUMMARY Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. We identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized cancer drivers (RPS15, IKZF3) and collectively identify RNA processing and export, MYC activity and MAPK signaling as central pathways involved in CLL. Clonality analysis of this large dataset further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing datasets of clinically informative samples enable the discovery of novel cancer genes and the network of relationships between the driver events and their impact on disease relapse and clinical outcome. PMID:26466571

  5. Childhood myelodysplas