Early Intensification Therapy in High-Risk Childhood Acute Lymphocytic Leukemia: Lack of Benefit from High-Dose Methotrexate

Janka, Gritta; Winkler, Karl; Juêrgens, H.; Goebel, Ulrich; Groups, Coall Study

doi:10.1007/978-3-642-71213-5_80

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…Detailed information of the COALL studies has been given previously. [1][2][3][4][5] In study COALL-82 (1982COALL-82 ( -1985, for the subgroup of patients defined as low risk by an initial WBC Ͻ25 × 10 9 /l and immunological subtype common-ALL a reduction of treatment intensity was performed. During intensive phase, consisting in COALL-80 of cyclophosphamide (CYC), three blocks of cytarabine (ARA-C) and 6-MP, CYC was replaced by intermediatedose methotrexate (MTX) and no reinduction therapy was given.…”

Section: Methodsmentioning

confidence: 99%

Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92

2000

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Co-operative study group for childhood acute lymphoblastic leukemia (COALL): longterm follow-up of trials 82, 85, 89 and 92DO Harms, GE Janka-Schaub on behalf of the COALL Study Group Children's University Hospital, Department of Hematology and Oncology, Hamburg, GermanyThe German Co-operative Study Group COALL for treatment of acute lymphoblastic leukemia (ALL) in childhood started the first trial in 1980. This report gives an overview of the long-term results of the four consecutive studies COALL-82, COALL-85, COALL-89 and COALL-92. Besides improvement in long-term survival major objectives were reduction of treatment-related toxicity by transferring asparaginase (ASP) from induction therapy to intensive phase and omitting CNS irradiation by stepwise increase of the initial white blood count (WBC) up to 50 × 10 9 /l (exception T-ALL) as criterion for irradiation. In study COALL-85 in high risk patients slow vs rapid rotational treatment was randomized. In study COALL-92 initial response to daunorubicin (DNR) as a 1-h vs 24-h infusion and its prognostic value was investigated. Furthermore, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were randomized in maintenance treatment. In total, 1191 eligible patients were enrolled. Induction treatment without ASP has been shown to be as effective and less hazardous than the former four-drug induction. CNS control could be obtained in most without cranial irradiation (CNS relapse-free survival Ͼ95%). The leukemic cell kill with a 24-h DNR infusion was equivalent to that of a 1-h infusion. DNR response was of less prognostic significance than prednisone response. The rapid rotation regimen failed to improve outcome as well as 6-TG in maintenance treatment. However, intensification of systemic treatment resulted in an increase in overall event-free survival (EFS) to approximately 80% which is comparable to other groups. Leukemia (2000) 14, 2234-2239.

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Section: Methodsmentioning

confidence: 99%

Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92

2000

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“…There were no major modifications in the treatment backbone compared with the predecessor CoALL 06-97 trial, including the treatment reductions in patients with excellent in vitro response. 3,[18][19][20][21] However, the cumulative amount of intrathecal methotrexate (IT-MTX) was reduced in CoALL 07-03 from 18 to 14 doses, and pegylated asparaginase replaced the native E coli-derived asparaginase, not only in case of allergic reactions toward asparaginase but for all patients from the third dose onward. All patients received the same 3drug induction (supplemental Figure 1), including a randomized prephase comparing the kinetics of blast counts after a single dose of daunorubicin vs doxorubicin.…”

Section: Treatmentmentioning

confidence: 99%

Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity

et al. 2019

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“…The aim of the first three trials was to define risk criteria of acute lymphoblastic leukaemia (ALL) of childhood by combining the first known risk factor, initial white blood cell count (WBC), with the variables age at diagnosis, immunophenotype and chromosomal rearrangements to establish and optimize a risk-adapted treatment approach. [1][2][3] In COALL 92, the in vitro drug sensitivity, which was determined using the methyl-thiazol-tetrazolium assay, was prospectively evaluated and implemented in COALL 97 as a new risk variable. 4 COALL 92 also focussed on the mode of administration of anthracyclines and on the drug of choice in maintenance therapy.…”

Section: Introductionmentioning

confidence: 99%

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

et al. 2009

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In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P ¼ 0.001). Through all COALL studies, age X10 years and initial white blood cell count (WBC) X50 Â 10 9 /l and pro-B immunophenotype were of significant prognostic relevance. A refinement of risk assessment has been achieved by in vitro drug sensitivity testing in COALL 92 and 97. In patients with very sensitive leukaemic cells, therapy could be reduced without loss of efficacy. In COALL 97, a further improvement in risk stratification was gained by the molecular assessment of minimal residual disease (MRD) under treatment, which proved to have a superior prognostic effect when compared with in vitro drug sensitivity testing. Importantly, the gradual reduction in central nervous system (CNS) irradiation led to a decreased incidence of brain tumours as a second malignancy. In general, the prevention of treatmentrelated late effects will be one of the major issues in future studies. It remains to be shown whether prolonged infusions of anthracyclines, which have been implemented into the COALL studies after equal efficacy compared with short-time infusions was confirmed, will be associated with fewer cardiac late effects. Another way to prevent late effects may be a more refined risk assessment allowing for a reduction in cumulative treatment burden. A great challenge in the future will be to improve the overall treatment results, which very likely can only be achieved by the identification of molecularly defined subgroups to which novel, rational therapeutic strategies can be applied.

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Early Intensification Therapy in High-Risk Childhood Acute Lymphocytic Leukemia: Lack of Benefit from High-Dose Methotrexate

Cited by 6 publications

References 7 publications

Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92

Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92

Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97

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