Abstract：Objective To evaluate the effectiveness and the practicability of the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 95 (ALL-BFM 95) protocol in treating childhood high-risk acute lymphoblastic leukemia (HR-ALL). Methods A retrospective analysis of 47 children with newly diagnosed HR-ALL between July 2003 and August 2013 was performed. These children were treated by the ALL-BFM 95 protocol. Survival was evaluated by Kaplan Meier analysis and Log-Rank test. Results Relapse-related death occurred in 12 of 47 patients (26%), and 5 of 47 patients (11%) were treatment-related mortality. Five-year probability of event-free-survival (pEFS) was 62%. Children with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than those with chemotherapy alone (77% vs 52%; P=0.035). The patients who were only poor responders to prednisone had a better outcome (5-year pEFS 80%) than the Days 15 and 33 bone marrow M3 subgroups (5- year pEFS 60% and 0 respectively). Conclusions ALL-BFM 95 protocol can improve the outcome of children with high-risk ALL. The major cause of death is attributed to relapse. Chemotherapy plus HSCT can produce a better outcome than chemotherapy alone. The Days 15 and 33 bone marrow M3 subgroups have a poor prognosis.
Gaynon PS, Angiolillo AL, Carroll WL, et al. Long-term results of the children's cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: a Children's Oncology Group Report[J]. Leukemia, 2010, 24(2): 285-297.
[2]
Moricke A, Zimmermann M, Reiter A, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981- 2000[J]. Leukemia, 2010, 24(2): 265-284.
[3]
Moricke A, Reiter A, Zimmermann M, et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95[J]. Blood, 2008, 111(9): 4477-4489.
Uckun FM, Nachman JB, Sather HN, et al. Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: a report from the Children’s Cancer Group[J]. Cancer, 1998, 83(9): 2030-2039.
[6]
Arico M, Valsecchi MG, Camitta B, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia[J]. N Engl J Med, 2000, 342(14): 998- 1006.
[7]
Schultz KR, Carroll A, Heerema NA, et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children’s Oncology Group Study AALL0031[J]. Leukemia, 2014, 28(7): 1467-1471.
Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of high-risk acute lymphoblastic leukaemia[J]. Lancet Oncol, 2009, 10(2): 147-156.
[10]
Lauten M, Moricke A, Beier R, et al. Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia[J]. Haematologica, 2012, 97(7): 1048-1056.
[11]
Schrappe M, Reiter A, Ludwig WD, et al. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radio-therapy: results of trial ALLBFM 90. German-Austrian-Swiss ALL-BFM Study Group[J]. Blood, 2000, 95(11): 3310-3322.
[12]
Conter V, Valsecchi MG, Parasole R, et al. Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study[J]. Blood, 2014, 123(10): 1470-1478.
[13]
Schrappe M, Hunger SP, Pui CH, et al. Outcomes after induction failure in childhood acute lymphoblastic leukemia[J]. N Engl J Med, 2012, 366(15): 1371-1381.
[14]
Flohr T, Schrauder A, Cazzaniga G, et al. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOPBFM ALL 2000 for childhood acute lymphoblastic leukemia[J]. Leukemia, 2008, 22(4): 771-782.
[15]
Balduzzi A, Valsecchi MG, Uderzo C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study[J]. Lancet, 2005, 366(9486): 635-642.
[16]
Pulsipher MA, Peters C, Pui CH. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant?[J]. Biol Blood Marrow Transplant, 2011, 17(1 Suppl): S137-S148.
[17]
Leung W, Campana D, Yang J, et al. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia[J]. Blood, 2011, 118(2): 223-230.
