This treatment differs from the all icbfm 2002 protocol as follows. The multicentre prospective randomized study allrez bfm 2002 was designed to compare the efficacy and toxicity of rcourses and protocol iiidarubicin prot iiida as postinduction therapy in children with relapsed all. The previous study allic bfm 2002, which, compared with other international studies, achieved a high percentage of first. Current approach to relapsed acute lymphoblastic leukemia. All rez bfm 2002 pdf we categorized the relapse treatment into four groups. Get information about risk factors, signs, diagnosis, molecular features, survival, riskbased treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent all. Purpose from 2002 to 2007, the international berlinfrankfurtmunster study group conducted a prospective randomized clinical trial all ic bfm 2002 for the management of childhood acute lymphoblastic leukemia all in 15 countries on three continents.
The longterm outcome of 90 children with acute lymphoblastic leukemia all, treated in two successive clinical trials taiwan pediatric oncology group tpogall97 and tpoga. Within the group, over the last few years two different treatment protocols, allrez bfm 2002 and all r3 have been used by most study groups for treatment of relapsed all. Acute lymphoblastic leukaemia bfm 2000 treatment overview. Current treatment approaches in childhood acute lymphoblastic leukemia martin schrappe, martin stanulla abstract acute lymphoblastic leukemia all is the most common malignancy of childhood and has served as a model system for clinical and basic research beyond pediatric hematooncology since the early 1960s. Fiveyear eventfree survival rates are 93 percent for lowrisk groups.
Munster bfm all protocols the bfm study group is conducting an international clinical trial aieop. Risk classification was based on age, white blood cell count, immunophenotype, genetics when available, and early response to therapy. Riskadapted stratification and treatment of childhood all. Twelve patients in the pegasnase group had no recorded prior exposure to any asnase, 7 of which had undetectable asnase activity. All risk groups prednisolone po 60 mgm2 day 1 to 28 then taperover10 daysandcease methotrexate it 12 mg days 1, 12, 33. Thromboembolic events in children with acute lymphoblastic. If minimal residual disease mrd testing is available, then the incorporation of these results appears justified on the published data, at least for the preb all group. The study is based on the results of five consecutive trials performed by the allrez bfm study group since 1983.
Besides these clinical prognostic factors, molecular markers have been found to be associated with survival after relapse. Chromosomal aberrations in childhood acute lymphoblastic. Treatment of childhood acute lymphoblastic leukemia. The treatment of childhood acute lymphoblastic leukemia in. All bfm rez 2002 study had received up to 6 previous doses of pegasnase. Survival rates for alllbl have improved dramatically since the 1980s, with current fiveyear overall survival rates 85 percent. Outcomes of patients with childhood bcell precursor acute. The all ic bfm 2002 protocol was created as an alternative to the mrdbased aieop bfm all 2000 study, to integrate early response criteria into riskgroup stratification in countries not. The trials risk stratified patients based on duration of first.
The characteristics of the patients treated with the successive all bfm 90, all bfm 95 and all ic bfm 2002 protocols are depicted in table 1distribution of patients according to the major clinical features did not differ significantly among the respective trials. With parental consent, children 12 months of age and older who had acute onset of all treated according to the bfm 9095 or the bfm 2000 induction protocols between december 1994 and january 2002 were included in this prospective multicenter analysis. Study protocol short version short title gmall 072003 full study title multicenter study to optimize treatment of acute lymphoblastic leukemia in adults 15 years treatment optimization by evaluation of minimal residual disease. Bfmoriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment. For acute lymphoblastic leukemia all, the 5year survival rate has improved significantly since 1975. Outline of induction see reference below for diagram. All ic bfm 2002 may 2002 1 all ic bfm 2002 a randomized trial of the i bfm sg for the management of childhood nonb acute lymphoblastic leukemia final version of therapy protocol from may 3, 2002 start 01. Intensive chemotherapy for childhood acute lymphoblastic. The primary objective of study allrez bfm 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Assessment of hematological toxicity in children with. The protocol allrez bfm 2002 aims at the optimization of treatment for children with relapsed acute lymphoblastic leukemia.
Allicbfm 2002 protocol in the institute of hematology and inmunology. The all bfm 2000 standard arm has been used as the treatment regimen in this protocol, since it is common to both allbfm95 and all bfm 2000 regimens. The new study protocol allic bfm 2009 is the final result of very comprehensive data analyses and discussions over the last few years. Childhood acute lymphoblastic leukemia treatment pdq. Clinical research performed within the allic bfm group but also in parallel in the context of trial aieop bfm. Among patients who were uniformly treated by the allrez bfm 2002 protocol for relapsed disease, deletion of ikzf1 and. Clinical research performed within the allic bfm group but also in parallel in the context of trial aieop bfm all 2000 produced. The bfm chemotherapy regimen has been a standard treatment for pediatric all, with promising outcomes in terms of remission and longterm survival. In a prospective and blinded study, the allrez bfm study group evaluated the impact of pretransplantation mrd in children treated according to the allrez bfm 96 or 2002 protocol who received their transplantation in cr2 or third cr cr3. The aml bfm 2004 trial is an multicenter doseoptimization trial for the treatment of acute myeloid leukeamias in children and adolescents. Patients with bcell precursor acute lymphoblastic leukaemia with late bone marrow relapses and low minimal residual disease at end of induction had favourable outcomes with chemotherapy without undergoing stemcell transplantation. Patients are treatetd with a combination of intensive chemotherapy in combination with a radiation of the central nervous system stopped with the amendment of april 2010 and or haematopoietic stem cell.
This concept drove the design of the all icbfm 2002 trial to be conducted in. After the substantial improvements in cure rates for childhood acute lymphoblastic leukemia all obtained with intensified treatment strategies in the 1970s and 1980s, the last decade has seen slower progress on several fronts. In sr, protocol iii was repeated twice 12 weeks apart in the. Pdf intensive chemotherapy for childhood acute lymphoblastic. All bfm aieop all2000 relapsed all all rez bf m2002 dclsg all9 interfant 99 mrcall 9799 ukallr3 coall0697 fralle 2000 eortcclg 58951 nopho all2000 prebmt all adult all gmall 0699 adult all lala 2000 adult all ukall xii adult all pethema geth by. Minimal residual diseasedirected risk stratification using realtime quantitative pcr analysis of immunoglobulin and tcell receptor gene rearrangements in the international multicenter trial aieop bfm all 2000 for childhood acute lymphoblastic leukemia. Bfm all 2000 for childhood acute lymphoblastic leukemia. Acute lymphoblastic leukemialymphoma alllbl is the most common form of cancer in children, comprising approximately 30 percent of all childhood malignancies. It is designed as a prospective controlled randomized multicenter study. Rez bfm 2002 by nov 2010, 830 relapses were registered.
The aim of this trial was to explore the impact of differential delayed intensification di on outcome in all risk groups. Three relapsed patients were excluded, due to they were treated with a different protocol all rez bfm 2002 and 3 children with. Risk group stratification and therapy elements of the treatment protocols have been described in detail elsewhere 15, 16, 17, 18. Cortes j, thomas d, rios a, koller c, obrien s, jeha s, faderl s. Diagnosis of all was based on standard morphologic, cytochemical, immunophenotype and genetic studies. The treatment of childhood acute lymphoblastic leukemia. Nine patients in the pegasnase group were enrolled in the all bfm rez 2002 study, and 19 patients were enrolled in the all bfm 2000 study. Clinical significance of minimal residual disease at the. Burkitts acute lymphoblastic leukemia l3all in adults.
Allicbfm 2002 protocol in the institute of hematology and. In 2007, an amendment to the intercontinental bfm 2002 protocol was defined as more suitable for the diagnosis and treatment of children with all in colombia. The results are remarcable the remission at tp2 was in 97,3% and remained in remission until present. Antibody against polyethylene glycol adversely affects. Longterm followup has revealed late treatmentrelated adverse effects and focused attention on risktargeted therapy to minimize adverse effects in patients. Coclussion our patients had favourable outcome following all bfm 2002 protocol, at tp1 88,6% obtained molecular remission. Treatment outline and randomized questions in all ic bfm 2002 acute lymphoblastic leukemia intercontinental berlinfrankfurtmu.
The characteristics of the patients treated with the successive all bfm 90, all bfm 95 and all ic bfm 2002 protocols are depicted in table 1distribution of patients according to the major. P191 evaluation of minimum residual disease in paediatric. International collaborative treatment protocol for. Therefore, in 2003, the all bfm and the allrelapse rez bfm study groups initiated a prospective, international, multicenter protocol allsct bfm 2003, which will now be extended to a larger international consortium. Patients were treated based on the intermediaterisk arm of allic bfm 2002 protocol consisted of induction protocol i, consolidation protocol m, delayed intensification protocol ii and maintenance therapy with a total duration of 2 years. Intensive chemotherapy for childhood acute lymphoblastic leukemia. Radtke h, schwamborn j, graf n 1992 the bfm protocol for hivnegative burkitts lymphomas and l3 all in adult patients.
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