Risk Factors for Survival in Children with Refractory AML Treated According to AML Relapse Strategies
About one third of the children treated within the national studies for AML in Germany (BFM studies) experience recurrence of their disease. In order to estimate the value of intensive salvage therapy for children with AML, we analysed the relapse regimens of the BFM study group for outcome and risk factors.
Patients and Treatment. 102 patients (pts.) with first relapse of AML were treated according to BFM relapse strategies: study REZ91 with double induction (mitoxantrone [MITOX]/VP-16 twice, 15 pts.), study REZ93 with induction MITOX/VP-16 plus HD-Ara-C/MITOX (HAM, 28 pts.) followed by a 6-week consolidation and either allogeneic or autologous bone marrow transplantation (BMT). Another 59 patients received either elements of these protocols or other intensive salvage therapy.
Results. Time to relapse was in median 1.1 years, range 0–15 years. Fifty-two of 102 patients (51%) achieved 2nd remission (CR), 10 (10%) partial remission, 37 (36%) were nonresponders, and 3 (3%) died early during salvage therapy. Twenty-seven were alive, in median 2.5 years, range 0.4–7.0 years after relapse, overall survival was 21%, SE 5% after 5 years. The response and survival rate was similar in all treatment groups. MITOX/VP16 induction was well tolerated: 6 of 26 patients in study REZ93 suffered severe infections after 1st induction, compared to 9 of 12 patients after HAM. Fifty patients were transplanted, 43 in 2nd CR, and 7 with residual blasts; 27 patients received an allograft: Twenty-one from a matched sibling (MSD), 1 from a haploid and 5 from a matched unrelated donor (MUD); 23 received an autograft. Results were poor for patients in partial remission, however, promising for autologous BMT in 2nd CR with 10 of 22 patients surviving. Seven of 16 were alive after MSD in 2nd CR and 1 after haploid BMT, 4 of 5 patients died after MUD BMT. Multivariate risk factor analysis for survival after relapse revealed duration until relapse to be the most important factor. The maximum risk-ratio was obtained with a threshhold value of 1.5 years after diagnosis resulting in a 5-year survival of 10%, SE 4% for early relapse, and 40%, SE 10% for late relapse,p logrank 0.0001.
Conclusion. Second CR can be achieved in half of the patients, however, only children with late relapse (>1.5 years after diagnosis) have a realistic chance to be cured.
KeywordsAcute Myeloid Leukemia Acute Myelogenous Leukemia Autologous Bone Marrow Transplantation Late Relapse Matched Unrelated Donor
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