Pediatric relapsed acute myeloid leukemia: a systematic review

Abstract

Introduction: Pediatric relapsed acute myeloid leukemia (AML) remains lethal in the majority of cases, despite intensive therapy. Randomized trials are largely lacking, and the main issues of optimal therapy and prognostic factors remain unclear. Area covered: This systematic review includes all literature evaluating treatment outcome after first relapse. We searched databases PubMed and Embase.com. Twelve out of six thousand articles were ultimately included, based on age of the population (<21 years), relapsed AML, and information on clinical outcome (second complete remission (CR2), disease-free survival (DFS), event-free survival (EFS) and overall survival (OS)). There was only one randomized clinical trial reported. This review shows that there is no standard treatment for relapsed AML in children, and that outcome varies for CR2 and (2-to 10-year) OS rates, mean 64% (range, 50-75%), and 31% (16-43%), respectively. Children treated with chemotherapy only in first complete remission (CR1) tend to have better outcome after relapse than children receiving allo-SCT in CR1. Allo-SCT seems to be the most effective consolidation therapy in children achieving CR2, after relapse. Duration of CR1 was the most frequently reported statistically significant prognostic factor. Through randomized clinical trials, better knowledge of prognostic factors enabling risk-stratified treatment, and of more effective and less toxic therapies, should contribute to better clinical outcome for children with relapsed AML. Expert opinion: Outcome of pediatric relapsed AML has improved to OS rates up to 40%. However, there is a lack of knowledge on (independent) prognostic factors, optimal reinduction chemotherapy, timing of allo-SCT, and late effects. International collaboration should enable large, randomized clinical trials addressing these issues.

Outcome of pediatric acute myeloid leukemia (AML) in low- and middle-income countries: a systematic review of the literature

“…Finally, the inferior treatment outcomes can be attributed to the low salvage rates after relapse. Although current relapse rates in HICs also reach up to 25-30% [8] with pOS for these patients at about 40% [59], LMICs often lack possibilities in offering optimal salvage therapy, including allo-SCT. Hence, the salvage rate after relapse in LMICs is very low, which is also reflected in the subtle differences between pEFS and pOS.…”

Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG

“…There has been considerable improvement in overall probability of survival (pOS) for patients in first relapse since 1987, improving from a 5-year-pOS of 21–23% in the 1980s and 1990s [ 11 , 12 , 13 ] to 36–39% in patients’ relapse prior to 2014 [ 9 , 14 , 15 , 16 ]. Studies consistently demonstrate that duration of first remission (CR1), age at relapse (less than ten years), favorable cytogenetics such as core binding factor (CBF) AML and good treatment response after re-induction therapy predict a more favorable outcome [ 9 , 10 , 11 , 12 , 13 , 14 , 17 , 18 , 19 , 20 , 21 ].…”

Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group

“…Since 1987, international reports of survival after first relapse demonstrate a considerable improvement in overall survival for patients in first relapse. The five-year probability of overall survival (pOS) after relapse was 21–24% for patients between 1987 and 1997 [ 13 , 14 , 15 ], improving to 37–39% in recent studies through 2014 [ 10 , 16 , 17 , 18 , 19 ].…”