Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005-2011 – experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)

Abstract

Aim of the studyRecent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005–2011.Material and methodsThe outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children.ResultsSeventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1.ConclusionsThe uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience

“…Interestingly, two prospective studies documented no survivors among patients with active disease at SCT, but only 13 such cases between both studies were reported, making any further comparison difficult. 4,14 The available literature does not support specific transplant strategies for these patients in terms of conditioning regimens, donor choices, stem cell sources. The size of our cohort precludes definitive evaluations but our data suggest that MAC may improve outcomes compared with reduced intensity conditioning (5 years LFS 50% vs 20%, Po 0.05).…”

“…Different approaches and non-uniform cohorts have yielded widely varying results, with survival rates of 0-35% and transplant-related mortality (TRM) as high as 40%. 4,9,[8][9][10][11][12][13][14] Specifically, for children not in remission at transplant, a total of 160 patients have been reported in four different papers. 4,8,10,14 Three of these papers (including two prospective national studies) document a 0% long-term OS for children with active disease at SCT.…”

“…4,9,[8][9][10][11][12][13][14] Specifically, for children not in remission at transplant, a total of 160 patients have been reported in four different papers. 4,8,10,14 Three of these papers (including two prospective national studies) document a 0% long-term OS for children with active disease at SCT. 4,10,14 On the contrary, Bunin et al 8 documented a leukemiafree survival (LFS) of 12% for children with primary refractory AML and of 20% for relapsed refractory patients.…”

“…4,8,10,14 Three of these papers (including two prospective national studies) document a 0% long-term OS for children with active disease at SCT. 4,10,14 On the contrary, Bunin et al 8 documented a leukemiafree survival (LFS) of 12% for children with primary refractory AML and of 20% for relapsed refractory patients. Moreover, in a registry analysis combining data from adults and children by the CIBMTR on 1428 AML patients in non-remission at transplant, 19% OS has been reported.…”

Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial

“…There are few studies reporting in detail clinical features and treatment outcome of paediatric patients with primary resistant AML. Due to small numbers, these children are often incorporated into cohorts of relapsed or poor responder AML patients (Bunin et al, 2008;Goemans et al, 2008;Gorman et al, 2010;Skalska-Sadowska et al, 2014).…”