Outcome of Relapsed Acute Myeloid Leukemia (AML) in Children According to Duration of First Complete Remission

Abstract

Between a third and a half of children treated for acute myeloid leukaemia relapse, and the length of the first remission has long been the variable clinicians reach for when estimating what salvage can achieve. It does predict outcome. What the larger studies show is that it is no longer the best available predictor. Objectives: To review the published evidence on outcome after first relapse of paediatric acute myeloid leukaemia stratified by duration of first complete remission: how the early and late thresholds were derived, what each predicts for second remission and survival, and how the measure compares with response to reinduction. Material and Methods: Narrative review of cooperative group relapse trials, registry analyses and single-institution cohorts indexed in PubMed and the major haematology and paediatric oncology journals. Studies were eligible if they reported outcome after relapse of paediatric acute myeloid leukaemia stratified by remission duration or by response to salvage. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: In the largest international relapse trial, second complete remission was achieved in 62 to 63 per cent of patients after two courses of fludarabine-based
reinduction. Two-year survival was 38 per cent (SE 9) for early relapse against 54 per cent (SE 7) for late relapse, with 33 per cent (SE 5) for the cohort as a whole. Achieving second remission was the dominant determinant: three-year survival was 47 per cent in those who did against 8 per cent in those who did not. Across the wider literature, three to five-year survival is 10 to 28 per cent after relapse within 12 to 18 months and 40 to 48 per cent thereafter. Response to reinduction stratified more finely than timing: marrow blasts at day 28 of 5 per cent or less, 6 to 10, 11 to 20 and above 20 per cent corresponded to four-year survival of 52, 36, 21 and 14 per cent (p < 0.0001), while day 15 status showed no such gradient. Conclusion: Remission duration is a genuine prognostic factor and an unmodifiable one, known before any salvage decision is taken. Response at day 28 after reinduction separates outcomes across a wider range and is measured at the point where treatment can still change, which makes it the more useful of the two.
Abbreviations: AML – Acute Myeloid Leukaemia, CR1 – First Complete Remission, CR2 – Second Complete Remission, FLAG – Fludarabine, Cytarabine and Granulocyte Colony-Stimulating Factor, HSCT – Haematopoietic Stem Cell Transplantation, BFM – Berlin-Frankfurt-Münster, COG – Children’s Oncology Group, OS – Overall Survival, EFS – Event-Free Survival, pSurv – Probability of Survival, SE – Standard Error, MRD – Measurable Residual Disease.