• C Craddock, J Versluis, M Labopin, G Socie, A Huynh, E Deconinck, L Volin, N Milpied, J H Bourhis, A Rambaldi, P Chevallier, D Blaise, M Manz, E Vellenga, M-C Vekemans, J Maertens, J Passweg, P Vyas, C Schmid, B Löwenberg, G Ossenkoppele, M Mohty, J J Cornelissen, A Nagler, and Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and HOVON-SAKK.
• Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.
• J. Intern. Med. 2018 Apr 1; 283 (4): 371-379.

BackgroundDisease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT).AimsThe timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized.Materials And MethodsWe have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone.ResultsIn the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012).Discussion And ConclusionTaken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.© 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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