T he FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia (AML). Because of the poor prognosis associated with FLT3-internal tandem duplication mutated AML, allogeneic hematopoietic stem-cell transplantation (SCT) was commonly performed in first complete remission. Remarkable progress

With standard chemotherapy regimens for adults with acute lymphoblastic leukemia, approximately 90% of patients achieve complete remission. However, up to half of patients have persistent minimal/measurable residual disease (MRD) not recognized by routine microscopy, which constitutes the leading determinant of relapse. Many studies in pediatric and adult populations have demonstrated that achievement of MRD negativity after induction chemotherapy or during consolidation is associated with significantly better long-term outcomes, and MRD status constitutes an independently prognostic marker, often superseding other conventional risk factors. Persistence of MRD after intensive chemotherapy is indicative of treatment refractoriness and warrants alternative therapeutic approaches including allogeneic stem cell transplantation, blinatumomab, or investigational therapies such as inotuzumab ozogamicin or chimeric antigen receptor T cells. Furthermore, the incorporation of novel monoclonal antibodies or potent BCR-ABL1 tyrosine kinase inhibitors, such as ponatinib into frontline treatment may have the advantage of achieving higher rates of MRD negativity while minimizing chemotherapy-related toxicities. Many studies are therefore ongoing to determine whether this strategy can improve cure rates without the need for allogeneic stem cell transplantation.

Purpose: Relapsed acute myeloid leukemia (AML) post allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis.Experimental Design: To assess prognosis of patients with recurrent AML post allo-HCT over time, we analyzed European Society for Blood and Marrow Transplantation registry data of 8,162 adult patients with AML who relapsed between 2000 and 2018 after allo-HCT performed in first complete remission from matched sibling, unrelated, or haploidentical donors.Results: The 2-year overall survival (OS) rate from relapse was 17%. For 3,630 patients, <50 years of age, the 2-year OS continuously increased from 16% between 2000 and 2004 to 18% for 2005-2009, to 21% for 2010-2014, and to 26% for 2015-2018 (P ¼ 0.001). Improvement over time was noted both after relapse within and beyond 6 months from allo-HCT. On multivariate analysis among patients <50 years of age, OS was positively affected by a later year of relapse (baseline: 2000-2004; HR, 0.82; P < 0.02 for 2010-2014 and HR, 0.72; P ¼ 0.0002 for 2015-2018), good performance status, favorable cytogenetics, and longer time from transplant to relapse, but negatively affected by increasing age. In contrast, among 4,532 patients, >50 years of age, the year of relapse had no influence on OS (16% for 2000-2004 and 14% for 2015-2018; P ¼ 0.56). Regarding treatment, encouraging results were observed after second allo-HCT, which was performed within 2 years after relapse in 17% of the entire cohort, resulting in a 2-year OS of 30.7%.Conclusions: Outcome after posttransplant relapse among younger patients has improved significantly in recent years, likely reflecting, among other factors, the efficacy of posttransplant salvage including second allo-HCT.

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