Clinical and Cytogenetic Characterization of Early and Late Relapses in Patients Allografted for Myeloid Neoplasms with a Myelodysplastic Component

SIMPLE SUMMARY: Relapse as the most common reason for treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-SCT) in myeloid neoplasms usually occurs during the first year post-transplant, but several patients experience late relapse. This retrospective study aimed to characterize early and late relapses regarding clinical and cytogenetic parameters. Analyzing 91 consecutive patients, we demonstrated an improved overall survival for late compared with early relapsed patients and carved out cytogenetics and disease risk stratification at diagnosis as well as pretransplant strategy as major determinants for the timepoint of relapse. The impact of cytogenetics was highlighted by comparative karyotype analyses demonstrating a higher frequency of clonal evolution in early relapses. Improving knowledge about factors predicting early relapse may enable a selection of patients who may benefit from strategies to prevent or delay relapse, and identifying patients being at risk for late relapse may trigger prolonged surveillance strategies, including bone marrow biopsies and measurable residual disease (MRD) assessment. ABSTRACT: An improved understanding of relapse kinetics is required to optimize detection and treatment strategies for the post-transplant relapse of myeloid neoplasms. Therefore, we retrospectively analyzed data from 91 patients allografted for MDS (n = 54), AML-MRC (n = 29) and chronic myelomonocytic leukemia (CMML, n = 8), who relapsed after transplant. Patients with early (<12 months, n = 56) and late relapse (>12 months, n = 35) were compared regarding patient-, disease- and transplant-related factors, including karyotype analyses at diagnosis and relapse. After a median follow-up of 17.4 months after relapse, late relapses showed improved outcomes compared with early relapses (2-yr OS 67% vs. 32%, p = 0.0048). Comparing frequency of distinct patient-, disease- and transplant-related factors among early and late relapses, complex karyotype (p = 0.0004) and unfavorable disease risk at diagnosis (p = 0.0008) as well as clonal evolution at relapse (p = 0.03) were more common in early than in late relapses. Furthermore, patients receiving transplant without prior cytoreduction or in complete remission were more frequently present in the group of late relapses. These data suggest that cytogenetics rather than disease burden at diagnosis and transplant-related factors determine the timepoint of post-transplant relapse and that upfront transplantation may be favored in order to delay relapse.