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

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.

Smart Conditioning with Venetoclax-Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies

“…These observations are in line with the analyses of Platte et al, who found cytogenetics, disease risk stratification at diagnosis, and pretransplant strategies to be major determinants for the time of relapse. [37]. Our data regarding timely reconstitution of neutrophils and platelets, rate of acute and chronic GVHD, no additional extra hematologic toxicity, as well as early response and relapse are in line with the results of Garcia et al, who added venetoclax to fludarabin/busulfan and evaluated the combination as feasible and safe [21].…”

Smart Conditioning with Venetoclax Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies

“…These observations are in line with the analyses of Platte et al, who found cytogenetics, disease risk stratification at diagnosis and pretransplant strategies to be major determinants for the time of relapse. [39]. Our data regarding timely reconstitution of neutrophils and platelets, rate of acute and chronic GVHD, no additional extra hematologic toxicity as well as early response and relapse are in line with the results of Garcia et al who added Venetoclax to Fludarabin/Busulfan and evaluated the combination as feasible and safe [22].…”