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• W2912278056 abstract "BackgroundRelapse continues to be the major cause of death in AML/MDS patients following allogeneic hematopoietic cell transplantation (HCT). Advanced age has emerged as a strong predictor of relapse due to both generally increased disease risk and reduced ability to deliver myeloablative conditioning due to comorbidities and functional impairment. The impact of measurable residual disease (MRD) prior to HCT has not been assessed in the context of older patients receiving CD34+ selected allografts.MethodsWe retrospectively examined 297 AML/MDS patients aged 60 years and older who underwent first allo-HCT at our institution from 2001 to 2016. We included only patients who received either a conventional or CD34+ selected graft. We collected MRD data using flow cytometry, cytogenetics (karyotype and/or FISH), and molecular mutation analysis from patients who had achieved a hematologic complete remission pre-HCT. Factors associated with the cumulative incidence of relapse (RI) and progression-free survival (PFS) were analyzed using cause-specific hazard models.ResultsThe median age was 65.8 years (range 60-78.4), and 42% were women. One hundred and eighty-four patients had AML (62%). Fifty-nine percent of patients had HCT-CI >2; 51% had pre-HCT KPS >80; and 37% had high/very high disease risk index (DRI). Seventy-five percent of patients received a myeloablative regimen and 61% received a CD34+ selected graft. Sixteen percent of patients had a mismatched donor. With a median follow-up of 5.1 year for survivors, the 2- and 5-year overall survival was 50% (95% CI: 44-55) and 39% (95% CI: 33-45) respectively. The 2- and 5-year of PFS was 46% (95% CI: 40-51) and 37% (95% CI: 31-43) respectively. By June 30, 2018, 93 patients had relapsed, or their disease progressed, with 3-year cumulative RI of 31% (95% CI: 26-36). Two hundred and four patients had available MRD data and 71, 35%, were MRD positive pre-HCT. In multivariate analysis of RI (Table below), high/very high DRI score (HR 2.2, 95% CI: 1.3-3.8, p=0.004) and MRD positivity (HR 1.9, 95% CI: 1.1-3.2, p=0.027) were associated with an increased risk, with CD34+ selection approaching statistical significance for a reduced risk (HR 0.6, 95% CI: 0.3-1, p=0.064). In multivariate analysis of PFS, only high/very high DRI score (HR 1.8, 95% CI: 1.2-2.7, p=0.003) was associated with an increased risk.ConclusionsIn this study, we characterized relapse following allogeneic HCT in an older cohort of AML/MDS patients. While limited by the retrospective nature with likely underestimation of MRD status due to different assays and time periods, and by the lack of data on post-transplant maintenance, we confirmed the association of pre-HCT MRD with relapse risk. CD34+ selection has no impact on the risk of relapse. Relapse continues to be the major cause of death in AML/MDS patients following allogeneic hematopoietic cell transplantation (HCT). Advanced age has emerged as a strong predictor of relapse due to both generally increased disease risk and reduced ability to deliver myeloablative conditioning due to comorbidities and functional impairment. The impact of measurable residual disease (MRD) prior to HCT has not been assessed in the context of older patients receiving CD34+ selected allografts. We retrospectively examined 297 AML/MDS patients aged 60 years and older who underwent first allo-HCT at our institution from 2001 to 2016. We included only patients who received either a conventional or CD34+ selected graft. We collected MRD data using flow cytometry, cytogenetics (karyotype and/or FISH), and molecular mutation analysis from patients who had achieved a hematologic complete remission pre-HCT. Factors associated with the cumulative incidence of relapse (RI) and progression-free survival (PFS) were analyzed using cause-specific hazard models. The median age was 65.8 years (range 60-78.4), and 42% were women. One hundred and eighty-four patients had AML (62%). Fifty-nine percent of patients had HCT-CI >2; 51% had pre-HCT KPS >80; and 37% had high/very high disease risk index (DRI). Seventy-five percent of patients received a myeloablative regimen and 61% received a CD34+ selected graft. Sixteen percent of patients had a mismatched donor. With a median follow-up of 5.1 year for survivors, the 2- and 5-year overall survival was 50% (95% CI: 44-55) and 39% (95% CI: 33-45) respectively. The 2- and 5-year of PFS was 46% (95% CI: 40-51) and 37% (95% CI: 31-43) respectively. By June 30, 2018, 93 patients had relapsed, or their disease progressed, with 3-year cumulative RI of 31% (95% CI: 26-36). Two hundred and four patients had available MRD data and 71, 35%, were MRD positive pre-HCT. In multivariate analysis of RI (Table below), high/very high DRI score (HR 2.2, 95% CI: 1.3-3.8, p=0.004) and MRD positivity (HR 1.9, 95% CI: 1.1-3.2, p=0.027) were associated with an increased risk, with CD34+ selection approaching statistical significance for a reduced risk (HR 0.6, 95% CI: 0.3-1, p=0.064). In multivariate analysis of PFS, only high/very high DRI score (HR 1.8, 95% CI: 1.2-2.7, p=0.003) was associated with an increased risk. In this study, we characterized relapse following allogeneic HCT in an older cohort of AML/MDS patients. While limited by the retrospective nature with likely underestimation of MRD status due to different assays and time periods, and by the lack of data on post-transplant maintenance, we confirmed the association of pre-HCT MRD with relapse risk. CD34+ selection has no impact on the risk of relapse." @default.
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• W2912278056 title "Impact of Pre-Transplant Measurable Residual Disease on Relapse Incidence and Progression-Free Survival in Older AML/MDS Patients Following Allogeneic Hematopoietic Cell Transplantation" @default.
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