Comparing transplant vs. non-transplant for de novo MDS by IPSS score
A study of 514 patients between 60-70 years old with de novo myelodysplastic syndromes (MDS) has shown that for patients with intermediate-2/high International Prognostic Scoring System (IPSS) scores, a reduced-intensity allogeneic transplant leads to a significantly longer life expectancy (LE) compared to non-transplantation therapies: 36 months vs. 28 months, respectively (p<0.001). Non-transplant treatments were best supportive care, hematopoietic growth factors, and hypomethylating agents. For patients with low/intermediate-1 IPSS scores, non-transplantation approaches led to significantly longer LE compared to reduced-intensity transplant: 77 months vs. 38 months, respectively (p<0.001).
Related, well-matched unrelated HCT outcomes comparable in MDS
Well-matched unrelated donor hematopoietic cell transplantation (HCT) yields comparable outcomes compared to matched related donor HCT in patients with MDS, according to a study of 701 adult MDS patients transplanted between 2002 and 2006 and reported to CIBMTR (Center for International Blood and Marrow Transplant Research). Median patient age was 53 years (range, 22-78), and 31% had Karnofsky performance scores <90% at time of transplant. Three-year survival for matched related transplants and 8/8 HLA-matched unrelated donor transplants were 44% and 39%, respectively (p=0.27). Three-year survival using 7/8 matched unrelated donors was 29%, significantly lower than matched related donors (p=0.01).
Similar survival using sibling, unrelated donor, and cord blood grafts in AML
Reduced-intensity conditioning HCT in patients 50 years and older with acute myelogenous leukemia (AML) in complete remission has similar outcomes using sibling donors, unrelated donors, and cord blood units, with adjusted three-year survival of 55%, 45%, and 43%, respectively (p=0.26). Three-year cumulative incidences of transplant-related mortality (TRM) were 18%, 14%, and 24%, respectively (p=0.22). In multivariate analysis, only poor-risk cytogenetics was associated with relapse (hazard ratio [HR], 1.7 [95% confidence interval, 1.0 to 3.0], p=0.04) and worse leukemia-free survival (HR, 1.6 [95% confidence interval, 1.0 to 2.5], p=0.03), but donor choice had no significant impact on survival (p=0.73).
Negative impact of minimal residual disease is similar for AML in CR1 and CR2
A single-center study of 253 consecutive patients with AML has shown that the negative impact of pre-transplant minimal residual disease (MRD) is similar for patients in first and second complete remission (CR1, CR2), and that even minute levels (≤0.1%) are associated with significantly worse outcomes. MRD was assessed in patients in CR1 (n=183) or CR2 (n=70) using pre-transplant marrow aspirates analyzed by 10-color flow cytometry. Three-year estimates of overall survival were 73% and 32% for MRD-negative and MRD-positive CR1 patients, respectively, and 73% and 44% for MRD-negative and MRD-positive CR2 patients. In a multivariate analysis of the entire patient cohort, adjusted risk of death was 2.61-times higher for MRD-positive patients (P<0.001).
Select older patients can undergo HCT, according to results of a study of 54 consecutive patients >70 years undergoing reduced-intensity transplantation between 2007 and 2012 at Massachusetts General Hospital (n=14) or the Dana-Farber Cancer Institute (n=40). Median age at transplantation was 71 years (range, 70 to 76), and the median HCT comorbidity index score was 1 (range, 0 to 5). Day-100 non-relapse mortality (NRM) was 3.7% and two-year NRM was 5.6%. Two-year cumulative incidence of chronic GVHD was 36%, and progression-free and overall survival were both 39%.
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