Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation.

Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.

Black patients with multiple myeloma have better survival than white patients when treated equally: a matched cohort study.

We assessed differences in survival between non-Hispanic black (NHB) and non-Hispanic white (NHW) patients with multiple myeloma (MM), and the sequential effects of patient characteristics, and diagnosis and treatment-related factors on the survival disparity using data from 3319 NHB and 20,831 NHW MM patients in the SEER-Medicare (1999-2017) database. Four sets of 3319 NHWs were matched sequentially to the same set of 3319 NHBs, based on demographics (age, sex, year of diagnosis, marital status, and SEER site), socioeconomic status (SES, demographics plus SES), presentation factors (SES variables plus comorbidity), and treatment factors (presentation variables plus antimyeloma therapies). We found NHBs were less likely to receive treatment than NHWs even among patients matched for demographics, SES, and comorbidities. The absolute difference in 5-year survival between NHBs and NHWs was not significant in the demographics match (0.6%; P = 0.30) and remained non-significant after matching for SES (1.4%, P = 0.17). When matching for presentation, NHBs had significantly longer 5-year survival than NHWs (absolute difference = 3.8%, P = 0.003). Additional matching on treatment-related factors further enlarged the racial difference in 5-year survival to 4.6% (P < 0.001). Our findings reinforce the importance of equitable access to effective treatment modalities to further improve the survival of NHB patients with MM.