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Background: Significant racial differences have been observed in the incidence and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) in the United States, but to the authors' knowledge it remains unclear whether genomic differences contribute to these disparities., Methods: To understand the influences of genetic ancestry on tumor genomic alterations, the authors estimated the genetic ancestry of 1001 previously described patients with DLBCL using unsupervised model-based Admixture global ancestry analysis applied to exome sequencing data and examined the mutational profile of 150 DLBCL driver genes in tumors obtained from this cohort., Results: Global ancestry prediction identified 619 patients with >90% European ancestry, 81 patients with >90% African ancestry, and 50 patients with >90% Asian ancestry. Compared with patients with DLBCL with European ancestry, patients with African ancestry were aged >10 years younger at the time of diagnosis and were more likely to present with B symptoms, elevated serum lactate dehydrogenase, extranodal disease, and advanced stage disease. Patients with African ancestry demonstrated worse overall survival compared with patients with European ancestry (median, 4.9 years vs 8.8 years; P = .04). Recurrent mutations of MLL2 (KMT2D), HIST1H1E, MYD88, BCL2, and PIM1 were found across all ancestry groups, suggesting shared mechanisms underlying tumor biology. The authors also identified 6 DLBCL driver genes that were more commonly mutated in patients with African ancestry compared with patients with European ancestry: ATM (21.0% vs 7.75%; P < .001), MGA (19.7% vs 5.33%; P < .001), SETD2 (17.3% vs 5.17%; P < .001), TET2 (12.3% vs 5.82%; P = .029), MLL3 (KMT2C) (11.1% vs 4.36%; P = .013), and DNMT3A (11.1% vs 4.52%; P = .016)., Conclusions: Distinct prevalence and patterns of mutation highlight an important difference in the mutational landscapes of DLBCL arising in different ancestry groups. To the authors' knowledge, the results of the current study provide the first-ever characterization of genetic alterations among patients with African descent who are diagnosed with DLBCL., (© 2020 American Cancer Society.)

In an article published in this issue of Cancer, D'Arcy et al link the incidence of cancer among recipients of solid organ transplantation (SOT) in the Scientific Registry of Transplant Recipients with data from regional and statewide cancer registries to examine cancer-specific mortality for common malignancies in SOT recipients. This analysis helps to illuminate the role of immune surveillance across a broad range of malignancies and compares the incidence of cancers due to virally mediated oncogenesis (lymphoma, squamous cell carcinoma of the aerodigestive epithelium, and hepatitis-induced liver cancer) with the incidence of other malignancies. The authors' central finding is that cancer-specific mortality is significantly increased in SOT recipients in comparison with nontransplant recipients for multiple cancers, and the increased cancer incidence is not limited to the effects of viral oncogenesis. The authors document a significant increase in common epithelial malignancies that are currently treated with immune checkpoint antibodies, including melanoma, bladder cancer, colorectal cancer, cancers of the oral cavity/pharynx, kidney cancer, and lung cancer, and this supports the hypothesis that post-SOT immunosuppression affects immune surveillance in these cancers. Provocatively, the authors also document increases in the incidence and mortality of cancers not typically responsive to immune checkpoint therapies, including breast cancer and pancreatic cancer. The findings of D'Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration-approved antibodies to CTLA4 and PD-1/PD-L1., (© 2019 American Cancer Society.)

Background: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set., Methods: Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists. The patient characteristics, immunosuppressive regimen, treatment, survival, and follow-up time for 306 cases were extracted from 94 articles, and these cases were combined with 11 cases from Emory University Hospital. Patients with a recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox proportional hazards regression analyses identified predictors of overall survival (OS) for each subtype and B-cell subgroup., Results: OS differed significantly between monomorphic T-cell neoplasms (median, 9 months) and polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median OS was not reached (P = .0001). Significant differences in OS among B subgroups were not detected, but there was a trend toward decreased survival for patients with Burkitt-type PTLD. Kidney transplantation and a reduction of immunosuppression were associated with increased OS for patients with B-cell neoplasms in a multivariate analysis. Immunosuppression with azathioprine was associated with decreased OS for patients with T-cell neoplasms, whereas radiotherapy was associated with improved OS for patients with that subtype., Conclusions: The histologic subtype represents an important prognostic factor in PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower survival for certain subsets of patients with B-cell PTLD should be explored further and suggests the need for subtype-specific therapies to improve outcomes. Cancer 2018;124:2327-36. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background: Although the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients aged >80 years are less clear., Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to characterize presentation, treatment, and survival patterns in patients with DLBCL who were diagnosed between 2002 and 2009. Chi-square tests compared characteristics and initial treatments among patients with DLBCL who were aged >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients aged >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival., Results: Among 4635 patients with DLBCL, 1156 (25%) were aged >80 years. Patients aged >80 years were less likely to receive R-CHOP and more likely to be observed or receive the combination of rituximab, cyclophosphamide, vincristine, and prednisone (P<.0001 for both). Marital status, stage of disease, disease site, performance status, radiotherapy, and growth factor support were associated with initial R-CHOP in patients aged >80 years. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen found to be associated with improved overall survival (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62) and lymphoma-related survival (hazard ratio, 0.58; 95% confidence interval, 0.38-0.88)., Conclusions: Although patients with DLBCL who were aged >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of treatment of DLBCL on quality of life among patients in this age group., (© 2015 American Cancer Society.)