Impaired CD4+ T-Cell Recovery after Autologous Stem Cell Transplantation in Patients with Myeloma and Lymphoma in the Modern Era

2020 
High dose chemotherapy followed by autologous stem cell transplantation (ASCT) offers a cure in the relapsed setting in both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Additionally, it remains a first-line standard of care in multiple myeloma (MM) patients whom are eligible for ASCT. However, the management of these hematologic malignancies continues to rapidly evolve with non-cytotoxic therapeutic options such as development of new cellular therapies. These developments underscore the importance of monitoring immune reconstitution after ASCT. Immune reconstitution panels (IRP) were evaluated retrospectively in all lymphoma and MM patients over a 6-year span (2012-2018) whom underwent ASCT at our institution. Patients were included if they had at least two IRP evaluations including (1) a pre-ASCT measured within 30 days of ASCT, (2) day 30-45, (3) day 60-90, and (4) at 1-year post-ASCT. Mononuclear cells from peripheral blood of treated patients were analyzed by flow cytometry for assessment of lymphocyte phenotype and numbers. The data on 110 patients were available for analysis (72 MM, 34 NHL, 4 HL). All lymphoma patients were conditioned with BEAM. All MM patients were conditioned with a standard high dose melphalan regimen. The median pre-ASCT absolute CD3 counts in the lymphoma cohort were significantly lower than the MM cohort at 1709 cells/μL vs 3309 cells/μL, respectively (P Impaired T-cell reconstitution in both lymphoma and MM continues through 1-year post-ASCT. As shown, a larger percent reduction in median CD3 and CD4 counts through day 365 was appreciated in MM compared to lymphoma. Impaired recovery of CD4+ T cells may increase the risk of opportunistic infections, decrease the response to vaccination, and lead to ineffective anti-tumor response. Further prospective and larger retrospective studies like this should continue in the modern-era as they may help predict responses to further interventions requiring a robust T-cell repertoire for maximal efficacy such as CAR-T cell and BiTE therapies.
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