Early immune reconstitution as predictor for outcomes after allogeneic hematopoietic cell transplant; a tri-institutional analysis.

Background Aims: CD4 immune reconstitution (IR) after allogeneic hematopoietic cell transplant (allo-HCT) correlates with lower non-relapse mortality (NRM), but its impact on leukemia relapse remains less clear, especially in children. We studied the correlation between IR of lymphocyte subsets and HCT outcomes in a large cohort of children/young adults with hematological malignancies.
Methods: We retrospectively analyzed CD4, CD8, B-cell and natural killer (NK) cell reconstitution in patients after first allo-HCT for a hematological malignancy at three large academic institutions (n = 503; period 2008-2019). We used Cox proportional hazard and Fine-Gray competing risk models, martingale residual plots and maximally selected log-rank statistics to assess the impact of IR on outcomes.
Results: Achieving CD4 >50 and/or B cells >25 cells/μL before day 100 after allo-HCT was a predictor of lower NRM (CD4 IR: hazard ratio [HR] 0.26, 95% confidence interval [CI] 0.11-0.62, P = 0.002; CD4 and B cell IR: HR 0.06, 95% CI 0.03-0.16, P < 0.001), acute graft-versus-host disease (GVHD) (CD4 and B cell IR: HR 0.02, 95% CI 0.01-0.04, P < 0.001) and chronic GVHD (CD4 and B cell IR: HR 0.16, 95% CI 0.05-0.49, P = 0.001) in the full cohort, and of lower risk of relapse (CD4 and B cell IR: HR 0.24, 95% CI 0.06-0.92, P = 0.038) in the acute myeloid leukemia subgroup. No correlation between CD8 and NK-cell IR and relapse or NRM was found.
Conclusions: CD4 and B-cell IR was associated with clinically significant lower NRM, GVHD and, in patients with acute myeloid leukemia, disease relapse. CD8 and NK-cell IR was neither associated with relapse nor NRM. If confirmed in other cohorts, these results can be easily implemented for risk stratification and clinical decision making.
Competing Interests: Conflicts of Interest CL reports honoraria for a lecture from Genzyme and is on a Data Safety Monitoring Board of ExCellThera (related to this topic). SP reports support for the conduct of clinical trials: Jasper, Atara, AlloVir, Consulting/Advisory Board Participation CellEvolve, Smart Immune, Regeneron and IP related to VSTs licensed to Atara with all rights assigned to Memorial Sloan Kettering Cancer Center. AS has received consultant fee from Spotlight Therapeutics, Medexus Inc. and Vertex Pharmaceuticals. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. AS is the St. Jude Children's Research Hospital site principal investigator of clinical trials for genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics, Novartis Pharmaceuticals and Beam Therapeutics. The industry sponsors provide funding for the clinical trial, which includes salary support paid to his institution. AS has no direct financial interest in these therapies. None of these conflicts are related to the work presented here. JJB reports honoraria from Avrobio, BlueRock, Bluebird Bio, Sanofi, Sobi, SmartImmune, Advanced Clinical consulting (not related to this topic). All other authors report no conflicts of interest.
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