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

Alexandre G Troullioud Lucas, Caroline A Lindemans, Senthil Velan Bhoopalan, Rana Dandis, Susan E Prockop, Swati Naik, Dinesh Keerthi, Coco de Koning, Akshay Sharma, Stefan Nierkens, Jaap Jan Boelens

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)977-985
Number of pages9
Issue number9
Publication statusPublished - Sept 2023


  • Child
  • Young Adult
  • Humans
  • Hematopoietic Stem Cell Transplantation/methods
  • Retrospective Studies
  • Immune Reconstitution
  • Transplantation, Homologous
  • Graft vs Host Disease/etiology
  • Hematologic Neoplasms/therapy
  • Leukemia, Myeloid, Acute


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