Related Experiment Video
Updated: Jul 26, 2025
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Early immune reconstitution as predictor for outcomes after allogeneic hematopoietic cell transplant; a
Alexandre G Troullioud Lucas1, Caroline A Lindemans2, Senthil Velan Bhoopalan3
1Transplantation and Cellular Therapy, MSK Kids, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Insights
Early CD4 and B-cell immune reconstitution after allogeneic stem cell transplant significantly lowers non-relapse mortality and GVHD. In acute myeloid leukemia patients, this reconstitution also reduces relapse risk, highlighting its importance for outcomes.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Allogeneic hematopoietic cell transplant (allo-HCT) is a critical treatment for hematological malignancies.
- CD4 immune reconstitution (IR) post-transplant is linked to better outcomes, but its specific impact on leukemia relapse, particularly in pediatric patients, requires further investigation.
Purpose of the Study:
- To investigate the correlation between the immune reconstitution of lymphocyte subsets and transplant outcomes in pediatric and young adult patients with hematological malignancies.
- To determine the impact of CD4, CD8, B-cell, and NK-cell reconstitution on non-relapse mortality (NRM), graft-versus-host disease (GVHD), and relapse risk.
Main Methods:
- Retrospective analysis of 503 patients undergoing first allo-HCT for hematological malignancies between 2008-2019.
- Utilized Cox proportional hazard and Fine-Gray competing risk models to assess the impact of immune reconstitution on transplant outcomes.
- Analyzed CD4, CD8, B-cell, and NK-cell levels at specific time points post-transplant.
Main Results:
- Early CD4 and/or B-cell immune reconstitution (e.g., CD4 >50 cells/μL, B cells >25 cells/μL by day 100) significantly predicted lower NRM (HR 0.26 for CD4 IR; HR 0.06 for CD4 and B cell IR).
- CD4 and B-cell IR was also associated with reduced risks of acute GVHD (HR 0.02) and chronic GVHD (HR 0.16).
- In the acute myeloid leukemia subgroup, CD4 and B-cell IR correlated with a lower risk of disease relapse (HR 0.24). No significant correlation was found for CD8 and NK-cell IR with relapse or NRM.
Conclusions:
- CD4 and B-cell immune reconstitution post-allo-HCT is a significant predictor of reduced NRM and GVHD across the cohort.
- In pediatric patients with acute myeloid leukemia, CD4 and B-cell IR is associated with a decreased risk of relapse.
- These findings suggest that monitoring CD4 and B-cell reconstitution can aid in risk stratification and clinical decision-making following allo-HCT.
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.
