Delayed T cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults

• Selection of GVHD prophylaxis affects post-transplant immune reconstitution.

• In adults, early CD4 recovery is associated with improved OS, PFS and TRM, but not relapse, incidence of infections, or chronic GVHD.

Allogeneic hematopoietic cell transplantation (alloHCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T and B cell recovery have improved survival and decreased treatment-related mortality (TRM). 2089 patients were included who underwent first alloHCT for AML/ALL/MDS from 2008 to 2019 reported to CIBMTR with available CD4 counts at days 100 (D100) and 180 (D180). Patients (median age 51, range 2-75) were categorized into four groups based on GVHD prophylaxis: ex-vivo T cell depletion (TCD/CD34), post-transplant cyclophosphamide (PTCy), calcineurin-inhibitor alone (CNI) or with anti-thymocyte globulin (CNI+ATG). Based upon survival we could identify optimal cut-points for CD4+ T cells in pediatric (age <20y) patients: 248 x 106/L and 420 x 106/L at D100 and D180, respectively; and in adult (age >20y) patients: 104 x 106/L and 115 x 106/L at D100 and D180, respectively. In adults, D100 CD4 count was associated with overall survival, progression-free survival (PFS) and TRM, but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cut-point at D180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.