Preconditioning Absolute Lymphocyte Count and Transplantation Outcomes in Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Reduced-Intensity Conditioning and Antithymocyte Globulin Treatment

Abstract

The integration of antithymocyte globulin (ATG) into therapy has significantly reduced the incidence of graft-versus-host disease (GVHD) and is being actively used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The ATG dosage is determined by the recipient's body weight, but some insist that this approach does not reflect the actual target of ATG. In this respect, weight-based dosing may lead to ATG overdose, particularly in recipients with a relatively low absolute lymphocyte count (ALC). We retrospectively analyzed 84 patients with acute leukemia or myelodysplastic syndrome who underwent matched related donor (MRD) allo-HSCT with reduced-intensity conditioning (RIC) at a single institution. Patients were dichotomized according to the ALC measured on the first day of conditioning (day -7) to investigate the associations of the ALC with GVHD and survival outcomes. The median duration of follow-up was 29 months. The preconditioning ALC was closely correlated with the ALC at the first ATG administration (day -3). The cumulative incidences of both acute GVHD and chronic GVHD were significantly lower in the preconditioning ALC <500/μL group compared with the ALC ≥500/μL group. There was no significant difference in disease relapse incidence between the 2 groups; however, mortality was significantly higher in the ALC <500/μL group. Multivariate analysis including disease status, modified European Blood and Marrow Transplantation score, and preconditioning ALC (≥500/μL versus <500/μL) identified disease status and ALC as being independently associated with overall survival (OS). In particular, infection was the most common cause of death in the ALC <500/μL group. Our data suggest that uniform weight-based ATG dosing in MRD allo-HSCT with RIC is associated with an increase in nonrelapse mortality and a relatively inferior OS in patients with a significantly low preconditioning ALC. Therefore, alternative strategies for the integration of ATG should be considered in allo-HSCT, at least for patients with a substantially low preconditioning ALC.