Effect of CD34+ Cell Dose on the Outcomes of Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide

Abstract

The impact of infused CD34⁺ cell dose on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplantation cyclophosphamide (PTCy). We aimed to assess the effect of CD34⁺ cell dose in peripheral blood stem cell (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis. To do so, we conducted a single-center retrospective analysis of 221 consecutive adult patients who underwent PTCy alloHSCT from HLA-matched sibling donors (MSDs; n = 22), HLA-matched unrelated donors (MUDs; n = 83), mismatched unrelated donors (MMUDs; n = 73), and haploidentical donors (n = 43). Based on the binary partitioning method, 5 × 10⁶/kg was used as the optimal cutoff for CD34⁺ cell dose. According to our institutional protocol, the maximum CD34⁺ cell dose was capped at 8 × 10⁶/kg. The study cohort was divided into 2 groups based on CD34⁺ cell dose: high dose (>5 to 8 × 10⁶/kg) and low dose (≤5 × 10⁶/kg). Patients receiving high-dose CD34⁺-containing grafts had significantly shorter median times to neutrophil engraftment and platelet engraftment compared to those who received low-dose CD34+ (19 days versus 21 days [P = .002] and 16 days versus 22 days [P = .04], respectively). There were no differences between the high-dose and low-dose groups in the cumulative incidence of day +100 acute GVHD (grade II-IV: 25% versus 23% [P = .7]; grade III-IV: 5% versus 4% [P = .4], respectively) or 2-year chronic GVHD (moderate/severe GVHD: 9% versus 6%; P = .5). There was no impact of CD34⁺ cell dose on survival outcomes with the use of MSDs, MUDs, or MMUDs. Recipients of haploidentical alloHSCT using low-dose CD34⁺ cells had significantly worse overall survival (hazard ratio [HR], 6.01; P = .004) and relapse-free survival (HR, 4.57; P = .004). In recipients of PBSC PTCy alloHSCT, infused CD34⁺ cell doses >5 to 8 × 10⁶/kg were associated with faster neutrophil and platelet engraftment, independent of donor type. Our study suggests an impact of CD34⁺ cell dose on survival outcomes only with haploidentical donors, for whom the administration of a CD34⁺ cell dose ≤5 × 10⁶/kg significantly decreased survival outcomes.

Keywords: Allogeneic hematopoietic stem cell transplantation; CD34(+) cell dose; Graft; Haploidentical donor; Post-transplantation cyclophosphamide.