Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Bone Marrow Transplantation

Background:

Outcomes following allogeneic bone marrow transplantation (allo-BMT) have been associated with several factors including the CD34+ graft cell dose. A few studies have evaluated the effect of graft cell dose on outcomes after allo-BMT; however, the literature is scarce and heterogeneous. We aimed to investigate the impact of graft cell dose on outcomes following allo-BMT.

Methods:

In this retrospective single-center study, we included all patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-BMT (n=228) at the University of Kanas Medical Center from August 2016 to July 2021. We used Cox regression analysis to compare overall survival (OS) and disease-free survival (DFS), and logistic regression to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Linear regression was performed to compare platelet and neutrophil engraftment, and the correlation coefficient (R) was calculated. Univariate and multivariate analyses were performed to explore the impact of graft cell dose. We used SPSS version 28 and R version 4.16 for data analysis and considered statistical significance at p<0.05.

Results:

We included 228 allo-BMT recipients who received a MUD (n=166) or Haplo (n=62) BMT. The median recipient age was 58 (18-77) years and 60% (n=136) were male. The median graft cell dose was 2.51 million CD34+ cells per kg. Graft cell dose was categorized as <2 (35%, n=79), 2-3 (29%, n=67), and >3 million (36%, n=82) CD34+ cells/kg. Myeloablative and reduced-intensity conditioning were performed in 81 (36%) and 147 (64%) recipients. GVHD prophylaxis included tacrolimus/methotrexate (n=143, 63%) and post-transplant cyclophosphamide-based (n=85, 37%). Hematologic diagnoses included myeloid (n=165, 72%), lymphoid (n=47, 21%), and others (n=16, 7%). After adjusting for significant variables in the multivariate regression models, a higher graft cell dose was significantly associated with faster platelet engraftment (R -2.74, 95% CI -4.752 to -0.745, p=0.0074) and superior one-year GRFS (OR 1.27, 95% CI 1.02-1.61, p= 0.037). Graft cell dose <2 million/kg CD34+ cells was associated with slower platelet engraftment (R 6.947, 95% CI 1.032-12.861, p=0.0215) and inferior one-year GRFS (OR 0.47, 95% CI CI 0.24- 0.92, p=0.03). There was no significant association of graft cell dose with OS, DFS, Relapse, NRM, acute and chronic GVHD, and neutrophil engraftment. We also stratified the analysis by donor type. Among MUD BMT recipients, similar results were seen with faster platelet engraftment with higher graft cell dose (R -2.791, 95% CI -4.968 to -0.615, p=0.0123) and there was no impact on other post-transplant outcomes while graft cell dose was not significantly associated with any post-transplant outcomes investigated among the haplo BMT recipients.

Conclusion:

Higher CD34+ graft cell dose results in faster platelet engraftment and superior GVHD-free Relapse-free survival after allogeneic bone marrow transplantation; however, graft cell dose does not significantly impact other post-transplant outcomes. The optimal graft cell dose after allo-BMT might be over 2 million CD34+ cells/kg. Our findings should be validated in a larger cohort of patients.

Ahmed:Bristol Myers Squibb: Consultancy; Kite, a Gilead Company: Research Funding. Abhyankar:Incyte: Consultancy; CSL Behring, Miltenyi Biotec.: Research Funding. McGuirk:NEKTAR therapeutics: Consultancy; Envision: Consultancy; Autolus: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy; Legend biotech: Consultancy; Sana technologies: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.