Impact of CD34+ Graft Cell Dose on Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation

Background:

CD34+ graft cell dose is imperative to outcomes after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). A few studies have evaluated the effect of graft cell dose on outcomes after allo-PBSCT; however, the data is limited and heterogeneous. We aimed to investigate the impact of graft cell dose on outcomes following allo-PBSCT.

Methods:

In this retrospective single-center study, we included all patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-PBSCT (n=224) at the University of Kanas Medical Center from August 2016 to July 2021. Cox regression analysis compared overall survival (OS) and disease-free survival (DFS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Logistic regression was performed to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Odds ratios (0R) with 95% 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. SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p<0.05.

Results:

We included 224 allo-PBSCT recipients who received a MUD (n=110) or Haplo (n=114) PBSCT. The median recipient age was 56.75 (19.23-74.40) years, and 63% (n=141) of patients were male. The median graft cell dose was 5.63 (0.98-16.6) million CD34+ cells per kg. The median graft cell dose in MUD PBSCT recipients was 7.22 million CD34+ cells/kg, and the median graft cell dose in haplo PBSCT recipients was 5.03 million CD34+ cells/kg. Graft cell dose was categorized as <5 (29%, n=64), 5-8 (48%, n=108), and >8 million (23%, n=52) CD34+ cells/kg. Myeloablative and reduced-intensity conditioning were performed in 88 (39%) and 136 (61%) recipients. GVHD prophylaxis included tacrolimus/methotrexate (n=98, 44%) and post-transplant cyclophosphamide-based (n=126, 56%). Hematologic diagnoses included myeloid (n=157, 70%), lymphoid (n=54, 24%), and others (n=13, 6%). After adjusting for significant variables in the multivariate regression models, a higher graft cell dose was significantly associated with faster neutrophil engraftment (R=-0.256, 95% CI -0.448 to -0.064, p=0.0091) and faster platelet engraftment (R=-1.054, 95% CI -1.945 to -0.163, p=0.02). There was no significant association of graft cell dose with OS, DFS, Relapse, NRM, acute and chronic GVHD, and GRFS. Similar trends were seen in sub-group analysis by donor type (MUD and haplo). A higher graft cell dose (>8 million CD34 cells per kg) did not adversely impact post-transplant outcomes. A lower graft cell dose (<5 million CD34 cells per kg) was associated with slower engraftment.

Conclusion:

Higher CD34+ graft cell dose results in faster neutrophil and platelet engraftment after allogeneic peripheral blood stem cell transplantation; however, graft cell dose does not significantly impact other post-transplant outcomes. The optimal graft cell dose after allo-PBSCT might be over 5 million CD34+ cells/kg. Our findings should be validated in a larger cohort of patients.

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