Impact of Graft Cell Dose on Outcomes after Matched Sibling Donor Bone Marrow Transplantation with Post-Transplant Cyclophosphamide-Based GvHD Prophylaxis

Background: CD34+ graft cell dose might affect outcomes after matched sibling donor (MSD) bone marrow transplantation (BMT) with post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis. We aimed to investigate the impact of graft cell dose on the outcomes after MSD BMT with PT-Cy-based GVHD prophylaxis.

Methods: A retrospective multicenter analysis was conducted, including MSD BMT recipients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. We examined the impact of conditioning intensity on post-transplant outcomes, including overall survival (OS), disease-free survival (DFS), relapse, grade 2-4 acute GVHD (aGVHD), chronic GVHD (cGvHD), and GvHD-free relapse-free survival (GRFS). Patient-, disease- and transplant-related factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox proportional hazards regression analyses were used for OS, DFS, GRFS, aGVHD, cGVHD, and relapse outcomes. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. A significance level of 0.05 was used throughout. Statistical analyses were conducted using Stata version 18.

Results: We included 71 MSD BMT recipients with PT-Cy-based GVHD prophylaxis. The median age was 46.6 (29-60.5) years, and 62% (n=44) were male. Ethnicities were Caucasian (72%, n=51), African American (15%, n=11) and Hispanic (13%, n=9). Forty-five patients (63%) had a Karnofsky performance score of 90% or higher, and 44% (n=31) had a comorbidity index of 3 or higher. Hematologic diagnoses included acute myeloid leukemia (45%, n=32), acute lymphoblastic leukemia (25%, n=18), and myelodysplastic syndromes (25%, n=18). Myeloablative and reduced-intensity conditioning were performed in 45% (n=32) and 55% (n=39) recipients respectively. Growth factor was used in 72% (n=51) of patients. The graft cell dose was 0-2 million CD34 cells/kg (39%, n=28) and over 2 million CD34 cells/kg (61%, n=43). The median follow-up time was 3.71 (95% CI 3-4.99) years. The median OS was not reached. The median DFS and GRFS were 0.71 years (95% CI 0.50-2.04) and 0.32 years (95% CI 0.19-0.47) respectively. After adjusting for significant variables in the multivariate regression models, use of higher graft cell dose (over 2 million CD34+ cells/kg) did not show any significant differences in OS (HR 1.15, 95% CI 0.44-3.00, p=0.780), DFS (HR 1.87, 95% CI 0.78-4.46, p=0.158), GRFS (HR 1.69, 95% CI 0.87-3.26, p=0.119), relapse (HR 1.69, 95% CI 0.56-5.08, p=0.348), aGVHD (HR 1.85, 95% CI 0.69-4.93, p=0.221) and cGVHD (HR 2.67, 95% CI 0.62-11.55, p=0.188).

Conclusion: Our study did not find a significant association between graft cell dose and matched sibling donor-bone marrow transplantation outcomes with post-transplant cyclophosphamide-based GVHD prophylaxis.

Abhyankar:CSL Behring, Miltenyi Biotec.: Research Funding; Incyte: Consultancy. Hamadani:Sanofi Genzyme: Speakers Bureau; Autolus: Consultancy; Forte Biosciences: Consultancy; AbbVie: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; BMS: Consultancy; Genentech: Speakers Bureau; Astellas Pharma: Research Funding; Omeros: Consultancy; CRISPR: Consultancy; Allovir: Consultancy; Caribou: Consultancy; Spectrum Pharmaceuticals: Research Funding; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Takeda: Research Funding. McGuirk:BMS: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Legend biotech: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Kite: Consultancy; Novartis: Consultancy; Autolus: Consultancy; Caribou bio: Consultancy; Sana technologies: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.