Outcomes after Bone Marrow Versus Peripheral Blood Matched Unrelated Donor Hematopoietic Stem Cell Transplantation for Acute Leukemia

Background: Allogeneic hematopoietic stem cell transplantation (HCT) is a potential therapy for acute leukemia. Graft source might impact outcomes in patients undergoing matched unrelated donor (MUD) HCT. Our study compared the outcomes after bone marrow (BM) grafts versus peripheral blood stem cell (PBSC) grafts in patients with acute leukemia undergoing MUD HCT.

Methods: We conducteda retrospective multicenter analysis, including patients with acute leukemia receiving MUD HCT in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2008 to 2018 using the P5702 dataset by Guru Murthy et al. We examined the impact of graft source on post-transplant outcomes, including overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft versus host disease (GVHD), chronic GVHD, GVHD-free relapse-free survival (GRFS), and engraftment. 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 performed. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariate analysis and the clinically relevant variables were included in the multivariate models for OS, DFS, GRFS, relapse, NRM, and GVHD. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05.

Results: We analyzed 2924 MUD HCT recipients with acute leukemia, including acute myeloid leukemia (AML, 80%, n=2352) and acute lymphocytic leukemia (ALL, 20%, n=572). The graft types were BM in 571 (19.5%) and PB in 2353 (80.5%) recipients. The median age was 53 (years), and 54% of patients were male. Ethnicities were Caucasian (91%), African American (4%), and Asian and others (6%). Karnofsky's performance status was ≥90% in 58% of patients. The HCT-comorbidity Index was ≥3 in 46% of patients. Myeloablative conditioning was used in 68% of patients. GVHD prophylaxis regimens included tacrolimus-based (85%), cyclosporine-based (9%), post-transplant cyclophosphamide-based (5%), and others (1%). Anti-thymocyte globulin or alemtuzumab was used in 31.5% of patients. Cytomegalovirus serostatus was positive in 64% of recipients. The median follow-up time was 5.1 (5.03-5.33) years. Use of PBSC graft was associated with a lower incidence of primary graft failure (3% PBSC vs. 6% BM) and faster neutrophil (median months: 0.4 PBSC vs. 0.6 BM, p<0.001) and platelet engraftment (median months: 0.6 PBSC vs. 0.8 BM, p<0.001). However, an inferior GRFS (median years: 0.21 PBSC vs. 0.24 BM, p=0.022), higher NRM (22% PBSC vs. 17.5% BM, p=0.031), and higher chronic GVHD (50% PBSC vs. 37% BM, p<0.001). No significant differences between PBSC and BM graft types regarding OS (median years: 3.13 PBSC vs.4.11 BM, p=0.070), DFS (median years: 1.65 PBSC vs.1.95 BM, p=0.129), relapse (41% PBSC vs 40% BM, p=0.667), and acute GVHD (grade II-IV: 44% PBSC vs 41% BM, p=0.110; grade III-IV: 16% PBSC vs 15% BM, p=0.586). In the adjusted multivariate models, compared to BM grafts, PBSC compared to BM grafts demonstrated significantly inferior GRFS (HR 1.15, 95% CI 1.03-1.28), p=0.016) and increased incidence of chronic GVHD (HR 1.49, 95% CI 1.27-1.76, p<0.001).

Conclusion: In acute leukemia patients undergoing matched unrelated donor hematopoietic cell transplantation, we found that peripheral blood stem cells, compared to bone marrow grafts, were associated with faster neutrophil and platelet engraftment, a lower primary graft failure rate, inferior GVHD-free relapse-free survival, and higher chronic GVHD. There were no significant differences in overall survival, disease-free survival, relapse, acute GVHD, and non-relapse mortality incidence between patients receiving bone marrow and peripheral blood grafts.

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