Impact of infused CD34+ stem cell dosing for allogeneic peripheral blood stem cell transplantation with post-transplant cyclophosphamide

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 7; pp. 1683 - 1690
• Main Authors: Elmariah, Hany, Naqvi, Syeda Mahrukh Hussnain, Kim, Jongphil, Nishihori, Taiga, Mishra, Asmita, Perez, Lia, Faramand, Rawan, Lazaryan, Aleksandr, Liu, Hien D, Khimani, Farhad, Nieder, Michael, Anasetti, Claudio, Pidala, Joseph, Bejanyan, Nelli
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2021
• Subjects: Blood; Bone marrow; Bone marrow transplantation; Care and treatment; CD3 antigen; CD34 antigen; Cyclophosphamide; Dosage; Dosage and administration; Graft-versus-host reaction; Health aspects; Hematopoietic stem cells; Leukemia; Lymphocytes T; Lymphomas; Malignancy; Multivariate analysis; Patient outcomes; Patients; Peripheral blood; Prophylaxis; Stem cell transplantation; Stem cells; Survival; T cells; Transplantation; Transplants & implants; United States
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-021-01219-8

Higher infused total nucleated cell dose (TNC) in allogeneic bone marrow transplant (BMT) with post-transplant cyclophosphamide (PTCy) is associated with improved overall survival. As many centers prefer peripheral blood stem cell grafts (PBSCT) with PTCy, the effect of cell dose on outcomes with this platform also requires elucidation. We retrospectively evaluated 144 consecutive adult patients who received allogeneic T-cell replete PBSCT with PTCy-based graft-versus-host disease (GVHD) prophylaxis for a hematologic malignancy from 2012-2018. The infused CD34+ cell dose was stratified into low (<5 × 10 /kg), intermediate (5-10 × 10 /kg) and high (>10 × 10 /kg) dose level groups. In multivariate analysis, the low CD34+ cell dose group had worse non-relapse mortality (HR = 4.51, 95% CI: 1.92-10.58, p < 0.001), progression- free survival (HR = 4.11, 95% CI: 2.07-8.15, p < 0.001), and overall survival (HR = 4.06, 95% CI: 2.00-8.25, p ≤ 0.001) compared to the intermediate group. Clinical outcomes between the intermediate and high CD34+ cell dose groups were similar. TNC and CD3+ cell dose had no significant impacts on outcomes. These findings suggest that, in patients receiving allogeneic PBSCT with PTCy, infused CD34+ cell doses >5 × 10  cells/kg may result in improved survival. Thus, this study supports targeting a CD34+ cell dose of >5 × 10 cells/kg for allogeneic PBSCT with PTCy.