Department of Bone Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Bone Marrow Transplant. 2021 Jul;56(7):1683-1690. doi: 10.1038/s41409-021-01219-8. Epub 2021 Mar 3.
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.
在异基因骨髓移植(BMT)中,输注更高的总核细胞剂量(TNC)联合移植后环磷酰胺(PTCy)与总生存改善相关。由于许多中心更喜欢使用 PTCy 的外周血干细胞移植物(PBSCT),因此这种平台上的细胞剂量对结果的影响也需要阐明。我们回顾性评估了 2012 年至 2018 年期间,144 例连续接受异基因 T 细胞完全填充 PBSCT 联合 PTCy 作为移植物抗宿主病(GVHD)预防的血液系统恶性肿瘤成人患者。输注的 CD34+细胞剂量分为低(<5×10/kg)、中(5-10×10/kg)和高(>10×10/kg)剂量水平组。多变量分析显示,低 CD34+细胞剂量组无复发死亡率(HR=4.51,95%CI:1.92-10.58,p<0.001)、无进展生存(HR=4.11,95%CI:2.07-8.15,p<0.001)和总生存(HR=4.06,95%CI:2.00-8.25,p≤0.001)均差于中剂量组。中间组和高 CD34+细胞剂量组之间的临床结局相似。TNC 和 CD3+细胞剂量对结局没有显著影响。这些发现表明,在接受 PTCy 异基因 PBSCT 的患者中,输注 CD34+细胞剂量>5×10 细胞/kg 可能会改善生存。因此,本研究支持针对 PTCy 异基因 PBSCT 靶向 CD34+细胞剂量>5×10 细胞/kg。