Konuma Takaaki, Kanda Junya, Uchida Naoyuki, Nishijima Akihiko, Tanaka Masatsugu, Ozawa Yukiyasu, Sawa Masashi, Onizuka Makoto, Ota Shuichi, Maruyama Yumiko, Kanda Yoshinobu, Kawakita Toshiro, Ara Takahide, Eto Tetsuya, Nakamae Hirohisa, Kimura Takafumi, Fukuda Takahiro, Atsuta Yoshiko
Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hematol Oncol. 2023 Feb;41(1):147-158. doi: 10.1002/hon.3094. Epub 2022 Oct 31.
The impact of conditioning intensity on different donor groups has been unclear in allogeneic transplantation. The objective of this study was to clarify the effect of conditioning intensity on disease-free survival (DFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host disease for each donor type. We retrospectively evaluated the effect of conditioning intensity on transplant outcomes for patients with acute leukemia or myelodysplastic syndrome aged between 16 and 60 years in Japan using the transplant conditioning intensity (TCI) scoring system. A total of 8526 patients who received first allogeneic transplantation from 6/6 antigen-matched sibling donor (MSD, n = 2768), 8/8 allele-matched unrelated donor (MUD, n = 2357), and unrelated single-cord blood (UCB, n = 3401) were eligible for the analyses. Compared to conditioning with TCI score 4.0, which was corresponds to conventional myeloablative conditioning, including cyclophosphamide with total body irradiation 12 Gy or busulfan 12.8 mg, and was considered as the reference group in the multivariate analyses, intensified conditioning with TCI score ≥4.5 improved DFS (hazard ratio [HR],0.81, P < 0.001) and relapse rate (HR, 0.70, P < 0.001) but only after UCB transplants and not MSD and MUD transplants. In contrast, NRM was higher after intensified conditioning with TCI score ≥4.5 for MSD (HR, 1.39, P = 0.008) and MUD (HR, 1.47, P = 0.002) transplants but not UCB transplants (HR, 1.12, P = 0.240). Neutrophil engraftment was also significantly higher after intensified conditioning with TCI score ≥4.5 but only for UCB transplants (HR, 1.24, P < 0.001), whereas it was significantly lower after reduced-intensity conditioning with TCI score ≤3.5 for MSD transplants only (HR, 0.82, P < 0.001). These data demonstrated that an intensified conditioning regimen improved survival and engraftment rate only after a UCB transplants. Therefore, TCI scoring system could enable the optimization of conditioning intensity according to donor type, particularly in terms of survival and engraftment.
在异基因移植中，预处理强度对不同供体组的影响尚不清楚。本研究的目的是明确预处理强度对每种供体类型的无病生存期（DFS）、复发、非复发死亡率（NRM）、中性粒细胞植入以及移植物抗宿主病的影响。我们使用移植预处理强度（TCI）评分系统，回顾性评估了预处理强度对日本16至60岁急性白血病或骨髓增生异常综合征患者移植结局的影响。共有8526例接受首次异基因移植的患者符合分析条件，这些患者分别来自6/6抗原匹配的同胞供体（MSD，n = 2768）、8/8等位基因匹配的无关供体（MUD，n = 2357）以及无关单份脐血（UCB，n = 3401）。与TCI评分为4.0的预处理相比（对应于传统的清髓性预处理，包括环磷酰胺联合12 Gy全身照射或白消安12.8 mg，在多变量分析中被视为参考组），TCI评分≥4.5的强化预处理改善了DFS（风险比[HR]，0.81，P < 0.001）和复发率（HR，0.70，P < 0.001），但仅在脐血移植后出现，而在同胞供体和无关供体移植后未出现。相反，对于MSD（HR，1.39，P = 0.008）和MUD（HR，1.47，P = 0.002）移植，TCI评分≥4.5的强化预处理后NRM较高，而脐血移植后则不然（HR，1.12，P = 0.240）。TCI评分≥4.5的强化预处理后中性粒细胞植入也显著更高，但仅在脐血移植后出现（HR，1.24，P < 0.001），而仅对于MSD移植，TCI评分≤3.5的减低强度预处理后中性粒细胞植入显著更低（HR，0.82，P < 0.001）。这些数据表明，强化预处理方案仅在脐血移植后改善了生存率和植入率。因此，TCI评分系统能够根据供体类型优化预处理强度，特别是在生存率和植入方面。
