BMT Unit, Humanitas Clinical and Research Center-IRCCS, Humanitas Cancer Center, Milan, Italy.
Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center-IRCCS, Humanitas Cancer Center, Milan, Italy.
Transplant Cell Ther. 2021 Jun;27(6):492.e1-492.e6. doi: 10.1016/j.jtct.2021.03.013. Epub 2021 Mar 15.
Low-dose total body irradiation (TBI) has long been used in nonmyeloablative conditioning (NMAC) regimens before allogeneic stem cell transplantation from haploidentical donors (haplo-SCT). More recently, the use of total marrow lymphoid irradiation (TMLI) instead of TBI in conditioning is increasing. This study aimed to evaluate outcomes in a cohort of patients treated with low-dose TMLI in terms of engraftment, full donor chimerism status, graft-versus-host disease (GVHD), and extrahematologic toxicities, and to compare these outcomes with those in a cohort of patients receiving conventional TBI-containing conditioning. This retrospective single-center study included 100 patients with advanced hematologic malignancies who underwent haplo-SCT. Between 2009 and 2011, the NMAC regimen consisted of cyclophosphamide, fludarabine, and low-dose TBI (2 Gy), and after 2011, TBI was replaced with TMLI (2 Gy). Patients received post-transplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil as GVHD prophylaxis. For all patients, the median time to absolute neutrophil count (ANC) recovery to >0.5 × 10/L was 21 days (range, 15 to 49 days), the 30-day incidence of ANC recovery was 97% (95% confidence interval [CI], 89% to 99%), the median time to achieve an unsupported platelet count >20 × 10/L was 26 days (range, 12 to 67 days), and the 60-day rate of platelet engraftment was 99% (95% CI, 89% to 100%). Cumulative incidence of full donor chimerism by day 100 was 88% (95% CI 79-90). Grade II-IV acute GVHD occurred in 35% of the patients (95% CI, 26% to 45%) at a median of 40 days (range, 23 to 166 days). The incidence of moderate to severe chronic GVHD was 5% (95% CI, 2% to 10%). No differences between the TBI and TMLI cohorts were seen in terms of engraftment, full donor chimerism, and GVHD. No organ toxicity was observed in the first months after transplantation in either cohort. The overall 2-year OS and PFS rates were 63%, and 54%, respectively, and were comparable in the 2 groups (P = .548). The strongest finding was that TBI can be safely replaced by TMLI in terms of engraftment, achievement of full donor chimerism status, GVHD incidence, and extrahematologic toxicities.
低剂量全身照射（TBI）在来自半相合供体（haplo-SCT）的异基因干细胞移植前的非清髓性预处理（NMAC）方案中已长期使用。最近，在预处理中使用全骨髓淋巴照射（TMLI）代替 TBI 的情况越来越多。本研究旨在评估一组接受低剂量 TMLI 治疗的患者在植入、完全供体嵌合状态、移植物抗宿主病（GVHD）和血液外毒性方面的结果，并将这些结果与接受常规包含 TBI 的预处理的患者进行比较。这项回顾性单中心研究纳入了 100 例接受半相合 SCT 的晚期血液系统恶性肿瘤患者。2009 年至 2011 年，NMAC 方案包括环磷酰胺、氟达拉滨和低剂量 TBI（2 Gy），2011 年后，TBI 被 TMLI（2 Gy）取代。患者接受移植后环磷酰胺、钙调磷酸酶抑制剂和霉酚酸酯预防 GVHD。对于所有患者，中性粒细胞绝对计数（ANC）恢复至>0.5×10/L 的中位时间为 21 天（范围 15 至 49 天），ANC 恢复的 30 天发生率为 97%（95%置信区间 [CI]，89%至 99%），达到无支持血小板计数>20×10/L 的中位时间为 26 天（范围 12 至 67 天），血小板植入的 60 天率为 99%（95%CI，89%至 100%）。第 100 天时完全供体嵌合的累积发生率为 88%（95%CI，79-90%）。在中位时间 40 天（范围 23 至 166 天）时，35%（95%CI，26%至 45%）的患者发生 II 级至 IV 级急性 GVHD。中度至重度慢性 GVHD 的发生率为 5%（95%CI，2%至 10%）。在植入、完全供体嵌合和 GVHD 方面，TBI 组和 TMLI 组之间没有差异。在两个队列中，在移植后的头几个月均未观察到器官毒性。两组的 2 年总生存率和无进展生存率分别为 63%和 54%，两组之间无差异（P=0.548）。最强的发现是，TBI 可以安全地被 TMLI 取代，在植入、达到完全供体嵌合状态、GVHD 发生率和血液外毒性方面均如此。
