Miyao Kotaro, Kuwatsuka Yachiyo, Murata Makoto, Nagafuji Koji, Teshima Takanori, Takeuchi Yuki, Shiratori Souichi, Najima Yuho, Uchida Naoyuki, Tanaka Masatsugu, Sawa Masashi, Ota Shuichi, Fukuda Takahiro, Ozawa Yukiyasu, Kako Shinichi, Kawakita Toshiro, Ara Takahide, Tanaka Junji, Kanda Yoshinobu, Atsuta Yoshiko, Kanda Junya, Terakura Seitaro
Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
Transplant Cell Ther. 2022 Mar;28(3):153.e1-153.e11. doi: 10.1016/j.jtct.2021.12.009. Epub 2021 Dec 22.
Previous Japanese studies have shown that bone marrow transplantation (BMT) is associated with better survival compared with peripheral blood stem cell transplantation (PBSCT) from a matched related donor (MRD). PBSCT recipients have shown higher incidences of severe graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) compared with BMT recipients. In recent years, the efficacy and safety of antithymocyte globulin (ATG) for PBSCT recipients has been evaluated worldwide. In the present study, we aimed to compare BMT and PBSCT recipients to identify current improvements and unmet needs among MRD PBSCT recipients. In addition, we evaluated the impact of ATG administration on the outcomes of PBSCT recipients. We retrospectively analyzed patients age ≥16 years with acute leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia who underwent their first BMT or PBSCT from an MRD between 2009 and 2018 in Japan. A total of 3599 transplantations were performed (BMT, n = 1218; PBSCT without ATG [PBSCT-ATG(-)], n = 2288; PBSCT with ATG [PBSCT-ATG(+)], n = 93). The PBSCT-ATG(-) group had a higher NRM (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.08 to 1.57; P = .005) and lower overall survival (OS) (HR, 1.16; 95% CI, 1.04 to 1.30; P = .011) compared with the BMT group. Furthermore, the PBSCT-ATG(-) group had higher incidences of grade III-IV, stage 2-4 gut, high-risk, and steroid-refractory acute GVHD compared with the BMT group. Acute GVHD had a negative impact on NRM and OS. The PBSCT-ATG(-) group also was associated with an elevated risk of chronic GVHD (HR, 1.89; 95% CI, 1.24 to 2.57; P < .001) and extensive chronic GVHD (HR, 1.44; 95% CI, 1.23 to 1.68; P < .001). The incidences of acute GVHD, chronic GVHD, and NRM and chronic GVHD-free relapse-free survival rates were comparable between the PBSCT-ATG(+) and BMT groups. The OS of patients with acute GVHD was similar in the 3 donor groups. Patients treated with reduced-intensity conditioning in the PBSCT-ATG(+) group had a higher relapse rate and lower OS rate compared with those in the BMT group. In this Japanese cohort, standard calcineurin inhibitor-based GVHD prophylaxis was not sufficient for recipients of MRD PBSCT because of the high incidence of severe acute GVHD. Prophylactic ATG was found to be a promising strategy against GVHD.
先前的日本研究表明，与来自匹配相关供体（MRD）的外周血干细胞移植（PBSCT）相比，骨髓移植（BMT）与更好的生存率相关。与BMT受者相比，PBSCT受者出现严重移植物抗宿主病（GVHD）和非复发死亡率（NRM）的发生率更高。近年来，抗胸腺细胞球蛋白（ATG）用于PBSCT受者的疗效和安全性已在全球范围内得到评估。在本研究中，我们旨在比较BMT和PBSCT受者，以确定MRD PBSCT受者当前的改善情况和未满足的需求。此外，我们评估了ATG给药对PBSCT受者结局的影响。我们回顾性分析了2009年至2018年在日本接受首次来自MRD的BMT或PBSCT的年龄≥16岁的急性白血病、骨髓增生异常综合征或慢性粒细胞白血病患者。共进行了3599例移植（BMT，n = 1,218；无ATG的PBSCT [PBSCT-ATG(-)]，n = 2,288；有ATG的PBSCT [PBSCT-ATG(+)]，n = 93）。与BMT组相比，PBSCT-ATG(-)组的NRM更高（风险比[HR]，1.30；95%置信区间[CI]，1.08至1.57；P = 0.005），总生存期（OS）更低（HR，1.16；95%CI，1.04至1.30；P = 0.011）。此外，与BMT组相比，PBSCT-ATG(-)组III-IV级、2-4期肠道、高危和类固醇难治性急性GVHD的发生率更高。急性GVHD对NRM和OS有负面影响。PBSCT-ATG(-)组还与慢性GVHD风险升高（HR，1.89；95%CI，1.24至2.57；P < 0.001）和广泛慢性GVHD（HR，1.44；95%CI，1.23至1.68；P < 0.001）相关。PBSCT-ATG(+)组和BMT组之间急性GVHD、慢性GVHD、NRM的发生率以及无慢性GVHD无复发生存率相当。3个供体组中急性GVHD患者的OS相似。与BMT组相比，PBSCT-ATG(+)组接受减低强度预处理的患者复发率更高，OS率更低。在这个日本队列中，由于严重急性GVHD的发生率高，基于标准钙调神经磷酸酶抑制剂的GVHD预防对MRD PBSCT受者来说是不够的。预防性使用ATG被发现是一种有前景的抗GVHD策略。
