Nishiwaki Satoshi, Sugiura Isamu, Sato Takahiko, Kobayashi Miki, Osaki Masahide, Sawa Masashi, Adachi Yoshitaka, Okabe Motohito, Saito Shigeki, Morishita Takanobu, Kohno Akio, Nishiyama Takahiro, Iida Hiroatsu, Kurahashi Shingo, Kuwatsuka Yachiyo, Sugiyama Daisuke, Ito Sachiko, Nishikawa Hiroyoshi, Kiyoi Hitoshi
Department of Advanced Medicine Nagoya University Hospital Nagoya Japan.
Division of Hematology and Oncology Toyohashi Municipal Hospital Toyohashi Japan.
EJHaem. 2023 Mar 20;4(2):358-369. doi: 10.1002/jha2.677. eCollection 2023 May.
Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto-PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34 cells was harvested in all five patients. No patient died within 100 days after auto-PBSCT, and no unexpected serious adverse events were observed. Although 1-year event-free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389-1088 days) after auto-PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto-PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto-PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long-term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long-term molecular remission.
自体造血干细胞移植（SCT）并非费城染色体阳性急性淋巴细胞白血病（Ph+ALL）的标准治疗选择；然而，自酪氨酸激酶抑制剂（TKIs）问世以来，其地位已被重新评估。我们前瞻性分析了自体外周血干细胞移植（auto-PBSCT）对年龄在55至70岁且已实现完全分子缓解的Ph+ALL患者的疗效和安全性。采用美法仑、环磷酰胺、依托泊苷和地塞米松进行预处理。共进行了12个疗程的维持治疗，包括达沙替尼。所有5例患者均采集到了所需数量的CD34细胞。auto-PBSCT后100天内无患者死亡，也未观察到意外的严重不良事件。尽管1年无事件生存率为100%，但3例患者在auto-PBSCT后中位801天（范围389 - 1088天）出现血液学复发。另外2例患者虽在最后一次随访时维持首次血液学缓解，但观察到分子进展性疾病。对于Ph+ALL患者，联合TKIs进行auto-PBSCT可安全实施。尽管单次治疗强度增加，但auto-PBSCT仍存在局限性。有必要制定包括新分子靶向药物的长期治疗策略以维持长期分子缓解。
