Takami Akiyoshi, Okumura Hirokazu, Yamazaki Hirohito, Kami Masahiro, Kim Song-Wong, Asakura Hidesaku, Endo Tomoyuki, Nishio Mitsuyuki, Minauchi Koichiro, Kumano Koki, Sugimori Naomi, Mori Shinichiro, Takemoto Yoshitada, Shimadoi Shigeru, Ozaki Jun, Takaue Yoichi, Nakao Shinji
Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.
Int J Hematol. 2005 Dec;82(5):449-55. doi: 10.1532/IJH97.05086.
To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
为了确定移植物抗宿主病（GVHD）的诱导是否能改善干细胞移植（SCT）后急性复发性白血病的预后，我们使用大剂量阿糖胞苷（ara-C），随后输注含有外周血干细胞的供体来源的 Buffy 层来治疗 12 例复发性白血病患者。对于首次供体淋巴细胞输注（DLI）后未发生 II 至 IV 级急性 GVHD 的患者，在 5 周的间隔内至少重复进行两次 DLI。4 例（33%）患者发生了 II 至 IV 级急性 GVHD。3 例患者发生了慢性 GVHD，其中 2 例未经历急性 GVHD。在 DLI 后发生 II 至 IV 级急性和/或慢性 GVHD 的 6 例患者中，4 例（67%）有反应，但其他 6 例患者均无反应。4 例（33%）患者（2 例急性髓性白血病[AML]和 2 例急性淋巴细胞白血病[ALL]）在首次 DLI 后实现了持续超过 4 个月的完全缓解，但其中 3 例在骨髓部位复发。在这 4 例患者中，1 例 AML 患者和 2 例 ALL 患者在 DLI 后 8 至 27 个月存活。这些发现表明，当诱导 GVHD 时，大剂量 ara-C 联合大剂量 DLI 可能使 SCT 后复发的急性白血病产生持久缓解。GVHD 的低诱导率以及 DLI 实现缓解后髓外复发是有待解决的问题。
