Kataoka I, Kami M, Takahashi S, Kodera Y, Miyawaki S, Hirabayashi N, Okamoto S, Matsumoto N, Miyazaki Y, Morishita Y, Asai O, Maruta A, Yoshida T, Imamura M, Hamajima N, Matsuo K, Harada M, Mineishi S
Hematopoietic Stem Cell Transplant Unit, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
Bone Marrow Transplant. 2004 Oct;34(8):711-9. doi: 10.1038/sj.bmt.1704659.
Acute graft-versus-host disease (GVHD) increases post-transplant mortality and morbidity, but exerts a potent graft-versus-leukemia (GVL) effect. To clarify the impact of GVHD on outcome after transplant in aggressive diseases, patients with acute myeloid or lymphoblastic leukemia (AML, n = 366 or ALL, n = 255) in nonremission states, or chronic myelogenous leukemia (CML, n = 180) in accelerated phase (AP) or blastic crisis (BC), who received allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor between 1991 and 2000, were analyzed. Significant improvement in overall and disease-free survival (DFS) was detected with grade I acute GVHD in AML (P = 0.0002 for overall survival and 0.0009 for DFS, respectively) and in CML (P = 0.0256 and 0.0366, respectively), while the trend towards improved survival was observed in ALL. Relapse rate was lower in grade I acute GVHD than in grade II in all three diseases, suggesting that treatment for grade II GVHD may compromise the GVL effect associated with GVHD. Chronic GVHD was found to suppress relapse in CML and ALL, but not in AML, although no improvement in survival was observed in any disease category. Our results suggest that treatment for grade II acute GVHD may need to be attenuated in transplant for refractory leukemias.
急性移植物抗宿主病(GVHD)会增加移植后的死亡率和发病率,但具有强大的移植物抗白血病(GVL)效应。为了阐明GVHD对侵袭性疾病移植后结局的影响,我们分析了1991年至2000年间接受来自相关供体的异基因造血干细胞移植(HSCT)的患者,这些患者包括处于非缓解状态的急性髓性或淋巴细胞白血病(AML,n = 366或ALL,n = 255),或处于加速期(AP)或急变期(BC)的慢性髓性白血病(CML,n = 180)。在AML(总生存率P = 0.0002,无病生存率P = 0.0009)和CML(分别为P = 0.0256和0.0366)中,I级急性GVHD可使总生存率和无病生存率显著提高,而ALL中也观察到生存改善的趋势。在这三种疾病中,I级急性GVHD的复发率均低于II级,这表明II级GVHD的治疗可能会损害与GVHD相关的GVL效应。虽然在任何疾病类别中均未观察到生存率的改善,但发现慢性GVHD可抑制CML和ALL的复发,但对AML无效。我们的结果表明,对于难治性白血病的移植,II级急性GVHD的治疗可能需要减弱。