自体骨髓混合HLA半相合异体骨髓移植治疗恶性血液病(英文)

Autologous Marrow Mixed with HLA Haplo-Identical Allogeneic Marrow Transplantation for Treatment of Hematopoietic Malignancies

为了博采异基因BMT的GVL效应与ABMT不受供者限制的优点,作者用小鼠同基因混合H-2半相合异体骨髓移植,证实二者在一定比例混合移植后能耐受GVHD的发生且具明显的GVL效应。本研究作者报告了临床自体骨髓混合HLA半相合异基因骨髓移植,同时在体外高热及液体培养净化联合IL-2激活骨髓细胞,移植后又注射IL-2,以提高体内外对残留肿瘤细胞的净化效应,减弱GVHD反应和增强GVL效应。观察证实:移植过程是安全的,16例中无一例发生急性GVHD;近期疗效较好,移植后16例中5例复发,复发率为31.3％;11例未复发,其中7例随访7个月仍存活或且CCR,最长1例已无病存活35个月,余4例死于并发症和其它非血液病;16例除1例因早期死于HVOD外,余皆成功造血重建;对存活6例供受者性别不同患者性染色体分析发现移植后3例形成嵌合体,最长者已11个月余,目前仍在观察中。这一研究为临床恶性血液病治疗提供了一个新的途径。

We previously demonstrated that syngeneic graft mixed with H-2 haplo-identical bone marrow transplantation could show not only protection against graft-versns-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In present paper, we report the clinical observations of using autologous marrow mixed with HLA haplo-identical allogeneic marrow transplantation for treatment of malignant blood diseases. 16 cases including 12 with acute leukemia and 4 with advanced malignant lymphoma were treated by autologous marrow purged in vitro by hyperthemia (42.5℃ for 70 min) following incubation for 5 days with interleukin 2 (IL-2) in liquid culture mixed with HLA haplo-identical marrow cells from their siblings or parents. Acute GVHO were not observed in all patients after transplantation. The hematological recovery in the clinical setting was demonstrated in all cases but one who died early from hepatic veno-occlusive disease (VOD). 5 cases transplanted at the time of CR2, CR3 or advanced phase of lymphoma, relapsed 4 or 7 months after transplantation with relapse rate of 31.3%. Particulary all 8 patients receiving allogeneic BMT in 2 hours after ABMT did not relapse; 2 of them died from related complications and 2 died from non-hematological diseases. 7 cases are still alive in disease-free survival with median follow-up of 12 months after treatment. The mixed chimerism was found in 3/6 cases who had different sex donors by chromosome analysis. These results show that mixed transplantation is safe, effective and a new approach for malignancy therapy. In order to detect the effects of GVL, studies in this respect are now in progress in our clinic.