HLA配型不合情况下造血干细胞移植的新方法

A novel approach to HLA-mismatched transplantation

目的 :采用新方法进行非体外去除T细胞的人类白细胞抗原 (humanleukocyteantigen ,HLA)配型不合造血干细胞移植。方法 :5 8例血液恶性肿瘤患者 ,33例为高危或难治复发白血病 ,接受了至少一个HLA位点不合的家庭供者造血干细胞移植。移植物为经粒细胞集落刺激因子 (granulocyteclony stimulatingfactor ,G CSF)动员的骨髓以及外周血造血干细胞 ,而无需体外去除T细胞。移植物抗宿主病 (graft versus host disease,GVHD)预防采用环孢菌素A +霉酚酸酯 +短程甲氨喋呤方案。结果 :所有患者均获得持久、完全供者植入。 5 8例患者中发生Ⅱ度及以上急性GVHD 2 2例 (37.9% ) ,其中Ⅲ度和Ⅳ度急性GVHD分别为 2例和 1例 ,其严重程度与HLA不合程度无相关 ;4 2例可评估患者中 ,慢性GVHD为 2 6例 (6 1.9% ) ,广泛型和局限型分别为 11例和 15例。复发 9例 ,除 1例外均为复发、难治白血病患者。死亡 14例 ,其中 7例死于疾病复发 ,另 7例死于移植相关合并症 ,其中严重感染和间质性肺炎各 2例 ,巨细胞病毒性脑炎、病毒型肝炎和急性GVHD死亡各 1例。中位随访 10月 (2～ 37.5月 ) ,5 8例患者中 4 2例无病存活 (disease freesurvival,DFS) ,高危患者 2年DFS明显低于标危患者 ,分别为 6 3.2 %和 77.6 % (P =0 .0 4 )。DFS与供受?

Objective: To investigate the new methods of human leukocyte antigen (HLA) mismatched transplantation in patients with hematologic malignancies. Methods: In this pilot study, 58 patients, 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with at least 1 of 6 loci mismatched. After conditioning, patients received non ex vivo, T-cell-depleted grafts of G-CSF-primed bone marrow plus G-CSF-mobilized peripheral blood stem cells, as well as graft-versus-host-disease (GVHD) prophylaxis. Results: All patients achieved sustained, full donor-type engraftment. The incidence of grades Ⅱ-Ⅳ acute GVHD was 37.9% (22 of 58), and grades Ⅲ and Ⅳ aGVHD developed in only 2 and 1 patients, respectively. Furthermore, there was no statistically significant association between the extents of HLA mismatching and the degree of aGVHD. Twenty-six of 42 (61.9%) evaluable patients had developed chronic GVHD (cGVHD) with limited cGVHD in 15. Nine patients relapsed, all but one with advanced or refractory leukemia. Fourteen patients died (24.1%),of whom 7 died of recurrent diseases and 7 of transplant-related complications (TRM): main causes of TRM were infection(2), intestinal pneumonia(2), CMV encephalitis(1), hepatitis(1) and aGVHD (1). Forty-four of the 58 patients (75.9%) survived and 42 (72.4%) were disease free with a median follow-up of 10 months (range, 2 to 37.5 months). The 2-year probabilities of disease-free survival for patients with standard and high risks were 77.6% and 63.2% respectively, which showed that high-risk disease status at transplantation was associated with worse disease-free survival (P=0.04). The degree of HLA mismatching between the donor and the recipient was not related to event-free survival (P=0.57), nor was cell number infused and aGVHD (P=0.78, 0.94 respectively). Conclusion: (1)HLA mismatched transplantation can be per formed without ex vivo T cell depletion. (2)Using G-CSF mobilized PBSCs as a source of stem cells may be possible and safe even in HLA mismatched transplantation.