HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血

HLA haploidentical peripheral blood stem cells transplantation for β thalassemia major

目的探索HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血的可行性。方法16例Ⅲ度重型β地中海贫血患儿接受HLA单倍体相合外周血造血干细胞移植。预处理方案：2007年12月前采用A方案，即氟达拉滨（总量150mg／m^2）＋白消安（静脉，总量520mg／m^2）＋环磷酰胺（总量100mg／kg）＋抗胸腺细胞球蛋白（总量10mg／kg）＋全身照射（总量3Gy）；2007年12月后采用B方案，即氟达拉滨（总量240mg／m^2），不进行全身照射，其余同A方案。移植物抗宿主病（GVHD）预防采用环孢素＋甲氨蝶呤＋霉酚酸酯三联方案。结果16例患者中14例（87．5％）成功植活，中性粒细胞≥0．5×10^9／L的时间为移植后第10～17天，中位时间第13天；血小板≥20×10^9／L的时间为移植后第14～20天，中位时间第15天。植活的14例患者移植后第30天检测证实均为供者型完全嵌合状态。2例患者未能植入，其中1例于移植后第52天自体造血恢复。Ⅱ-Ⅳ度急性GVHD4例，其中皮肤Ⅱ度GVHD2例，皮肤Ⅲ度GVHD1例，肠道Ⅳ度急性GVHD1例，广泛型慢性GVHD1例。中位随访时间49个月，14例患者存活，其中13例无病存活。结论HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血，可以使多数患者获得长期稳定的植活，对于无全相合供者的患儿而言是一种可行的治疗选择，急慢性GVHD仍是影响长期生存率及生活质量的主要因素。

Objective To evaluate the feasibility of HLA haploidentical peripheral blood hematopoietic stem cell transplantation（PBSCT） for patients with β thalassemia major. Methods Sixteen patients with β thalassemia major received HLA haploidentieal PBSCT from parents. Two conditioning regimens were used. Regimen A was adopted before December 2007, which consisted of fludarbine （ total 150 mg/m2 ） , busulfex （total 520 mg/m2）, cyelophosphamide （CTX, total 100 mg/kg）, antithymocyte globulin （ATG, total 10 mg/kg） and total body irradiation of 3 Gy. Regimen B was adopted after December 2007, which consisted of fludarbine （total 240 mg/m2 ）, busulfex （ total 520 mg/m2 ）, CTX （ total 100 mg/kg）, and ATG（ total 10 mg/kg）. Combination of cyelosporin（ CsA）, methotrexate（MTX） and mycophenolate mofetil（MMF） were used for prophylaxis of graft-versus-host disease（GVHD）. Results Of 16 patients, 14 （ 87.5% ） had sustained engraftment. The median days of neutrophil exceeding 0. 5 × 10^9/L and platelet exceeding 20 x 109/L were 13 days （range 10- 17 days） and 15 days （range 14-20 days） after PBSCT, respectively. Complete chimerism was achieved in all the 14 patients at one month after PBSCT. One patient lost his graft with autologous reconstitution 52 days after transplantation. Four patients had grade Ⅱ - Ⅳ acute GVHD and one patient had chronic extensive GVHD. In the 49-month median follow-up duration, 13 of 16 patients were alive in disease-free situation. Conclusion HLA haploidentical PBSCT, which could provide stable and sustained engraftment for thalassemia major patients with no HLA identical donor, is a promising treatment strategy.