异基因造血干细胞移植治疗重型β珠蛋白生成障碍性贫血

Allogeneic hematopoietic stem cell transplantation in 24 patients with β-thalassemia major

目的探讨异基因造血干细胞移植（allo-HsCT）治疗重型β珠蛋白生成障碍性贫血的临床疗效。方法PesaroⅡ—Ⅲ度重型8珠蛋白生成障碍性贫血患者24例接受allo-HSCT治疗，其中男性18例，女性6例，患者年龄中位数为4岁（2～15岁）。24例中，同胞供者23例，母亲供者1例；HLA6个抗原全相合23例，5个抗原相合1例；骨髓混合外周血干细胞移植15例，脐带血移植9例。采用白消安＋环磷酰胺＋氟达拉滨的预处理方案。环孢素A（CsA）＋甲氨蝶呤（MTX）＋抗胸腺细胞球蛋白（ATG）＋吗替麦考酚酯（MMF）联用预防移植物抗宿主病（GVHD）。中位随访时间13个月（3-69个月）。结果移植后22例患者造血功能顺利恢复。至随访结束，无病存活21例；移植相关死亡1例（4．2％）；移植物排斥反应2例（8．3％）。21例的3年无病存活率为87．5％，3年总体存活率为91．7％。Ⅱ-Ⅳ度急性GVHD的累积发生率为16．7％，慢性GVHD的累积发生率为20．3％，广泛性慢性GVHD的发生率为5．0％。结论异基因骨髓混合外周血干细胞移植治疗珠蛋白生成障碍性贫血可获得确切疗效，同时脐带血是珠蛋白生成障碍性贫血移植的重要干细胞来源。CsA＋MTX＋ATG＋小剂量、短疗程MMF的方案可以有效地减少严重急性GVHD的发生，提高移植疗效。

Objective To investigate the effect of allgeneic hematopoietic stem cell transplantation （allo-HSCT） for β-thalassemia major. Methods Twenty-four β-thalassemia major patients with median age of 4 years （range： 2-15 years）, 18 boys and 6 girls, received allo-HSCT. They were classified into class Ⅱ-Ⅲ according to Pesaro thalassemia classification. Twenty-three transplantations were from sibling donor and 1 was from mother, either HLA-identical （n = 23） or HLA-mismatched （5/6） （n = 1）. Fifteen patients received bone marrow transplantation （BMT） plus peripheral blood stem cell transplantation （PBSCT）, and 9 were subjected to umbilical cord blood transplantation （UCBT）. The conditioning regimen consisted of busalphan, cyclophosphamide, fludarabine, plus hydroxyurea before transplantation. Graft-versus-host disease （GVHD） prophylaxis included CsA, methotrexate, antilymphpcute globulin, and mycophenolate mofetil. The median follow-up period was 13 months （range： 3 - 69）. Results Of 24 patients, there were 21 cases （87. 5 %） of disease-free survival, 1 （4. 2 %） transplantation-related death, and 2 cases （8.3 %） of rejection. Three-year overall survival and disease-free survival rate was 91.7 % and 87. 5 % respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was 16. 7 and 20. 3 %, particularly cumulative extensive chronic GVHD was 5.0 %. Conclusion The sibling donor BMT plus PBSCT is an effective and safe way to treat β-thalassemia major. Cord blood is an important source of hematopoietic stern cells for HSCT. The protocol GVHD prophylaxis of CsA, MTX, ATG with a low-dose and short course of MMF can effectively reduce the incidence of severe acute GVHD, improve the outcome of thalassemia transplantation.