无关供体造血干细胞移植治疗46例儿童难治性白血病疗效分析

Outcome of 46 children with refractory leukemia treated with unrelated donor hematopoietic stem cell transplantation

目的评估无关供体造血干细胞移植（UDT）治疗儿童难治性白血病的疗效。方法回顾性分析连续在我院接受UDT的46例白血病患儿的临床资料。急性淋巴细胞性白血病（ALL）患儿接受全身放疗为主的预处理、急性髓细胞性白血病（AML）和慢性粒细胞性白血病（CML）患儿采用白消安清髓。结果中位年龄8．0（2—17）岁，3年总存活率（0s）63．0％，23．9％患儿死于移植相关并发症，13．0％患儿死于白血病复发。移植过程中33．3％出现Ⅲ～Ⅳ度急性移植物抗宿主病（aGVHD），55．6％发生慢性移植物抗宿主病（GVHD）（13．9％为慢性广泛性GVHD）。大于10岁、小于10岁患儿的0S差异有统计学意义（45．0％掷．76．9％，P=0．015）；ALL患儿3年0s明显差于CML和AML（38，4％、66．7％vs．80．0％，P=0．034）；高危白血病疗效明显差于低危患儿（45．8％VS．81．8％，P=0．012）；人类白细胞抗原（HLA）高分辨6／6全相合、1／6不合较2／6位点不合患儿的OS显著增高（75．0％，75．0％vs.16．7％，P=0．007）；移植中出现Ⅲ～Ⅳ度与0～Ⅱ度aGVHD患儿相比0s差异无统计学意义（66．0％vs．66．7％，P=0．494）。结论UDT治疗我国儿童难治性白血病疗效令人满意。小于10岁、HLA相合度高是UDT的有利因素，髓系、低危白血病疗效优于其他白血病。

Objective To evaluate the efficacy of matched unrelated donor hematopoietic stem cell transplantation （UDT） and influencing factors in children with refractory leukemia. Method Retrospective analysis was performed on clinical data of 46 consecutive children received UDT between Nov. 2002 and Dec. 2008. A 12-14 GY fractioned total body irradiation （TBI） was given to children with acute lymphoblastic leukemia （ALL）. Busulphan based myeloablative regimen was applied to all the other patients. ATG （Frescnius） 15-20 mg/kg ＋ low dose cyclosporine A oral [ CSA, 8-12 mg/（kg ·d） with serum trough levels 150-200 ng/ml] -＋ methotrexate （without methotrexate for cord blood transplant） were administered as graft versus host disease （GVHD） prophylaxis. Mycophenolate mofetil [ MMF, 20-30 mg/ （kg · d）] was added for 13 CML after Jan 1, 2006 because of more severe GVHD was observed in this group. Results The median age was 8. 0 （2-17）years with the median follow np period of 23. 5 （0. 7 -85 ） months. The estimated 3 years overall survival （OS） was 63.0% ; 23.9% patients died of transplant related mortality, 13.0% patients died of leukemia relapse. Cytomegalovirus （CMV） infection recurred in 50% patients and hemorrhagic cystitis in 15.2% patients; 33.3% patients developed grade IlI-1V acute GVHD and 55.6% developed chronic GVHD （13.9% with extensive chronic GVHD）. The OS was significantly different between the patients older （ n = 20 ） and younger （ n = 26 ） than 10 years （ 45.0% vs. 76. 9%, P = 0. 015） and among the patients with ALL （ n = 13 ）, CML （ n = 18 ） and AML （ n = 15 ） （ 38.4%, 66. 7% vs. 80.0% ,P =0. 034）. The OS in patient with high risk leukemia（n =24）was lower than that in the patient with low risk leukemia （n =22） （45.8% vs. 81.8% , P =0. 012）. Except 8 cord blood transplant the OS of patients with HLA 6/6 high resolution completely matched （n = 16） and 1/6 mismatched （n = 16）bone marrow and peripheral blood stem cell transplants was significantly higher than patients with 2/6 mismatched （n=6） UDT（75.0% ,75.0% vs. 16. 7% , P =0. 007）. But the OS was not significantly different between patients with grade 0-II acute GVHD and III-IV acute GVHD （60.0% vs. 66. 7%, P = 0.494）. Conclusion The outcome of UDT for Chinese children with refractory leukemia is encouraging. Patients younger than 10 years with 0-1/6 high resolution mismatched UDT had the best OS. The outcome of patients with myeloid and low risk leukemia is superior to those with other types of leukemia.