Balduzzi A, Gooley T, Anasetti C, Sanders J E, Martin P J, Petersdorf E W, Appelbaum F R, Buckner C D, Matthews D, Storb R, Sullivan K M, Hansen J A
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Blood. 1995 Oct 15;86(8):3247-56.
Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.
1985年6月至1993年4月期间，88名年龄在0.5至17岁（中位数为9岁）的儿童接受了非亲属供者骨髓移植，用于治疗慢性粒细胞白血病（CML；n = 16）、处于首次或第二次缓解期的急性淋巴细胞白血病（ALL；n = 15）或更晚期阶段（n = 28）、急性髓细胞白血病（AML；n = 13）或其他血液系统疾病（n = 16）。所有患者均接受环磷酰胺和全身照射预处理，并接受甲氨蝶呤和环孢素联合治疗以预防移植物抗宿主病（GVHD）。46名患者接受了来自HLA匹配供者的移植，42名患者接受了来自在一个HLA - A或B或D/DRB1位点存在轻微错配的供者的移植。CML患者的无病生存率和复发率的Kaplan - Meier估计值分别为75%和0%，首次或第二次缓解期的ALL患者为47%和20%，复发期或第三次缓解期的ALL患者为10%和60%，首次缓解期（n = 1）或更晚期疾病（n = 12）的AML患者为46%和46%，其他疾病患者为29%和69%。HLA差异与较低的无病生存率无显著相关性，但结果表明HLA匹配受者的复发更多，且错配受者的移植相关死亡率显著更高（51%对24%，P = 0.04）。大多数死亡是由于与急性或慢性GVHD相关的感染，且发生在移植后的头2年内。所有可评估患者均实现粒细胞植入。HLA匹配受者和HLA错配受者分别在移植后中位98天和103天无病出院，比例分别为63%和57%（P = 无显著差异[NS]）。II - IV级急性GVHD的发生率在HLA匹配受者中为83%，在HLA错配受者中为98%（P = 0.009）。慢性GVHD的发生率在HLA匹配受者中为60%，在HLA错配受者中为69%（P = NS）。33名存活患者中有11名（33%）发生了一种或多种晚期不良事件，如白内障、髋部或膝部骨坏死、限制性或阻塞性肺部疾病以及甲状腺功能减退。58%的存活患者停用了免疫抑制剂，包括所有存活超过3.2年的12名患者，他们的兰斯基或卡诺夫斯基评分均为100%。这些数据表明，来自完全或部分HLA匹配的非亲属供者的骨髓移植可以是治疗血液系统疾病儿童的有效疗法，且移植前疾病状态和移植后GVHD仍然是影响患者预后的重要因素。
