摘要
目的观察和比较亲属间人类白细胞抗原（HLA）单倍体相合与全相合外周血造血干细胞移植（PBSCT）治疗恶性血液病的临床疗效。方法2004年5月至2009年2月，共111例恶性血液病患者进行了异基因PBsCT（allo-PBSCT），其中单倍体相合移植受者51例（单倍体组），同期全相合移植受者60例（全相合组）。两组的预处理方案均为清髓性；两组预防移植物抗宿主病（GVHD）均以经典环孢素A加短程甲氨蝶呤作为基础方案，HLA1个抗原不合时，加用吗替麦考酚酯，HLA2～3个抗原不合时，再加用抗胸腺细胞球蛋白（ATG）及抗CD25单克隆抗体。移植物为经粒细胞集落刺激因子动员的、未进行体外去除T淋巴细胞的外周血造血干细胞（PBSC）。结果111例受者均获得完全、持久供者干细胞植入。单倍体组和全相合组受者中性粒细胞≥0．5×10^9／L的中位时间分别为14d和12d，血小板≥20×10^9／L的中位时间分别为15d和13d。单倍体组有25例受者发生急性GVHD（aGVHD），其中I度20例，Ⅱ度5例；有33例发生慢性GVHD（cGVHD），其中局限型30例，广泛型3例；4年累积发病率为70．4％；无白血病存活40例，3年预期总无白血病存活率（LFS）为74．5％，其中标危型77．3％，高危型68．2％。全相合组有14例发生aGVHD，其中I度10例，Ⅱ度2例，Ⅲ度2例；有37例发生cGVHD，其中局限型32例，广泛型5例；4年累积发病率为58．1％。无白血病存活46例，3年预期总LFS为72．1％，其中标危型77．6％，高危型52．7％。单倍体组受者移植后aGVHD发生率高于全相合组，差异有统计学意义（P〈0．05）；但cGVHD、原发病复发率和LFS差异均无统计学意义（P〉0．05）。结论应用清髓性预处理联合多种免疫抑制剂进行非体外去T淋巴细胞的、亲属间HLA单倍体相合与全相合PBSCT均为治疗恶性血液病安全有效的方案。
Objective To explore the clinical outcome of HLA haploidentical vs HLA-matehed peripheral blood hematopoietic stem cell transplantation （PBSCT） without in vitro T-cell depletion for malignant hematological diseases. Methods 111 patients with malignant hematological diseases underwent PBSCT without in vitro T-cell depletion between May 2004 and February 2009, including 51 patients with HLA-haploidentical and 60 patients with HLA-matched. All patients have received myeloablative conditioning regimen. A two-agent based graft-versus-host disease （GVHD） prophylaxis was used as cyclosporine A and a short course of methotrexate. Mycophenolate mofetile was added for the patients with one locus mismatch. Mycophenolate mofetile, antithymocyte globulin and CD25 monoelonal antibody were added for the patients with 2-3 loci mismatch. The grafts were granulocyte colony-stimulating factor-mobilized peripheral blood stem cells without in vitro T-cell depletion. Results 111 patients achieved sustained and full donor-type engraftment. The median time to reach an absolute neutrophil count above 0. 5 × 10^9/L was 14 days and that to a platelet count exceeding 20× 10^9/L was 15 days in 51 HLA-haploidentical patients, and that was 12 days and 13 days in 60 HLA-matched patients, respectively. In 51 HLA-haploidentical patients, 25 patients developed aGVHD, including 20 cases of grade I aGVHD, and 5 cases of grade lI. Thirty-three patients developed cGVHD with limited in 30 and extensive in 3. The 4-year cumulative incidence of cGVHD was 70. 4 %. The 3-year probabilities of leukemia-free survival （LFS） were 74. 5% （77. 3 % for standard risk patients and 68. 2 % for high risk patients respectively）. Seven patients had recurrence. In 60 HLA-matched patients, 14 patients developed aGVHD, including 10 cases of grade I , 2 cases of grade H and 2 cases of grade III. Thirty-seven patients developed cGVHD with limited in 32 and extensive in 5. The 4 year cumulative incidence of cGVHD was 58. 1%. The 3 year probabilities of LFS were 72. 1% （77. 6% for standard risk patients and 52. 7 % for high risk patients respectively）. Ten patients had recurrence. The incidence of aGVHD in HLA-haploidentical cohort was significantly higher than in HLA-matched cohort （P〈0. 05）. There was no significant difference in incidence of cGVHD, incidence of relapse and LFS between HLA-haploidentical and HLA-matched cohorts （P 〈 0. 05 ）. Conclusion Haploidentical PB,SCT is feasible and safe for malignant hematological diseases to use myeloablative conditioning regimen in combination with intensive immunosuppressants without in vitro T cell depletion.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2010年第2期79-83,共5页
Chinese Journal of Organ Transplantation
基金
新疆维吾尔自治区高技术研究与发展计划项目（200511109）
关键词
外周血干细胞移植
HLA抗原
恶性血液病
Peripheral blood stem cell transptantation
HLA antigens
Hematologic malignancies
