异基因造血干细胞移植治疗高危恶性血液病

目的 分析HLA配型相合同胞供者异基因造血干细胞移植（allo-HSCT）治疗高危恶性血液病的疗效及影响疗效的相关因素。方法 回顾性分析90例有高危因素的恶性血液病患者,其中急性髓细胞白血病（AML）43例,急性淋巴细胞性白血病（ALL）28例,急性混合细胞性白血病（AHL）2例;移植前处于第1次完全缓解期（CR1）11例,均为Ph染色体阳性,第二次及以上CR期23例,未缓解／复发39例;骨髓增生异常综合征（MDS）-难治性贫血伴原始细胞增多或难治性贫血伴原始细胞增多一转化型17例。预处理方案采用全身照射加环磷酰胺（CY／TBI）方案11例,白消安加环磷酰胺方案79例。干细胞来源包括骨髓移植（BMT）27例,外周血造血干细胞移植（PBSCT）30例,BMT＋PBSCT33例;移植物抗宿主病（GVHD）预防采用经典环孢素A加短程甲氨蝶呤（MTX）。平均随访时间为15个月。结果 至随访终点,62．2％（56／90）存活,55．5％（50／90）无病存活,31．1％（28／90）复发。HSCT后预计4年累积总体生存率（OS）为45．5％,无病生存率（DFS）为34．9％。移植前处于CR、未缓解／复发和MDS患者HSCT后4年的累积0s分别为54．0％、28．2％和70．1％（P=0．027）。发生0～Ⅰ和Ⅱ～Ⅳ度GVHD的患者HSCT后的4年OS分别为57．6％和26．7％（P=0．015）,而患者性别、年龄、移植前有无脑膜白血病、预处理方案、干细胞来源均不是OS,DFS及复发的影响因素。多因素分析表明,移植前处于CR期者长期生存率明显提高,而ALL长期生存率明显低于AML／MDS。结论 对有高危因素的血液系统恶性肿瘤患者,选择allo—HSCT可使部分患者延长无病生存乃至根治。移植前处于CR期者长期生存率明显提高,ALL复发率明显高于AML／MDS。对于急性白血病挽救性治疗争取在取得CR后移植;对于MDS患者一经诊断,无需化疗,可尽早移植。

Allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia

OBJECTIVE: To retrospectively analyze the results of a consecutive series of 90 refractory/relapsed acute leukemia (AL) patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our center. METHODS: Of the 90 refractory/relapsed AL patients, 56 were male and 34 female, with a median age of 37 (13 - 59) years. Among them, 73 patients suffered from AL including 11 Ph+ acute lymphoid leukemia in first complete remission, 23 in second or greater complete remission, 39 in non-remission or relapse and 17 patients suffered from myelodysplastic syndrome (MDS-RAEB or RAEB-T) before transplant. Allo-HSCT from HLA identical siblings was performed for all the patients, of whom 27 received bone marrow transplantation (BMT), 30 peripheral blood stem cell transplantation (PBSCT) and 33 BMT + PBSCT. Eleven patients underwent allo-HSCT with conditioning regimen of CY/TBI and 79 with BU/CY. CsA + MTX regimen was use for prophylaxis of graft-versus-host disease (GVHD). The average follow-up was 15 months. RESULTS: At the last follow-up, 56/90 (62.2%) survived, 50/90 (55.5%) survived without leukemia and 28/90 (31.1%) relapsed. The estimated 4-year overall survival (OS) and disease-free survival (DFS) of the 90 cases was 45.5% and 34.9%. The 4-year OS and DFS were significantly higher for patients in CR (54.0%) or MDS (70.1%) than in non-remission and relapsed (28.2%) patients before allo-HSCT (P = 0.027). The outcome of grade 0-I acute GVHD was better than that of II-IV GVHD (57.6% vs 26.7%, P = 0.015). Sex, age, central nervous system leukemia, conditioning regimen and the source of stem cell were not the factors affecting OS, DFS, cumulative incidences of relapse rate and treatment related mortality. Multivariate analysis showed the most significant factor associated with high DFS was the disease state. CONCLUSIONS: allo-HSCT can cure a significant proportion of refractory/relapsed AL patients, especially for those in CR. Early allo-HSCT is recommended for MDS patients.