Treatment of Acute Leukemia with Unmanipulated HLA-Mismatched/Haploidentical Blood and Bone Marrow Transplantation
Treatment of Acute Leukemia with Unmanipulated HLA-Mismatched/Haploidentical Blood and Bone Marrow Transplantation
复制标题
使用未操作的 HLA 不匹配/半相合血液和骨髓移植治疗急性白血病。
DOI：
10.1016/j.bbmt.2008.11.025
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发表时间：
2009-02-01
影响因子：
4.3
通讯作者：
Lu, Dao-Pei
中科院分区：
文献类型：
--
作者：
Huang, Xiao-Jun;Liu, Dai-Hong;Lu, Dao-Pei
异基因造血干细胞移植（allo-HSCT）仍然是治疗急性白血病（AL）的最佳治疗选择之一。然而，许多患者没有人类白细胞抗原（HLA）匹配的供体。最近，我们开发了一种无需体外 T 细胞耗竭 (TCD) 的 HLA 错配/半相合移植新方法。该方法将粒细胞集落刺激因子（G-CSF）引发的骨髓和外周血与强化免疫抑制相结合。我们分析了 250 名连续 AL 患者的结果，这些患者通过我们的新移植方案接受了 HLA 不匹配/半相合移植，其中 HLA-A、B 和 DR 的 1-3 个不匹配位点来自家庭捐赠者。 249 名患者实现了持续、完全的供体嵌合。 2~4级急性移植物抗宿主病（aGVHD）发生率为45.8%，3、4级发生率为13.4%，与HLA差异程度无关。在217名可评估患者中，慢性GVHD（cGVHD）的累积发生率为53.9%，广泛cGVHD的累积发生率为22.6%。在中位随访 1092 天（范围：442-2437 天）时，250 名患者中有 141 名未出现疾病复发。 17 名患者接受 DLI 作为移植后复发的治疗方法，7 名患者实现了无白血病生存 (LFS)。在标准风险组和高风险组中，急性髓性白血病（AML）的 3 年 LFS 概率分别为 70.7% 和 55.9%，急性淋巴细胞白血病（ALL）的 3 年概率分别为 59.7% 和 24.8%。较低的 LFS 与高危组中急性白血病的诊断（P = 0.001，相对风险 [RR]，95% 置信区间 [Cl]：2.94[1.535-5.631]）以及 3 级和 4 级 aGVHD 的发生相关（P = 0.004）。 HLA 不匹配/半相合 HSCT 对于未经处理的血液和骨髓采集是可行的。
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulotyce-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P =.001, relative risk [RR], 95% confidence interval [Cl]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P =.004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest.