Huang Xiao-Jun, Liu Dai-Hong, Liu Kai-Yan, Xu Lan-Ping, Chen Huan, Han Wei, Chen Yu-Hong, Zhang Xiao-Hui, Lu Dao-Pei
Institute of Hematology, Peking University, Beijing, People's Republic of China.
Biol Blood Marrow Transplant. 2009 Feb;15(2):257-65. doi: 10.1016/j.bbmt.2008.11.025.
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 granulocyte-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 [CI]: 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.
异基因造血干细胞移植（allo-HSCT）仍然是治愈急性白血病（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，我们开发了一种新的HLA不匹配/单倍型相同移植方法，无需体外T细胞清除（TCD）。该方法将粒细胞集落刺激因子（G-CSF）动员的骨髓和外周血与强化免疫抑制相结合。我们分析了250例连续接受AL患者的结果，这些患者通过我们的新移植方案接受了来自家庭供体的HLA-A、B和DR 1-3个不匹配位点的HLA不匹配/单倍型相同移植。249例患者实现了持续的完全供体嵌合。2-4级急性移植物抗宿主病（aGVHD）的发生率为45.8%，3级和4级的发生率为13.4%，这与HLA差异程度无关。在217例可评估患者中，慢性移植物抗宿主病（cGVHD）的累积发生率为53.9%，广泛cGVHD的累积发生率为22.6%。250例患者中有141例在中位随访1092天（范围：442-2437天）时无疾病复发存活。17例患者接受供体淋巴细胞输注（DLI）作为移植后复发的治疗，7例患者实现无白血病生存（LFS）。急性髓性白血病（AML）的3年LFS概率在标准风险组和高风险组中分别为70.7%和55.9%，急性淋巴细胞白血病（ALL）分别为59.7%和24.8%。高风险组中较低的LFS与急性白血病的诊断相关（P = 0.001，相对风险[RR]，95%置信区间[CI]：2.94[1.535-5.631]）以及3级和4级aGVHD的发生相关（P = 0.004）。未处理的血液和骨髓采集的HLA不匹配/单倍型相同HSCT是可行的。
