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采用阿仑单抗的减低强度异基因移植,供者为 HLA 匹配的亲缘、非亲缘或单倍体相合亲缘供者,用于血液系统恶性肿瘤患者。

Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.

机构信息

Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.

出版信息

Biol Blood Marrow Transplant. 2014 Feb;20(2):257-63. doi: 10.1016/j.bbmt.2013.11.010. Epub 2013 Nov 20.

Abstract

We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.

摘要

我们对 124 例接受低强度预处理后接受 HLA 匹配的亲缘供者(MRD)、HLA 匹配的无关供者(MUD)或 HLA 半相合亲缘供者(HAPLO)移植的血液系统恶性肿瘤患者进行了一项比较研究。预处理方案包括氟达拉滨、马法兰或白消安联合阿仑单抗,用于治疗淋巴细胞性疾病(n=62)或髓系疾病(n=62)。霉酚酸酯用于预防移植物抗宿主病(GVHD),分别有 38、58 和 33 例患者接受了来自 MRD、MUD 和 HAPLO 供者的移植。只有 2 例患者在接受马法兰方案后发生原发性移植物失败(GF),而接受白消安方案后 17 例 HAPLO 供者移植的患者中有 8 例发生原发性 GF。接受 MRD、MUD 或 HAPLO 供者移植的患者发生 3 级至 4 级急性 GVHD 的累积发生率分别为 3%、11%和 27%,2 年总生存率(OS)分别为 51%、22%和 23%。多因素分析显示,与 MRD 相比,来自 MUD 或 HAPLO 供者的移植是影响 OS 的不良因素(P=0.006 和 P=0.002)。总之,包含氟达拉滨、白消安或马法兰和阿仑单抗,仅用霉酚酸酯作为 GVHD 预防的低强度方案在 MRD 组中带来了有利的结果,但在 MUD 和 HAPLO 组中生存率较低。白消安方案导致 HAPLO 组原发性 GF 发生率较高,提示需要调整或强化免疫抑制。

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