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使用阿仑单抗进行体内T细胞清除对慢性淋巴细胞白血病减低强度异基因造血细胞移植的影响。

The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia.

作者信息

Delgado Julio, Pillai Srinivas, Benjamin Reuben, Caballero Dolores, Martino Rodrigo, Nathwani Amit, Lovell Richard, Thomson Kirsty, Perez-Simon Jose A, Sureda Anna, Kottaridis Panagiotis, Vazquez Lourdes, Peggs Karl, Sierra Jorge, Milligan Donald, Mackinnon Stephen

机构信息

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

出版信息

Biol Blood Marrow Transplant. 2008 Nov;14(11):1288-97. doi: 10.1016/j.bbmt.2008.09.001.

Abstract

Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation is increasingly considered for patients with chronic lymphocytic leukemia (CLL). To investigate the impact of in vivo T cell depletion with alemtuzumab on the incidence of graft-versus-host disease (GVHD), nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), we retrospectively analyzed the outcomes of 62 consecutive CLL patients conditioned with fludarabine and melphalan at 4 institutions. For GVHD prophylaxis, 41 patients (cohort 1) received alemtuzumab and cyclosporin; and 21 patients (cohort 2) received cyclosporin plus methotrexate or mycophenolate. Donors were 50 siblings and 12 unrelated volunteers. Twenty-two (36%) patients received donor lymphocyte infusions (DLI), 20 (49%) from cohort 1 and 2 (10%) from cohort 2 (P=.002). Grade III-IV acute GVHD (aGVHD) was observed in 20% and 38% of patients from cohorts 1 and 2, respectively (P=.14). Extensive chronic GVHD (cGVHD) was observed in 10% and 48% of patients from cohorts 1 and 2, respectively (P=.03). There was a trend toward a higher viral infection rate in cohort 1 compared to cohort 2 (68% versus 43%, P=.062), but the incidence of cytomegalovirus (CMV) reactivation was not significantly different. The 3-year OS, PFS, NRM, and relapse rates were 65%, 39%, 28%, and 32%, respectively, for cohort 1; and 57%, 47%, 34%, and 20%, respectively, for cohort 2 (P=.629, P=.361, P=.735, and P=0.112, respectively). In conclusion, both methods of GVHD prophylaxis were equivalent in terms of survival. The administration of alemtuzumab led to reduced cGVHD, possibly improving quality of life.

摘要

对于慢性淋巴细胞白血病(CLL)患者,降低强度预处理(RIC)异基因造血细胞移植越来越受到关注。为了研究使用阿仑单抗进行体内T细胞清除对移植物抗宿主病(GVHD)发生率、非复发死亡率(NRM)、无进展生存期(PFS)和总生存期(OS)的影响,我们回顾性分析了4家机构62例连续接受氟达拉滨和马法兰预处理的CLL患者的治疗结果。对于GVHD预防,41例患者(队列1)接受阿仑单抗和环孢素;21例患者(队列2)接受环孢素加甲氨蝶呤或霉酚酸酯。供者为50名同胞和12名无关志愿者。22例(36%)患者接受了供者淋巴细胞输注(DLI),其中20例(49%)来自队列1,2例(10%)来自队列2(P=0.002)。队列1和队列2中分别有20%和38%的患者发生III-IV级急性GVHD(aGVHD)(P=0.14)。队列1和队列2中分别有10%和48%的患者发生广泛慢性GVHD(cGVHD)(P=0.03)。与队列2相比,队列1的病毒感染率有升高趋势(68%对43%,P=0.062),但巨细胞病毒(CMV)再激活的发生率无显著差异。队列1的3年总生存期、无进展生存期、非复发死亡率和复发率分别为65%、39%、28%和32%;队列2分别为57%、47%、34%和20%(P分别为0.629、0.361、0.735和0.112)。总之,两种GVHD预防方法在生存方面相当。阿仑单抗的使用导致cGVHD减少,可能改善了生活质量。

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