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
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Biol Blood Marrow Transplant. 2008 Nov;14(11):1288-97. doi: 10.1016/j.bbmt.2008.09.001.
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.
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。
