Malladi R K, Peniket A J, Littlewood T J, Towlson K E, Pearce R, Yin J, Cavenagh J D, Craddock C, Orchard K H, Olavarria E, McQuaker G, Collin M, Marks D I
Department of Haematology, John Radcliffe Hospital, Oxford, UK.
Bone Marrow Transplant. 2009 May;43(9):709-15. doi: 10.1038/bmt.2008.375. Epub 2008 Nov 24.
By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3-72 months) and 48 months (7-72 months), the 2- and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P=0.80) and 61 and 53%, respectively (P=0.85). The 2-year non-relapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P=0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P=0.28). Grades II-IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P=0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P=0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P=0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.
通过对英国血液与骨髓移植学会登记处的88例患者进行回顾性分析,我们通过比较接受阿仑单抗预处理与未接受阿仑单抗预处理的患者,研究了体内T细胞清除在成人急性髓系白血病(AML)的人类白细胞抗原(HLA)相合同胞减低强度预处理(RIC)同种异体移植中的作用。两组在移植时的年龄、性别、核型和疾病状态方面相当。中位随访时间分别为27个月(3 - 72个月)和48个月(7 - 72个月),接受或未接受阿仑单抗治疗的患者2年和5年总生存率分别为60%和60%(P = 0.80)以及61%和53%(P = 0.85)。接受阿仑单抗治疗的患者2年非复发死亡率为12%,未接受阿仑单抗治疗的患者为17%(P = 0.49)。接受阿仑单抗治疗的患者2年复发率为35%,未接受阿仑单抗治疗的患者为19%(P = 0.28)。未接受阿仑单抗治疗的患者中22%(8/37)发生了II - IV级急性移植物抗宿主病(GVHD),接受阿仑单抗治疗的患者为14%(7/51)(P = 0.25)。未接受阿仑单抗治疗的患者中47%(14/30)发生了广泛慢性GVHD,接受阿仑单抗治疗的患者为4%(2/45)(P = 0.001)。在可评估的患者中,接受阿仑单抗治疗的患者感染风险高于未接受阿仑单抗治疗的患者(分别为79%和57%,P = 0.02)。总之,阿仑单抗通过降低慢性GVHD具有有益作用,且不影响总生存率。在阿仑单抗被推荐作为AML的RIC同种异体移植的标准治疗方法之前,有必要进行进一步研究。