Craddock C, Szydlo R M, Dazzi F, Olavarria E, Cwynarski K, Yong A, Brookes P, de la Fuente J, Kanfer E, Apperley J F, Goldman J M
Department of Haematology, Hammersmith Hospital and Imperial College School of Medicine, London, UK.
Br J Haematol. 2001 Jan;112(1):228-36. doi: 10.1046/j.1365-2141.2001.02519.x.
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after haematopoietic stem cell transplantation from matched unrelated donors (MUD). The role of T-cell depletion (TCD) as a strategy to prevent GVHD is controversial because of the associated increased risk of leukaemic relapse, graft failure and delayed immune reconstitution. The demonstration that donor lymphocyte infusion (DLI) is effective salvage therapy if patients relapse after transplantation for chronic myeloid leukaemia (CML) prompted us to examine the proposal that TCD may be a form of GVHD prophylaxis particularly suited to this disease in patients undergoing MUD transplantation. We analysed the outcome of 106 consecutive patients with CML in first chronic phase who underwent MUD transplantation. Patients were conditioned with cyclophosphamide and total body irradiation (TBI), and received in vivo TCD, using CD52 monoclonal antibody, as GVHD prophylaxis. Donor lymphocytes were infused at the time of leukaemic relapse. The projected survival at 5 years for all patients was 52.6%. The probability of developing severe acute GVHD (grade 3 or 4) was 14.5%. The only significant predictor of overall survival in univariate and multivariate analysis was patient cytomegalovirus (CMV) serostatus: in CMV-negative patients survival at 5 years was 60% vs. 42% in CMV-positive patients (P = 0.006). The use of TCD was associated with an increased risk of relapse (62% probability at 5 years after transplant), but 80% of patients who received DLI achieved molecular remission that was durable in all but two cases. In vivo TCD, in conjunction with DLI at relapse, is a valuable GVHD prophylactic regimen in CMV-seronegative recipients of MUD allografts, but in CMV-seropositive patients this approach is associated with an increased non-relapse mortality. Consequently, GVHD prophylactic regimens in MUD transplantation should be tailored according to the patient and donor pretransplant characteristics.
移植物抗宿主病（GVHD）仍然是来自匹配无关供体（MUD）的造血干细胞移植后发病和死亡的主要原因。T细胞去除（TCD）作为预防GVHD的一种策略，其作用存在争议，因为这会增加白血病复发、移植物失败和免疫重建延迟的风险。有证据表明，如果慢性粒细胞白血病（CML）患者移植后复发，供体淋巴细胞输注（DLI）是有效的挽救治疗方法，这促使我们研究TCD可能是一种特别适合接受MUD移植的CML患者预防GVHD的形式这一观点。我们分析了106例连续的处于慢性期的CML患者接受MUD移植的结果。患者接受环磷酰胺和全身照射（TBI）预处理，并使用CD52单克隆抗体进行体内TCD，作为GVHD预防措施。在白血病复发时输注供体淋巴细胞。所有患者预计5年生存率为52.6%。发生严重急性GVHD（3级或4级）的概率为14.5%。单因素和多因素分析中总体生存的唯一显著预测因素是患者的巨细胞病毒（CMV）血清学状态：CMV阴性患者5年生存率为60%，而CMV阳性患者为42%（P = 0.006）。使用TCD与复发风险增加相关（移植后5年复发概率为62%），但接受DLI的患者中有80%实现了分子缓解，除两例外均持久。体内TCD联合复发时的DLI，对于MUD同种异体移植的CMV血清阴性受者是一种有价值的GVHD预防方案，但对于CMV血清阳性患者，这种方法会增加非复发死亡率。因此，MUD移植中的GVHD预防方案应根据患者和供体移植前特征进行调整。
