Centre for Clinical Haematology, Main Drive, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.
Haematologica. 2010 Jun;95(6):989-95. doi: 10.3324/haematol.2009.013920. Epub 2009 Nov 30.
Reduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown.
We have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months.
The 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001).
Disease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.
减强度预处理方案可使老年急性髓系白血病患者获得潜在的治愈性移植物抗白血病效应。尽管 T 细胞耗竭越来越多地用于降低移植物抗宿主病的风险，但它对移植后移植物抗白血病效应和长期结果的影响尚不清楚。
我们在 168 例采用阿仑单抗为基础的减强度预处理方案移植的急性髓系白血病患者中，对决定总体生存的移植前和移植后因素进行了特征描述，中位随访时间为 37 个月。
在 CR1 或 CR2/CR3 中移植的患者 3 年总体生存率分别为 50%（95%可信区间，38%至 62%）和 44%（95%可信区间，31%至 56%），而复发/难治性疾病患者的生存率分别为 15%（95%可信区间，2%至 36%）。多变量分析表明，移植时的状态（P=0.008）和表现细胞遗传学（P=0.01）均影响生存和疾病复发。移植后 21 天内环孢素 A（CsA）暴露增加与复发风险增加（P<0.0001）和总体生存率降低（P<0.0001）相关。
疾病分期、表现核型和移植后 CsA 暴露是接受 T 细胞耗竭减强度预处理同种异体移植治疗急性髓系白血病患者的重要预后预测因素。这些数据证实了在 T 细胞耗竭减强度预处理同种异体移植后急性髓系白血病中存在强烈的移植物抗白血病效应，并确定了 CsA 暴露是该环境下结局的可操纵决定因素。
