2016年02月15日,仇惠英教授课题组在美国权威期刊American Journal ofTranslational Research以研究论文的形式在线发表了关于异基因造血干细胞移植(Allo-HSCT)后巨细胞病毒(CMV)再激活与急性髓系白血病(AML)预后的相关性成果“Cytomegalovirus induces strong antileukemiceffect in acute myeloid leukemia patients following sibling HSCT withoutATG-containing regimen.”。CMV为Allo-HSCT后常见早期感染并发症,一旦出现CMV病,死亡率极高。近年来随着pp65及DNA等检测手段的开展,抢先抗CMV病毒治疗策略的普及,显著降低了移植后CMV再激活相关死亡率。该研究应用Gray test、Fineand Gray competing risk regression model等方法,对异基因移植后CMV再激活与AML预后进行了深入分析。研究发现未采用抗胸腺细胞球蛋白(ATG)的同胞人白细胞抗原(HLA)全相合异基因造血干细胞移植(Sib-HSCT)中,CMV复燃具有独特的临床特征,可显著降低AML复发率并改善总生存。该机制主要与CMV再激活可诱导供体的NK细胞及T淋巴细胞活性,进而增强供体抗白血病(GVL)效应。
近年来,在吴德沛教授带领下,不仅在细胞遗传学、血栓与止血等我院传统血液病学优势领域得到持续发展,更走出了具有苏大附一院血液科特色的骨髓移植中心路线。本研究主要显示了血液科骨髓移植中心在移植后病毒感染的临床研究达到了一个新的水平,实现了从降低CMV相关移植死亡率到CMV增强供体GVL效应的跨越;完成利弊转变及临床转化,使部分病人获益。该项研究得到了国家自然科学基金、江苏省高校优势学科、血液学协同创新中心等多项经费支持。
原文摘要:A considerable number of studies have demonstrated that cytomegalovirus(CMV) reactivation after allogeneic hematopoietic stem cell transplantation(Allo-HSCT) could enforce graft-versus leukemia (GVL) effect in acute myeloidleukemia (AML) patients. However, the use of antithymocyte globulin (ATG) aspart of graft-versus-host disease (GVHD) prophylaxis may dampen this beneficialeffect of CMV replication. In this context, we retrospectively analyzed theeffect of CMV reactivation on relapse, survival and prognosis in a total of 227AML patients who received a myeloablative (MA) conditioning regimen at a singleresearch center between January 2010 and April 2013. Of these 227 patients, 110cases received non-ATG-containing regimens and 117 cases receivedATG-containing regimens. CMV reactivation occurred in 45 patients (41%) amongnon-ATG regimen group and 73 patients (62%) among ATG regimen group (P =0.001). At a median time to follow-up of 27.5 months, a lower risk ofcumulative relapse incidence associated with CMV reactivation was observed innon-ATG group in multivariate analyses (OR 0.28, 95% CI 0.10-0.79; P = 0.016).However, CMV reactivation after transplantation did not significantly decreasethe cumulative incidence of relapse in our ATG group (OR 0.28, 95% CI0.10-0.79; P = 0.016). Collectively, our results demonstrate that in AMLpatients following sibling HSCT, the CMV-induced beneficial effect on relapseoccurs only in the MA regimens containing no ATG, although ATG promotes CMVreactivation.