Soiffer R J, Fairclough D, Robertson M, Alyea E, Anderson K, Freedman A, Bartlett-Pandite L, Fisher D, Schlossman R L, Stone R, Murray C, Freeman A, Marcus K, Mauch P, Nadler L, Ritz J
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Blood. 1997 Apr 15;89(8):3039-47.
The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.
对于患有急性髓性白血病（AML）和急性淋巴细胞白血病（ALL）的成年患者，骨髓移植（BMT）的合适时机存在争议。尽管异基因移植比单纯强化化疗导致疾病复发的风险更低，但由于治疗相关致命并发症的发生率较高，BMT后的总体结局可能并未得到改善，这些并发症通常是移植物抗宿主病（GVHD）发展的结果。供体骨髓的选择性T细胞清除可降低GVHD的发生率，从而限制移植相关毒性。在此我们报告了接受CD6清除的异基因骨髓进行BMT的初治急性白血病成年患者的GVHD风险、移植相关死亡率（TRM）、疾病复发可能性及总生存率。使用T12单克隆抗体和补体从供体骨髓中清除CD6 + T细胞，对41例具有急性白血病和高危特征（28例AML，13例ALL）的患者连续进行了异基因移植。未给予移植前或移植后预防GVHD的免疫抑制药物。接受HLA匹配移植物的患者发生2至4级急性GVHD的精算估计风险为15%。5例患者发生了慢性GVHD。初治完全缓解患者在第100天和2年时TRM的估计风险分别为5%和16%。仅3例患者死于巨细胞病毒或EB病毒感染。4年时复发、总生存和无事件生存的估计概率分别为25%、71%和63%。与ALL患者相比，AML患者在GVHD、TRM、复发率或生存率方面未观察到显著差异。使用CD6清除的骨髓进行异基因移植可有效巩固初治高危急性白血病患者的缓解，且无过度毒性。
