Lekakis L, Giralt S, Couriel D, Shpall E J, Hosing C, Khouri I F, Anderlini P, Korbling M, Martin T, Champlin R E, de Lima M
Department of Blood and Marrow Transplantation, UT MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Bone Marrow Transplant. 2006 Sep;38(6):421-6. doi: 10.1038/sj.bmt.1705467. Epub 2006 Aug 7.
Cell dose is a critical determinant of outcomes in unrelated cord blood (CB) transplantation. We investigated a strategy in which CB units should contain at least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second unit had to be added. We report the results of a study that was prematurely closed owing to toxicity. Patients with advanced hematologic malignancies without a human leukocyte antigen-matched sibling or unrelated donor were eligible. Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three patients received double CB transplants. The 100-day and 1-year treatment-related mortality rates were 40 and 53%, respectively. Median time to neutrophil and platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One patient had secondary graft failure and five patients failed to engraft. Two patients are alive and disease free; 4-year actuarial survival is 33 versus 0% for patients transplanted in remission versus in relapse. We concluded that disease status was the main determinant of treatment failure in this study.
细胞剂量是无关供者脐血（CB）移植结局的关键决定因素。我们研究了一种策略，即CB单位应包含至少2×10⁷个总核细胞/千克受者体重，否则必须添加第二个单位。我们报告了一项因毒性而提前终止的研究结果。患有晚期血液系统恶性肿瘤且无人类白细胞抗原匹配同胞或无关供者的患者符合条件。预处理方案包括氟达拉滨和12 Gy全身照射（n = 11），或美法仑（n = 4），联合抗胸腺细胞球蛋白。移植物抗宿主病预防采用他克莫司和甲氨蝶呤。15例急性白血病（n = 9）、慢性粒细胞白血病（n = 2）、多发性骨髓瘤（n = 2）和淋巴瘤（n = 2）患者接受了治疗；60%的患者在移植时疾病复发。3例患者接受了双份CB移植。100天和1年的治疗相关死亡率分别为40%和53%。中性粒细胞和血小板植入的中位时间分别为22天（n = 10）和37天（n = 10）。1例患者发生继发性移植失败，5例患者未植入。2例患者存活且无疾病；缓解期移植患者的4年精算生存率为33%，而复发期移植患者为0%。我们得出结论，在本研究中疾病状态是治疗失败的主要决定因素。
