Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo
Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo
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DOI：
10.1182/blood-2008-07-167379
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发表时间：
2009-04-02
期刊：
影响因子：
20.3
通讯作者：
Boccadoro, Mario
中科院分区：
文献类型：
--
作者：
Bruno, Benedetto;Rotta, Marcello;Boccadoro, Mario
尽管最近取得了进展，同种异体移植仍然是骨髓瘤唯一可能的治愈方法。从1999年7月到2005年6月，100名年龄小于65岁的新诊断患者被纳入了一项前瞻性多中心研究。一线治疗包括以长春新素、阿霉素和地塞米松（VAD）为基础的诱导化疗，细胞减原性自体移植（melphalan 200 mg/m(2)），随后进行单剂量非清髓性全身照射和来自人类白细胞抗原（HLA）相同同胞的同种异体移植。主要终点是诊断后的总生存期（OS）和无事件生存期（EFS）。中位随访5年后，未达到OS， EFS为37个月。急性和慢性移植物抗宿主病（GVHD）的发生率分别为38%和50%。53%的患者达到完全缓解（CR）。同种异体移植前深度细胞减少（CR或非常好的部分缓解）与移植后CR的实现相关（风险比[HR] 2.20, P = .03）和更长的EFS（风险比[HR] 0.33, P < .01）。相反，慢性GVHD的发展与CR或反应持续时间无关。这种串联移植方法可以延长患者的生存时间和长期的疾病控制，在同种异体移植时减少肿瘤负担。我们目前正在研究“新药”在增强移植前细胞减少和移植后移植物抗骨髓瘤效应中的作用，以进一步改善临床结果。(http://ClinicalTrials.gov; nct - 00702247。)(血。2009;113:3375 - 3382)
Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD) based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m(2)) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA) identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of "new drugs" in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.) (Blood. 2009;113:3375-3382)