Bruno Benedetto, Rotta Marcello, Patriarca Francesca, Mordini Nicola, Allione Bernardino, Carnevale-Schianca Fabrizio, Giaccone Luisa, Sorasio Roberto, Omedè Paola, Baldi Ileana, Bringhen Sara, Massaia Massimo, Aglietta Massimo, Levis Alessandro, Gallamini Andrea, Fanin Renato, Palumbo Antonio, Storb Rainer, Ciccone Giovannino, Boccadoro Mario
San Giovanni Battista Hospital, University of Turin, Turin, Italy.
N Engl J Med. 2007 Mar 15;356(11):1110-20. doi: 10.1056/NEJMoa065464.
In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of tandem autografts.
We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling. All patients were initially treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan and autologous stem-cell rescue. Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue. The primary end points were overall survival and event-free survival.
After a median follow-up of 45 months (range, 21 to 90), the median overall survival and event-free survival were longer in the 80 patients with HLA-identical siblings than in the 82 patients without HLA-identical siblings (80 months vs. 54 months, P=0.01; and 35 months vs. 29 months, P=0.02, respectively). Among patients who completed their assigned treatment protocols, treatment-related mortality did not differ significantly between the double-autologous-transplant group (46 patients) and the autograft-allograft group (58 patients, P=0.09), but disease-related mortality was significantly higher in the double-autologous-transplant group (43% vs. 7%, P<0.001). The cumulative incidence rates of grades II, III, and IV graft-versus-host disease (GVHD) combined and of grade IV GVHD in the autograft-allograft group were 43% and 4%, respectively. Overall, 21 of 58 patients (36%) were in complete remission after a median follow-up of 38 months (range, 10 to 72) after allografting. Of the 46 patients who received two autografts, 25 (54%) died.
Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem-cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of tandem stem-cell autografts. (ClinicalTrials.gov number, NCT00415987 [ClinicalTrials.gov].).
在这项针对新诊断的多发性骨髓瘤的治疗试验中，我们比较了一种方案，该方案包括造血干细胞自体移植，随后接受来自 HLA 匹配同胞的异基因移植，与串联自体移植方案。
我们连续招募了 162 例年龄在 65 岁及以下且至少有一个同胞的新诊断骨髓瘤患者。所有患者最初均接受长春新碱、阿霉素和地塞米松治疗，随后接受美法仑和自体干细胞救援。有 HLA 匹配同胞的患者随后接受非清髓性全身照射和来自同胞的干细胞。没有 HLA 匹配同胞的患者接受连续两次清髓剂量的美法仑，每次之后均进行自体干细胞救援。主要终点是总生存期和无事件生存期。
在中位随访 45 个月（范围 21 至 90 个月）后，80 例有 HLA 匹配同胞的患者的中位总生存期和无事件生存期长于 82 例无 HLA 匹配同胞的患者（分别为 80 个月对 54 个月，P = 0.01；35 个月对 29 个月，P = 0.02）。在完成指定治疗方案的患者中，双自体移植组（46 例患者）和自体移植 - 异基因移植组（58 例患者）的治疗相关死亡率无显著差异（P = 0.09），但双自体移植组的疾病相关死亡率显著更高（43% 对 7%，P < 0.001）。自体移植 - 异基因移植组中 II、III 和 IV 级移植物抗宿主病（GVHD）合并发生率和 IV 级 GVHD 的累积发生率分别为 43% 和 4%。总体而言，58 例患者中有 21 例（36%）在异基因移植后中位随访 38 个月（范围 10 至 72 个月）时达到完全缓解。在接受两次自体移植的 46 例患者中，25 例（54%）死亡。
在新诊断的骨髓瘤患者中，接受造血干细胞自体移植后再接受来自 HLA 匹配同胞的干细胞异基因移植的患者的生存期优于接受串联干细胞自体移植的患者。（ClinicalTrials.gov 编号，NCT00415987 [ClinicalTrials.gov]。）
