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美国血液与骨髓移植学会、欧洲血液与骨髓移植学会、血液与骨髓移植临床试验网络以及国际骨髓瘤工作组关于复发多发性骨髓瘤患者挽救性造血细胞移植的共识会议

American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma.

作者信息

Giralt Sergio, Garderet Laurent, Durie Brian, Cook Gordon, Gahrton Gosta, Bruno Benedetto, Hari Paremesweran, Lokhorst Henk, McCarthy Phillip, Krishnan Amrita, Sonneveld Pieter, Goldschmidt Harmut, Jagannath Sundar, Barlogie Bart, Mateos Maria, Gimsing Peter, Sezer Orhan, Mikhael Joseph, Lu Jin, Dimopoulos Meletios, Mazumder Amitabha, Palumbo Antonio, Abonour Rafat, Anderson Kenneth, Attal Michel, Blade Joan, Bird Jenny, Cavo Michele, Comenzo Raymond, de la Rubia Javier, Einsele Hermann, Garcia-Sanz Ramon, Hillengass Jens, Holstein Sarah, Johnsen Hans Erik, Joshua Douglas, Koehne Guenther, Kumar Shaji, Kyle Robert, Leleu Xavier, Lonial Sagar, Ludwig Heinz, Nahi Hareth, Nooka Anil, Orlowski Robert, Rajkumar Vincent, Reiman Anthony, Richardson Paul, Riva Eloisa, San Miguel Jesus, Turreson Ingemar, Usmani Saad, Vesole David, Bensinger William, Qazilbash Muzaffer, Efebera Yvonne, Mohty Mohamed, Gasparreto Christina, Gajewski James, LeMaistre Charles F, Bredeson Chris, Moreau Phillipe, Pasquini Marcelo, Kroeger Nicolaus, Stadtmauer Edward

机构信息

Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, New York.

Hospital St Antoine, INSERM UMR_S 938, Paris, France.

出版信息

Biol Blood Marrow Transplant. 2015 Dec;21(12):2039-2051. doi: 10.1016/j.bbmt.2015.09.016. Epub 2015 Sep 30.

Abstract

In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic HCT, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic HCT maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy.

摘要

与高剂量疗法联合自体造血细胞移植(HCT)作为多发性骨髓瘤(MM)患者首次缓解后的巩固治疗的前期情况不同,高剂量疗法联合自体或异基因HCT在初次治疗后复发的MM患者中的作用尚未得到广泛研究。国际骨髓瘤工作组与血液和骨髓移植临床试验网络、美国血液和骨髓移植学会以及欧洲血液和骨髓移植学会召集了一次MM专家会议,以:(1)总结目前关于自体或异基因HCT在初次治疗后病情进展的MM患者中的作用的知识;(2)提出MM挽救性HCT的使用指南;(3)确定知识空白;(4)提出研究议程;(5)制定一项合作计划以推进研究议程。在审查现有数据后,专家委员会就挽救性自体HCT达成了以下共识声明:(1)在初次治疗后复发且未接受自体HCT的适合移植的患者中,高剂量疗法联合HCT作为挽救治疗的一部分应被视为标准治疗;(2)对于初次治疗后复发且初次缓解持续时间超过18个月的接受过自体HCT的任何患者,高剂量疗法和自体HCT应被视为合适的治疗方法;(3)高剂量疗法和自体HCT可作为异基因HCT的桥接策略;(4)挽救性HCT维持治疗的作用需要在精心设计的前瞻性试验背景下进行探索,这些试验应包括新的药物,如单克隆抗体、免疫调节药物和口服蛋白酶体抑制剂;(5)自体HCT巩固治疗应作为一种策略进行探索,以开发针对初次治疗后缓解期短(少于18个月)的患者的新型预处理方案或HCT后策略;(6)需要进行前瞻性随机试验,以确定挽救性自体HCT在初次治疗后复发的MM患者中的作用,并将其与“最佳非HCT”治疗进行比较。专家委员会还强调了在疾病过程早期收集足够的造血干细胞以进行两次移植的重要性。关于异基因HCT,专家委员会达成了以下共识声明:(1)对于初次治疗后早期复发(少于24个月)且接受过自体HCT和/或具有高风险特征(即细胞遗传学、髓外疾病、浆细胞白血病或高乳酸脱氢酶)的任何符合条件的患者,异基因HCT应被视为合适的治疗方法;(2)如有可能,异基因HCT应在临床试验背景下进行;(3)异基因HCT后维持治疗的作用需要在精心设计的前瞻性试验背景下进行探索;(4)需要进行前瞻性随机试验,以确定挽救性异基因HCT在初次治疗后复发的MM患者中的作用。

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