Klyuchnikov E, Bacher U, Kroll T, Shea T C, Lazarus H M, Bredeson C, Fenske T S
Department of Stem Cell Transplantation, University Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
1] Department of Stem Cell Transplantation, University Cancer Center Hamburg-Eppendorf, Hamburg, Germany [2] MLL Munich Leukemia Laboratory, Munich, Germany.
Bone Marrow Transplant. 2014 Jan;49(1):1-7. doi: 10.1038/bmt.2013.72. Epub 2013 May 27.
Despite overall improvements in outcomes of patients with diffuse large B cell lymphoma (DLBCL), ∼30-40% of patients develop relapsed or refractory disease. For patients with chemo refractory disease, or recurrent disease following autologous hematopoietic SCT (auto-HCT), the prognosis is poor, with no consensus on the optimal therapy. Currently, owing to the graft vs lymphoma effect, hematopoietic allogeneic hematopoietic cell transplantation (allo-HCT) is the only potentially curative option for such patients. In addition, many patients who are considered today for auto-HCT actually have a low likelihood of benefit. For example, a patient with prior rituximab exposure who relapses within 1 year of diagnosis and has a second-line age-adjusted International Prognosis Index of 2 or 3 at relapse has a <25% chance of being cured by auto-HCT. It is possible that such patients may be better served with an allo-HCT. Unfortunately, in many cases, allo-HCT applicability is limited by patient age, comorbidities, performance status and treatment-related toxicities. Recent attempts to improve the efficacy of auto-HCT, such as incorporating radio-immunotherapy into the conditioning regimen, have not resulted in improved outcomes. However, incorporation of novel agents such as anti-programmed death-1 antibodies as maintenance therapy after auto-HCT show promise. Allo-HCT in relapsed/refractory DLBCL patients can result in a 30-40% PFS rate at 3 years, in part due to a graft vs DLBCL effect. While reduced-intensity/non-myeloablative conditioning is increasingly being used, certain patients may benefit from myeloablative conditioning. We present an algorithm intended to discriminate which relapsed and refractory DLBCL patients are most likely to benefit from auto-HCT vs allo-HCT. New approaches, using novel agents that target the molecular heterogeneity in DLBCL, will be an essential component of moving the field forward. Lastly, we propose a prospective registry-based study as the only feasible mechanism to define the optimal position of allo-HCT in the overall treatment strategy for DLBCL. It is hoped that this review will promote the development of prospective multicenter efforts to determine whether such patients do, in fact, benefit from earlier and/or more effective implementation of allo-HCT.
尽管弥漫性大B细胞淋巴瘤（DLBCL）患者的总体预后有所改善，但仍有30%-40%的患者会出现复发或难治性疾病。对于化疗难治性疾病患者，或自体造血干细胞移植（auto-HCT）后复发的患者，预后较差，目前尚无关于最佳治疗方案的共识。目前，由于移植物抗淋巴瘤效应，异基因造血干细胞移植（allo-HCT）是这类患者唯一可能治愈的选择。此外，如今许多被考虑进行auto-HCT的患者实际上受益的可能性很低。例如，一名在诊断后1年内复发且复发时二线年龄校正国际预后指数为2或3的曾接受利妥昔单抗治疗的患者，通过auto-HCT治愈的机会小于25%。这类患者可能接受allo-HCT会更好。不幸的是，在许多情况下，allo-HCT的适用性受到患者年龄、合并症、体能状态和治疗相关毒性的限制。最近尝试提高auto-HCT疗效的方法，如将放射免疫疗法纳入预处理方案，但并未改善预后。然而，在auto-HCT后将抗程序性死亡-1抗体等新型药物作为维持治疗显示出前景。复发/难治性DLBCL患者进行allo-HCT，3年无进展生存率可达30%-40%，部分原因是移植物抗DLBCL效应。虽然越来越多地使用减低强度/非清髓性预处理，但某些患者可能从清髓性预处理中获益。我们提出一种算法，旨在区分哪些复发和难治性DLBCL患者最有可能从auto-HCT与allo-HCT中获益。使用针对DLBCL分子异质性的新型药物的新方法，将是推动该领域前进的重要组成部分。最后，我们提议开展一项基于前瞻性登记的研究，作为确定allo-HCT在DLBCL总体治疗策略中最佳位置的唯一可行机制。希望这篇综述将促进前瞻性多中心研究的开展，以确定这类患者是否真的能从更早和/或更有效地实施allo-HCT中获益。
