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Advances in the pathophysiology and treatment of relapsed/refractory Hodgkin’s lymphoma with an emphasis on targeted therapies and transplantation strategies

机译:复发/难治性霍奇金淋巴瘤的病理生理学和治疗进展,重点是靶向治疗和移植策略

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Hodgkin’s lymphoma (HL) is highly curable with first-line therapy. However, a minority of patients present with refractory disease or experience relapse after completion of frontline treatment. These patients are treated with salvage chemotherapy followed by autologous stem cell transplantation (ASCT), which remains the standard of care with curative potential for refractory or relapsed HL. Nevertheless, a significant percentage of such patients will progress after ASCT, and allogeneic hematopoietic stem cell transplantation remains the only curative approach in that setting. Recent advances in the pathophysiology of refractory or relapsed HL have provided the rationale for the development of novel targeted therapies with potent anti-HL activity and favorable toxicity profile, in contrast to cytotoxic chemotherapy. Brentuximab vedotin and programmed cell death-1-based immunotherapy have proven efficacy in the management of refractory or relapsed HL, whereas several other agents have shown promise in early clinical trials. Several of these agents are being incorporated with transplantation strategies in order to improve the outcomes of refractory or relapsed HL. In this review we summarize the current knowledge regarding the mechanisms responsible for the development of refractory/relapsed HL and the outcomes with current treatment strategies, with an emphasis on targeted therapies and hematopoietic stem cell transplantation.
机译:一线疗法可高度治愈霍奇金淋巴瘤(HL)。然而,一线治疗完成后,少数患者出现难治性疾病或复发。这些患者接受挽救性化疗,然后进行自体干细胞移植(ASCT),这仍然是治疗标准,具有治疗顽固性或复发性HL的潜力。然而,这类患者中有很大一部分将在ASCT后进展,同种异体造血干细胞移植仍是该情况下唯一的治疗方法。与细胞毒性化学疗法相比,难治性或复发性HL的病理生理学的最新进展为开发具有有效的抗HL活性和有利的毒性特征的新型靶向疗法提供了理论依据。已证明,Brentuximab vedotin和基于程序性细胞死亡1的免疫疗法可有效治疗难治性或复发性HL,而其他几种药物在早期临床试验中也显示出了希望。为了改善难治性或复发性HL的疗效,这些药物中的几种已与移植策略结合使用。在这篇综述中,我们总结了有关难治性/复发性HL发生机制的最新知识以及当前治疗策略的结果,重点是靶向治疗和造血干细胞移植。

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