Curran Emily, Luskin Marlise R, Alachkar Houda, Aldoss Ibrahim, Burke Patrick W, Cassaday Ryan D, Karol Seth E, Perissinotti Anthony J, Rank Cecilie Utke, Schmiegelow Kjeld, Webster Jonathan, Douer Dan
University of Cincinnati, Cincinnati, OH.
Dana-Farber Cancer Institute.
Haematologica. 2025 Mar 20. doi: 10.3324/haematol.2024.286744.
Asparaginase (ASNase)-based chemotherapy regimens significantly improve survival outcomes in children, adolescent and young adult (AYA), and even adults with acute lymphoblastic leukemia/lymphoma (ALL); however, the incidence and severity of ASNase-associated adverse events (AEs) in adults may differ significantly from those reported in children. Strategies to mitigate, monitor for, and manage toxicities that allow adult ALL patients to receive full ASNase courses are needed. A representative 12-member panel of experts who treat AYA and adult ALL patients, incorporate ASNase into their treatment regimens, and conduct related research was assembled to consider opportunities to optimize the use of pediatric-inspired ALL regimens in these adult patients. Following 2 systematic biomedical literature searches from April 2009 through April 2024, a modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. After 2 iterative Delphi method surveys, 23 statements met the standardized definition of consensus, whereas 19 statements did not. Five statements were merged to avoid redundancy. The clinical statements were grouped into 5 distinct categories: 1) hepatotoxicity; 2) hypersensitivity reactions; 3) thromboembolic and coagulopathy complications; 4) pancreatitis and metabolic complications; and 5) dosing. The intent of these statements is to provide health care providers with information that will help them mitigate, monitor for, and manage the most common and/or unique ASNase-induced AEs in adult ALL patients, allowing these patients to receive more or all the planned ASNase doses and thereby improve outcomes.
基于天冬酰胺酶(ASNase)的化疗方案显著改善了儿童、青少年和青年(AYA)甚至成人急性淋巴细胞白血病/淋巴瘤(ALL)患者的生存结局;然而,成人中ASNase相关不良事件(AE)的发生率和严重程度可能与儿童报告的情况有显著差异。需要采取策略来减轻、监测和管理毒性,使成人ALL患者能够接受完整疗程的ASNase治疗。为此组建了一个由12名专家组成的代表性小组,这些专家治疗AYA和成人ALL患者,将ASNase纳入其治疗方案并开展相关研究,以探讨在这些成年患者中优化使用源自儿科的ALL治疗方案的机会。在2009年4月至2024年4月进行了2次系统的生物医学文献检索后,采用改良的德尔菲法将专家意见提炼为符合共识标准化定义的临床陈述。经过2轮德尔菲法调查,23条陈述符合共识的标准化定义,而19条陈述不符合。合并了5条陈述以避免冗余。临床陈述分为5个不同类别:1)肝毒性;2)过敏反应;3)血栓栓塞和凝血病并发症;4)胰腺炎和代谢并发症;5)给药。这些陈述的目的是为医疗保健提供者提供信息,帮助他们减轻、监测和管理成人ALL患者中最常见和/或独特的ASNase诱导的AE,使这些患者能够接受更多或全部计划的ASNase剂量,从而改善结局。