Hematology and Bone Marrow Transplant Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Piazza OMS, 1, 24127, Bergamo, Italy.
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genova, Italy.
BMC Cancer. 2020 Oct 2;20(1):956. doi: 10.1186/s12885-020-07461-5.
L-asparaginase (L-ASP) is a key component of acute lymphoblastic leukemia (ALL) treatment, but its use in clinical practice raises challenges to clinicians due to a relatively high incidence of drug-related adverse events, mainly in adult patients. In the past years the use of ASP in adult population has been mainly limited due to a poor knowledge of its safety profile and to an approximate management of ASP-related toxicity. Recently the development of pediatric-inspired treatment protocols for adult ALL has led to a wider use of ASP and since 2010 in Italy three national treatment protocols including Pegylated asparaginase (Peg-ASP) have been sequentially developed for adolescents, young adults and adults with Philadelphia-negative (Ph-) ALL.
With the aim to better understand the approach adopted in Italian centers for the management and prevention of Peg-ASP toxicity in adult ALL and to provide practical, consensus-based recommendations, a board of 6 Italian clinicians, with known expertise in adult ALL, designed 41 consensus statements on current challenges on the management of Peg-ASP associated toxicity. A group of 19 clinical experts in the field then rated these statements using the 5-point Likert-type scale (1 = strongly disagree; 5 = strongly agree).
The main Peg-ASP related issues identified by the board included: 1) clinician's attitudes; 2) toxicity profile; 3) hypersensitivity reactions; 4) hepatic toxicity; 5) hepatic and/or metabolic toxicity; 6) hemorrhagic/thrombotic toxicity; 7) pancreatitis; 8) metabolic toxicity management and prevention; 9) activity levels monitoring. Overall, participants agreed on most statements, except those addressing the potential contraindications to the treatment with Peg-ASP, such as patients with a diagnosis of chronic liver disease or the subsequent administrations of the drug in patients who had previously developed chemical pancreatitis or severe metabolic toxicity. Participants agreed that adult patients with ALL should receive Peg-Asp because this drug is essential to improve treatment results.
The panel agreed that a critical evaluation of specific risk factors for each patient is crucial in order to reduce the risk of adverse events and specific advices in the management of Peg-ASP toxicities are reported.
L-天冬酰胺酶（L-ASP）是急性淋巴细胞白血病（ALL）治疗的关键组成部分，但由于其在临床实践中相对较高的药物相关不良反应发生率，主要在成年患者中，给临床医生带来了挑战。在过去的几年中，由于对其安全性特征的了解不足以及对 ASP 相关毒性的近似管理，ASP 在成年人群中的使用主要受到限制。最近，为成人 ALL 制定了受儿科启发的治疗方案，这导致了 ASP 的更广泛使用，自 2010 年以来，意大利已经为青少年、年轻成人和费城阴性（Ph-）ALL 患者制定了三个包含聚乙二醇化天冬酰胺酶（Peg-ASP）的国家治疗方案。
为了更好地了解意大利中心在成人 ALL 中管理和预防 Peg-ASP 毒性的方法，并提供实用的、基于共识的建议，一个由 6 名在成人 ALL 方面具有专业知识的意大利临床医生组成的委员会设计了 41 个共识声明，内容涉及 Peg-ASP 相关毒性管理方面的当前挑战。然后，一组 19 名该领域的临床专家使用 5 分李克特量表（1=强烈不同意；5=强烈同意）对这些声明进行了评分。
委员会确定的主要 Peg-ASP 相关问题包括：1）临床医生的态度；2）毒性特征；3）过敏反应；4）肝毒性；5）肝和/或代谢毒性；6）出血/血栓形成毒性；7）胰腺炎；8）代谢毒性管理和预防；9）活动水平监测。总体而言，参与者对大多数声明表示同意，除了那些涉及 Peg-ASP 治疗潜在禁忌症的声明，例如患有慢性肝脏疾病的患者或之前发生过化学性胰腺炎或严重代谢毒性的患者随后使用该药物。参与者一致认为，ALL 成年患者应接受 Peg-Asp，因为这种药物对于改善治疗结果至关重要。
专家组一致认为，对每个患者的特定危险因素进行批判性评估对于降低不良事件的风险至关重要，并报告了 Peg-ASP 毒性管理方面的具体建议。
