Lazzarotto Davide, Testi Anna Maria, Fanin Matteo, Mosna Federico, Chiaretti Sabina, Papayannidis Cristina, Curti Antonio, Piccini Matteo, Fracchiolla Nicola, Fumagalli Monica, Zappasodi Patrizia, Imbergamo Silvia, Minetto Paola, Guolo Fabio, Lussana Federico, Cerrano Marco, Forghieri Fabio, Leoncin Matteo, Olivi Matteo, Lunghi Monia, Trappolini Silvia, Mazzone Carla, Defina Marzia, Aprile Lara, Pasciolla Crescenza, Ciccone Maria, Mauro Endri, Mulè Antonino, Grimaldi Francesco, Cambò Benedetta, Santoro Lidia, Delia Mario, Mancini Valentina, Cignetti Alessandro, Fanin Renato, Bonifacio Massimiliano, Dargenio Michelina, Ferrara Felicetto, Pizzolo Giovanni, Foà Robin, Candoni Anna
Clinica Ematologica - Centro Trapianti e Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.
Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, "Sapienza" Università di Roma, Roma, Italy.
Ann Hematol. 2025 Aug 27. doi: 10.1007/s00277-025-06550-4.
The adoption of pediatric-inspired regimens for the treatment of Ph-negative acute lymphoblastic leukemia (ALL) in adults has improved prognosis. However, the feasibility of these intensive regimens in older patients is limited, due to the increased incidence of therapy-related side effects, including those related to asparaginase. In this sub-analysis carried out by the Campus ALL network, 90 ALL patients aged 55 or more (median age 59 years) homogeneously treated in real-life according to the GIMEMA LAL1913 program, were analyzed to evaluate the feasibility and tolerability of pegaspargase (PEG-ASP) treatment. Among the 90 patients analyzed, 86 (96%) received PEG-ASP at least in one of the first two courses (C1-C2) of chemotherapy and were evaluated for toxicity and outcome. In detail, 51 patients received PEG-ASP in both courses and 35 in either C1 or C2. The most common adverse event was hepatic toxicity (HT), with 38% of patients experiencing any grade of HT at C1 (HT grade ≥ 3, 19%) and 23% at C2 (HT grade ≥ 3, 9%). Additionally, HT at C1 was the primary reason for withholding PEG-ASP at C2. Coagulopathy was the second most frequent toxicity (any grade of toxicity in 26% of patients at C1 and in 20% at C2). No deaths directly related to PEG-ASP therapy were reported. The CR rate after C1 and C3 was 94% and 93%, respectively. MRD negativity rate was 40% and 68%, respectively. The OS and DFS probability at 3 years was 54% and 47%, respectively. PEG-ASP administration in older ALL patients is feasible, but HT is a concern, being the major cause of PEG-ASP interruption. Therefore, a dose adjustment, according to age and concomitant comorbidities, is advisable to balance PEG-ASP efficacy with its toxicity.
采用针对儿童的方案治疗成人Ph阴性急性淋巴细胞白血病（ALL）已改善了预后。然而，由于包括与门冬酰胺酶相关的副作用在内的治疗相关副作用发生率增加，这些强化方案在老年患者中的可行性有限。在Campus ALL网络进行的这项亚分析中，对90例年龄在55岁及以上（中位年龄59岁）、根据GIMEMA LAL1913方案在现实生活中接受同质化治疗的ALL患者进行分析，以评估聚乙二醇化门冬酰胺酶（PEG-ASP）治疗的可行性和耐受性。在分析的90例患者中，86例（96%）至少在前两个化疗疗程（C1-C2）中的一个疗程接受了PEG-ASP治疗，并对毒性和结局进行了评估。具体而言，51例患者在两个疗程中均接受了PEG-ASP治疗，35例在C1或C2中的一个疗程接受了治疗。最常见的不良事件是肝毒性（HT），38%的患者在C1时出现任何级别的HT（HT≥3级，19%），在C2时为23%（HT≥3级，9%）。此外，C1时的HT是C2时停用PEG-ASP的主要原因。凝血障碍是第二常见的毒性反应（C1时26%的患者出现任何级别的毒性反应，C2时为20%）。未报告与PEG-ASP治疗直接相关的死亡病例。C1和C3后的完全缓解（CR）率分别为94%和93%。微小残留病（MRD）阴性率分别为40%和68%。3年时的总生存期（OS）和无病生存期（DFS）概率分别为54%和47%。在老年ALL患者中给予PEG-ASP是可行的，但HT是一个问题，是PEG-ASP中断的主要原因。因此，建议根据年龄和合并症进行剂量调整，以平衡PEG-ASP的疗效及其毒性。
