受 GIMEMA LAL1913 临床试验启发的强化计划治疗的 421 名费城阴性急性淋巴细胞白血病成年患者的结果：一项 Campus ALL 研究。
Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.
发表日期：2024 Aug 15
作者：
Davide Lazzarotto, Marco Cerrano, Cristina Papayannidis, Sabina Chiaretti, Federico Mosna, Nicola Fracchiolla, Patrizia Zappasodi, Silvia Imbergamo, Maria Ilaria Del Principe, Monia Lunghi, Federico Lussana, Matteo Piccini, Monica Fumagalli, Michelina Dargenio, Prassede Salutari, Fabio Forghieri, Teresa Giulia Da Molin, Massimiliano Bonifacio, Matteo Olivi, Fabio Giglio, Silvia Trappolini, Matteo Leoncin, Antonino Mule, Mario Delia, Crescenza Pasciolla, Francesco Grimaldi, Benedetta Cambo, Lidia Santoro, Fabio Guolo, Paola Minetto, Marzia Defina, Patrizia Chiusolo, Matteo Fanin, Endri Mauro, Lara Aprile, Carla Mazzone, Fabio Trastulli, Maria Ciccone, Marco De Gobbi, Alessandro Cignetti, Eleonora De Bellis, Valentina Mancini, Alfonso Piciocchi, Marco Vignetti, Giovanni Marsili, Irene Della Starza, Renato Fanin, Mario Luppi, Felicetto Ferrara, Giovanni Pizzolo, Renato Bassan, Robin Foa, Anna Candoni
来源：
HAEMATOLOGICA
摘要：
在成人费城阴性急性淋巴细胞白血病 (Ph-ALL) 中引入儿科启发疗法显着改善了患者的预后。在 Campus ALL 网络中，我们分析了临床试验之外根据 GIMEMA LAL1913 方案治疗的成年 Ph-ALL 患者的结果，以将现实数据与研究结果进行比较。我们连续纳入了 421 名患者，中位年龄为 42 岁。第一个疗程化疗后的完全缓解 (CR) 率为 94%，第三个疗程后 72% 的患者实现可测量残留病灶 (MRD) 阴性。 3年总生存率（OS）和无病生存率（DFS）分别为67%和57%。在多变量分析中，MRD 阳性对 DFS 产生负面影响。在仅包括极高风险 (VHR) 和 MRD 阳性病例的时间依赖性分析中，移植 (HSCT) 患者的 DFS 显着优于非 HSCT 患者 (P=0.0017)。在诱导期间，25% 的患者观察到≥2 级培门冬酶相关肝毒性（GIMEMA LAL1913 试验中这一比例为 12%，P=0.0003）。在这个大型现实生活中的 Ph-ALL 队列中，我们证实了与 GIMEMA LAL1913 临床试验相比非常高的 CR 率以及可叠加的 OS 和 DFS：C1 后的 CR 率 94% vs 85%，P=0.0004； 3 年 OS 67% vs 67%，P=0.94； 3 年 DFS 为 57% vs 63%，P=0.17。 HSCT 证实了其在 VHR 和 MRD 阳性患者中的重要作用。在现实生活中，与培门冬酶相关的毒性发生率明显较高，这强调了在存在危险因素的情况下调整剂量以避免过度毒性的重要性。
The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.