Vyas Chintan, Jain Sandeep, Kapoor Gauri, Mehta Anurag, Takkar Chugh Parul
a Department of Pediatric Hematology Oncology , Rajiv Gandhi Cancer Institute and Research Centre , New Delhi , India.
c Department of Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
Pediatr Hematol Oncol. 2018 Aug-Sep;35(5-6):331-340. doi: 10.1080/08880018.2018.1538277. Epub 2018 Nov 29.
Pegylated asparaginase (P-Asp) though integral to acute lymphoblastic leukemia (ALL) therapy is often not accessible to patients in developing countries. We share our clinical experience with generic P-Asp along with monitoring of asparaginase activity.
In this prospective observational study, patients ≤18 years of age with ALL were assigned to receive either generic P-Asp or native asparaginase (N-Asp) in a non-randomized manner. Treatment protocol was based on ALL BFM-95 backbone. The dose of P-Asp was 1500 IU/m by intravenous route during induction (Ia) and re-induction (IIa) phase of therapy.
N-Asp or P-Asp was administered to 52 and 54 of the 106 eligible patients respectively. Demographic and disease characteristics were comparable in both arms. The mean trough levels for N-Asp and P-Asp were 156.87 ± 22.35 IU/L and 216.03 ± 73.40 IU/L, respectively (p value <0.001) and all patients achieved therapeutic levels during Ia. Incidence of asparaginase-attributable toxicity was similar in the two arms in both phases of treatment, although hospitalization due to noninfectious causes was more common in P-Asp arm during Ia (13% versus 0%, p value, 0.01). Clinical hypersensitivity and silent inactivation were not observed during Ia while these occurred in 13% and 5% of patients in the N-Asp arm and P-Asp arms of IIa, respectively. The 2-year event free survival for P-Asp and N-Asp groups was 84% and 80.7%, respectively (p value 0.85).
Generic P-Asp was observed to be efficacious and well tolerated in our patients and adequate therapeutic levels were sustained for 2 weeks.
聚乙二醇化天冬酰胺酶（P-Asp）虽然是急性淋巴细胞白血病（ALL）治疗不可或缺的药物，但在发展中国家，患者往往无法获得。我们分享了使用通用型P-Asp的临床经验以及天冬酰胺酶活性监测情况。
在这项前瞻性观察研究中，年龄≤18岁的ALL患者以非随机方式被分配接受通用型P-Asp或天然天冬酰胺酶（N-Asp）治疗。治疗方案基于ALL BFM-95方案。在诱导（Ia）和再诱导（IIa）治疗阶段，P-Asp的剂量为1500 IU/m²，通过静脉途径给药。
106例符合条件的患者中，分别有52例和54例接受了N-Asp或P-Asp治疗。两组的人口统计学和疾病特征具有可比性。N-Asp和P-Asp的平均谷浓度分别为156.87±22.35 IU/L和216.03±73.40 IU/L（p值<0.001），所有患者在Ia期间均达到治疗水平。在两个治疗阶段，两组中天冬酰胺酶所致毒性的发生率相似，尽管在Ia期间，P-Asp组因非感染性原因住院更为常见（13%对0%，p值为0.01）。在Ia期间未观察到临床超敏反应和沉默失活，而在IIa期间，N-Asp组和P-Asp组分别有13%和5%的患者出现这些情况。P-Asp组和N-Asp组的2年无事件生存率分别为84%和80.7%（p值为0.85）。
在我们的患者中，通用型P-Asp被观察到有效且耐受性良好，并且维持了2周的足够治疗水平。
