Use of PEG-asparaginase in newly diagnosed adults with standard-risk acute lymphoblastic leukemia compared with E. coli-asparaginase: a retrospective single-center study

Abstract

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, and the long-term survival varies with different ages. We performed a retrospective analysis of 122 newly diagnosed adults with standard-risk ALL treated with Escherichia coli asparaginase (E. coli-asparaginase, n = 50) and polyethylene glycol-conjugated asparaginase (PEG-asparaginase, n = 72). No treatment-related mortality (TRM) occurred in the E. coli-asparaginase group, and 3 TRM events occurred in the PEG-asparaginase group without relation to asparaginase. In addition, 22 (44.0%) and 48 (66.7%) patients achieved a complete response (CR) on day 14 in the E. coli-asparaginase and PEG-asparaginase groups, respectively (P = 0.032). No different 5-year event-free survival (EFS) or overall survival (OS) rate (P = 0.632 and 0.769) was observed. Multivariate analysis revealed later CR (P = 0.008) and older age (P = 0.049) as adverse prognostic factors for both EFS and OS. In addition, we specifically monitored the known adverse effects of asparaginase, and no asparaginase-related death was observed. Allergy occurred in 9 patients using E. coli-asparaginase, and no patient in the PEG-asparaginase group suffered from allergies (P < 0.001). The incidence of other asparaginase-related toxicities was similar. We conclude that PEG-asparaginase can be safely and effectively used as asparaginase in adults with newly diagnosed standard-risk ALL.

Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission induction for acute lymphoblastic leukemia (ALL)

“…Hepatotoxicity was The occurrence of liver toxicity during remission induction determines subsequent on-time delivery of chemotherapy. In fact, chemotherapy was discontinued or delayed in 7 patients in our study and this agrees with other reports [4,6]. However, it should be noted that most PEG-ASP toxic effects are manageable and reversible.…”

“…In contrast to above-mentioned studies, only single patients developed grade 3/4 PEG-ASP-related toxicities in an analysis reported by Douer et al; where hyperbilirubinemia and transaminitis were found in 8% and 12% of patients, respectively. Although decreased fibrinogen and antithrombin concentrations were not associated with bleeding events, cryoprecipitate was prophylactically administered [6]. This supports our findings that no bleeding events were observed in our patient population despite severe hyperfibrinogenemia and decreased AT level after PEG-ASP in some tested patients.…”

“…Severe pancreatitis and deep vein thrombosis (DVT) occurred in 6%, and 2% treated subjects, respectively. However, it is important that the incidence and severity of adverse events did not differ between PEG-ASP and E. coli-asparaginase treatments [6]. Hepatotoxicity was The occurrence of liver toxicity during remission induction determines subsequent on-time delivery of chemotherapy.…”

Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro

“… 3 Asparaginase is an important component of chemotherapeutic regimens for acute lymphoblastic leukemia (ALL). 4 , 5 In addition, asparaginase exhibits antitumor activity against NK cell tumors in vitro and in vivo. 6 , 7 In 2000, Yong et al 8 conducted the first effective clinical trial of asparaginase in refractory or relapsed ENKTL.…”

“… 6 , 7 In 2000, Yong et al 8 conducted the first effective clinical trial of asparaginase in refractory or relapsed ENKTL. Since then, various asparaginase-based regimens 4 , 5 have emerged as promising treatments for ENKTL. However, a number of patients are resistant to asparaginase, leading to treatment failure and poor prognosis.…”