Adequate asparaginase is important to prevent central nervous system and testicular relapse of pediatric Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukemia

Abstract

Asparaginase (Asp) is one of the most important drugs for treating acute lymphoblastic leukemia (ALL). However, off‐protocol Asp administration (OPAA) or hypersensitivity may disturb its pharmacokinetic profile. In this retrospective study, we sought to determine whether OPAA and hypersensitivity to Escherichia coli asparaginase (E coli Asp) impaired extramedullary relapse prevention in a pediatric ALL cohort treated according to SCMC‐ALL‐2005 protocol from 2005 to 2014 at the Shanghai Children's Medical Center (SCMC). In total, 676 patients were enrolled in this study, including 369 with OPAA and 60 exhibiting hypersensitivity to E coli Asp. At the end of the most recent follow‐up, 58 patients had extramedullary relapse. The 5‐year cumulative extramedullary relapse incidence in patients with OPAA was 11.01%, whereas that in patients without OPAA was 5.28% (P = .0036). Moreover, the 5‐year cumulative extramedullary relapse incidence in patients that exhibited hypersensitivity to E coli Asp was 16.48%, whereas that in patients without hypersensitivity was 7.59% (P = .0195). Concerning the relapse site, OPAA not only increased central nervous system (CNS) relapse but testicular relapse as well. Based on Fine and Gray multivariate analysis, OPAA and hypersensitivity to Asp were independent risk factors for extramedullary relapse. In conclusion, to prevent extramedullary relapse of ALL, adequate duration to administrate Asp was more important than the total dosage, and more attention should be paid to Asp inadequate due to hypersensitivity.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front‐line with paediatric‐inspired regimens: A retrospective multicentre Campus ALL study

“…While it is well established that systemic asparaginase lowers asparagine levels in the CNS, it is uncertain whether this provides any additional benefit to prevent CNS dissemination 43 . Recent paediatric studies have reported discordant results 44,45 . In our series, all patients received asparaginase: further analyses on the doses administered and interruptions are warranted.…”

“…43 Recent paediatric studies have reported discordant results. 44,45 In our series, all patients received asparaginase: further analyses on the doses administered and interruptions are warranted.…”

Superior Survival with Allogeneic Hematopoietic Stem Cell Transplantation versus Chemotherapy for High-Risk Adult Acute Lymphoblastic Leukemia in PDT-ALL-2016 Pediatric-Inspired Cohort

“…In present protocol, we speculated that adequate and effective treatment with pediatricinspired regimen could induce durable remission to avoid early relapse, and subsequently spare enough time to reconstitute the immune system to exert GVL effect. Furthermore, the importance of a su cient dose of asparaginase for better survival in AYA ALL has been widely accepted, with patients received more than 20 weeks of asparaginase showing better survival compared to those with a lower cumulative dose [37][38][39][40] . Based on these studies, we scheduled allo-HSCT after 4 blocks of consolidation therapy, ensuring patients receive a su cient dose of asparaginase and achieve a deeper remission.…”