A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL

Author:

Popov Alexander1ORCID,Henze Günter2,Roumiantseva Julia1,Bydanov Oleh1,Belevtsev Mikhail3,Verzhbitskaya Tatiana45,Movchan Liudmila3,Tsaur Grigory45ORCID,Lagoyko Svetlana1ORCID,Zharikova Liudmila1,Myakova Natalia1,Litvinov Dmitry1,Khlebnikova Olga4,Streneva Olga45,Stolyarova Elena3,Ponomareva Natalia6,Novichkova Galina1,Fechina Larisa45,Aleinikova Olga1,Karachunskiy Alexander1

Affiliation:

1. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia

2. Department of Pediatric Oncology Hematology, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany

3. Belarussian Research Center for Pediatric Oncology, Hematology and Immunology, 223053 Minsk, Belarus

4. Regional Children’s Hospital, Ekaterinburg 620149, Russia

5. Research Institute of Medical Cell Technologies, Ekaterinburg 620026, Russia

6. Republican Children’s Hospital, Moscow 594268, Russia

Abstract

This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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