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Amsacrine combined with etoposide and methylprednisolone is a feasible and safe component in first-line intensified treatment of pediatric patients with high-risk acute lymphoblastic leukemia in CoALL-08-09 trial
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  • Gabi Escherich,
  • Kerstin Mezger,
  • Sabine Ebert,
  • Hannah Muhle,
  • Udo zur Stadt,
  • Arndt Borkhardt,
  • Dagmar Dilloo,
  • Jörg Faber,
  • Tobias Feuchtinger,
  • Thomas Imschweiler,
  • Norbert Jorch,
  • Arnulf Pekrun,
  • Irene Schmid,
  • Franziska Schramm,
  • Martin Zimmermann,
  • Martin Horstmann
Gabi Escherich
University hospital Hamburg

Corresponding Author:escherich@uke.de

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Kerstin Mezger
University hospital Hamburg
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Sabine Ebert
University hospital Hamburg
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Hannah Muhle
University hospital Hamburg
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Udo zur Stadt
University Medical Center Hamburg Eppendorf
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Arndt Borkhardt
Heinrich Heine University
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Dagmar Dilloo
University Hospital Bonn
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Jörg Faber
University Medical Center
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Tobias Feuchtinger
University Hospital Munich
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Thomas Imschweiler
6Department of Pediatric Hematology and Oncology, Helios Hospital
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Norbert Jorch
Gilead Children Hospital
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Arnulf Pekrun
Klinikum Bremen-Mitte gGmbH
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Irene Schmid
Children`s Hospital of the Ludwig-Maximilians-University, Munich
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Franziska Schramm
University Medical Center Hamburg Eppendorf
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Martin Zimmermann
Hannover Medical School
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Martin Horstmann
Research Institute Childrens Cancer Center Hamburg
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Abstract

Background The prognosis of children with acute lymphoblastic leukemia (ALL) has improved considerably over the past decades. However, to achieve cure in patients with refractory disease or relapse new treatment options are mandatory. Methods In the multicenter-trial CoALL-08-09, an additional treatment element consisting of the rarely used chemotherapeutic agent amsacrine combined with etoposide and methylprednisolone (AEP) (amsacrine 2 x 100 mg/m2, etoposide 2 x 500 mg/m2 and methylprednisolone 4 x 1000 mg/m2) was implemented into the first-line treatment of pediatric patients with a poor treatment response at the end of induction (EOI) measured by minimal residual disease (MRD). These patients were stratified into a high-risk intensified arm (HR-I) including an AEP element at the end of consolidation. Patients with induction failure (IF), i.e. lack of cytomorphological remission EOI, were eligible for hematopoietic stem cell transplantation (HSCT) after remission had been reached later on. These patients received AEP as a part of their MRD-guided bridging-to-transplant treatment. Results A significant improvement in probality of overall survival (pOS) for the CoALL-08-09 HR-I patients was noted compared to MRD-matched patients from the preceding CoALL-07-03 trial in the absence of severe or persistent treatment-related toxicities. Relapse rate and probability of event-free survival (pEFS) did not differ significantly between trials. In patients with IF a stable or improved MRD response after AEP was observed without severe or persistent treatment-related toxicities. Conclusion In conclusion, AEP is well-tolerated as a component of the HR treatment and useful in bridging-to-transplant settings.
27 May 2022Submission Checks Completed
27 May 2022Assigned to Editor
27 May 2022Submitted to Pediatric Blood & Cancer
28 May 2022Reviewer(s) Assigned
29 Jun 2022Review(s) Completed, Editorial Evaluation Pending
30 Jun 2022Editorial Decision: Revise Major
27 Jul 20221st Revision Received
27 Jul 2022Submission Checks Completed
27 Jul 2022Assigned to Editor
28 Jul 2022Reviewer(s) Assigned
11 Aug 2022Review(s) Completed, Editorial Evaluation Pending
12 Aug 2022Editorial Decision: Accept