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 CoALL08-09 trial.

Autor: Mezger K; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Ebert S; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Muhle HE; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Stadt UZ; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Borkhardt A; Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Duesseldorf, Duesseldorf, Germany., Dilloo D; Department of Pediatric Hematology/Oncology, University Hospital Bonn, Bonn, Germany., Faber J; Department of Pediatric Hematology/Oncology, University Hospital Mainz, Mainz, Germany., Feuchtinger T; Dr. von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany., Imschweiler T; Department of Pediatric Hematology and Oncology, Helios Hospital, Krefeld, Germany., Jorch N; Department of Pediatric Hematology and Oncology, Hospital Bielefeld, Bielefeld, Germany., Pekrun A; Department of Pediatric Hematology and Oncology, Hospital Bremen-Mitte, Bremen, Germany., Schmid I; Dr. von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany., Schramm F; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Zimmermann M; Department of Pediatric Haematology and Oncology, Medical School Hannover, Hannover, Germany., Horstmann MA; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany., Escherich G; Clinic of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2022 Dec; Vol. 69 (12), pp. e29997. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1002/pbc.29997
Abstrakt: Background: The prognosis of children with acute lymphoblastic leukemia (ALL) has improved considerably over the past five decades. However, to achieve cure in patients with refractory or relapsed disease, novel treatment options are necessary.
Methods: In the multicenter trial Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (CoALL)08-09, one additional treatment element consisting of the rarely used chemotherapeutic agent amsacrine combined with etoposide and methylprednisolone (AEP) (amsacrine 2 × 100 mg/m 2 , etoposide 2 × 500 mg/m 2 , and methylprednisolone 4 × 1000 mg/m 2 ) was incorporated into the first-line treatment of pediatric patients with poor treatment responses 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), that is, with lack of cytomorphological remission EOI, were eligible for hematopoietic stem cell transplantation (HSCT) after remission had been reached. These patients received AEP as a part of their MRD-guided bridging-to-transplant treatments.
Results: A significant improvement in probability of overall survival (pOS) was noted for the CoALL08-09 HR-I patients compared to MRD-matched patients from the preceding CoALL07-03 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, stable or improved MRD responses after AEP were observed without severe or persistent treatment-related toxicities.
Conclusion: In conclusion, AEP is well tolerated as a component of the HR treatment and is useful in bridging-to-transplant settings.
(© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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