In vitro activity of oxazaphosphorines in childhood acute leukemia: Preliminary report.

• Authors: Jan Styczyński , Mariusz Wysocki , Robert Dębski , Walentyna Balwierz , Roma Rokicka-Milewska , Michał Matysiak , Anna Balcerska , Jerzy Kowalczyk , Jacek Wachowiak , Danuta Sońta-Jakimczyk , Alicja Chybicka
• Languages of publication: EN

Abstracts

EN

Glufosfamide (β-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n= 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 μM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.

Keywords

EN

ALL; leukemia; sensitivity; glufosfamide; resistance

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2002
• Volume: 49
• Issue: 1
• Pages: 221-225

Dates

published

2002

received

2001-09-10

revised

2002-01-03

accepted

2002-02-21

Contributors

author

Jan Styczyński

• Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland

author

Mariusz Wysocki

• Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland

author

Robert Dębski

• Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland

author

Walentyna Balwierz

• Department of Pediatric Hematology, Collegium Medicum Jagiellonian University, Kraków, Poland

author

Roma Rokicka-Milewska

• Department of Pediatric Hematology and Oncology, Medical University, Warszawa, Poland

author

Michał Matysiak

• Department of Pediatric Pulmonology, Alergology and Hematology, Medical University, Warszawa, Poland

author

Anna Balcerska

• Department of Pediatric Hematology, Oncology and Endocrinology, Medical University, Gdańsk, Poland

author

Jerzy Kowalczyk

• Department of Pediatric Hematology and Oncology, Medical University, Lublin, Poland

author

Jacek Wachowiak

• Department of Pediatric Hematology and Oncology, Medical University, Poznań, Poland

author

Danuta Sońta-Jakimczyk

• Department of Pediatric Hematology and Chemotherapy, Silesian Medical University, , Zabrze, Poland

author

Alicja Chybicka

• Department of Pediatric Hematology and Oncology, Medical University, Wrocław, Poland

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