Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421

David Becton, Gary V. Dahl, Yaddanapudi Ravindranath, Myron N. Chang, Fred G. Behm, Susana C. Raimondi, David R. Head, Kimo C. Stine, Norman J. Lacayo, Branimir Ivan Sikic, Robert J. Arceci, Howard Weinstein

Research output: Contribution to journalArticlepeer-review

Abstract

Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-gp)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML.

Original languageEnglish (US)
Pages (from-to)1315-1324
Number of pages10
JournalBlood
Volume107
Issue number4
DOIs
StatePublished - Feb 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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