Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital

Craig A. Hurwitz, Robert Krance, Michael J. Schell, Victor M. Santana, Malcolm K. Brenner, Raul Ribeirio, W. Mark Roberts, Hazem Mahmoud, Judith Belt, William Crom, Patricia D. Shearer, Joseph Mirro

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We examined the feasibility of maintaining specific plasma concentrations of ara-C and VP-16 in children with AML. Sixty-one children were treated with 6 sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara-C)/VP-16, (2) ara-C/daunorubicin (Dauno) , (3) VP-16/amsacrine (m-AMSA), (4) VP-16/ 5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine children had de novo AML, and 2 had a previous myelodysplastic syndrome. The number of patients with each specific FAB subtype was: MO - 1; M1 - 7; M2 - 24; M3 - 7; M4 - 5; M5 - 11; and M7 - 6. Simultaneous continuous infusions of ara-C and VP-16 (cycle 1) given at individualized doses to achieve drug plasma concentrations of 1 μm and 30 μM, respectively, produced complete remission (CR) in 26 of 61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle 2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML. Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that intense treatment with ara-C and VP-16 at doses individualized to achieve target plasma concentrations is feasible although severely myelosuppressive. It results in an acceptable CR rate, but does not improve EFS. Four sequential St. Jude Children's Research Hospital (SJCRH) studies of increasingly intense therapy failed to produce a significant improvement in EFS. We therefore developed a new treatment for pediatric patients with AML. Our current therapy evalautes the activity of a highly active new agent, 2-chlorodeoxyadenosine (2-CDA), followed by conventional chemotherapy with Dauno, ara-C, and VP-16. Children in CR with a suitable HLA compatible sibling donor undergo allogeneic bone marrow transplant. Patients lacking an HLA compatible sibling donor receive an autologous BMT after attaining CR followed by interleukin 2 (IL-2) in an attempt to stimulate host antileukemic effector cells.

Original languageEnglish (US)
Pages (from-to)39-43
Number of pages5
JournalLeukemia
Volume6
Issue numberSUPPL. 2
StatePublished - 1992

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Current strategies for treatment of acute myeloid leukemia at St Jude Children's Research Hospital'. Together they form a unique fingerprint.

Cite this