Original Manuscript
Leukemia (2005) 19, 2054–2062. doi:10.1038/sj.leu.2403925; published online 1 September 2005
Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891
F O Smith1, T A Alonzo2,3, R B Gerbing3, W G Woods4 and R J Arceci5 for the Children's Cancer Group
- 1Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA
- 2Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
- 3Children's Oncology Group, Arcadia, CA, USA
- 4Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA
- 5The Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, MD, USA
Correspondence: Dr FO Smith, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. Fax: +1 513 636 3549; E-mail: frank.smith@cchmc.org
Received 31 January 2005; Accepted 10 June 2005; Published online 1 September 2005.
Abstract
The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77–78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65
9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.
Keywords:
pediatrics, acute myeloid leukemia, bone marrow transplantation
