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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3655-3661.
Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-08-2705.
Submitted August 7, 2003
Accepted December 10, 2003
Allogeneic bone marrow transplantation for children with acute myelocytic leukemia in first remission demonstrates a role for graft versus leukemia in the maintenance of disease-free survival
Steven Neudorf*, Jean Sanders, Nathan Kobrinsky, Todd A Alonzo, Allen B Buxton, Stuart Gold, Dorothy R Barnard, Joetta D Wallace, Dagmar Kalousek, Beverly J Lange, and William G Woods
Children's Hospital of Orange County, Orange, CA, USA
Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Roger Maris Cancer Center, Fargo, ND, USA
University of Southern California Keck School of Medicine, Los Angeles, CA, USA
University of North Carolina, Chapel Hill, NC, USA
Izaak W. Killam Hospital for Children, Halifax, Nova Scotia, Canada
Children's Hospital of Philadelphia, Philadelphia, PA, USA
AFLAC Cancer Center, Emory University/Children's Healthcare, Atlanta, GA, USA
* Corresponding author; email: sneudorf{at}choc.org.
In Children's Cancer Group (CCG) study 2891, patients with newly diagnosed AML were assigned randomly to standard or intensive-timing induction chemotherapy. Patients in CR1 and who had a HLA identical, related donor or a donor disparate at a single class I or II locus were non-randomly assigned to receive a bone marrow transplant (BMT) using oral busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). Methotrexate only was given for graft-versus-host disease (GVHD) prophylaxis. One hundred fifty patients were transplanted. Grades 3 or 4 acute GVHD occurred in 9% of patients. Patients < 10 yrs of age had a lower incidence of grades 3 or 4 GVHD (4.6%) compared to patients  10 (14.3%)(P = 0.044). Disease-free survival (DFS) at 6 years was 67% and 42% for recipients of intensive and standard-timing induction therapies, respectively. Multivariate analysis showed that receiving intensive-timing induction therapy (P = 0.027) and having no hepatomegaly at diagnosis (P = 0.009) were associated with favorable DFS, and grades 3 and 4 acute GVHD were associated with inferior DFS. Multivariate analysis showed that grades 1 or 2 GVHD (P = 0.008) and no hepatomegaly at diagnosis (P = 0.014) were associated with improved relapse-free survival (RFS). Our results show that children >10 yrs of age are at higher risk for developing severe GVHD acute GVHD is associated with favorable RFS.
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