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

Blood. 2004 May 15;103(10):3655-61. doi: 10.1182/blood-2003-08-2705. Epub 2004 Jan 29.

Abstract

In Children's Cancer Group (CCG) study 2891, patients who were recently diagnosed with acute myelocytic leukemia (AML) were assigned randomly to standard- or intensive-timing induction chemotherapy. Patients in first complete remission (CR1) and who had a human leukocyte antigen (HLA)-identical, related donor or a donor disparate at a single class I or II locus were nonrandomly assigned to receive a bone marrow transplant (BMT) by 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 received transplants. Grade 3 or 4 acute GVHD occurred in 9% of patients. Patients younger than 10 years had a lower incidence of grade 3 or 4 GVHD (4.6%) compared with patients 10 years or older (17.4%) (P =.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 =.027) and having no hepatomegaly at diagnosis (P =.009) was 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 =.008) and no hepatomegaly at diagnosis (P =.014) were associated with improved relapse-free survival (RFS). Our results show that children older than 10 years are at higher risk for developing severe GVHD; acute GVHD is associated with favorable RFS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antineoplastic Agents / administration & dosage*
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / methods*
  • Bone Marrow Transplantation / mortality
  • Busulfan / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / prevention & control
  • Graft vs Leukemia Effect*
  • Hepatomegaly
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Methotrexate / administration & dosage
  • Remission Induction / methods
  • Risk Factors
  • Survival Analysis
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents
  • Cyclophosphamide
  • Busulfan
  • Methotrexate