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.
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.
Neudorf
Steven
S
American Family Life Assurance Company (AFLAC) Cancer Center, Emory University/Children's Healthcare, Atlanta, GA, USA. sneudorf@choc.org
Sanders
Jean
J
Kobrinsky
Nathan
N
Alonzo
Todd A
TA
Buxton
Allen B
AB
Gold
Stuart
S
Barnard
Dorothy R
DR
Wallace
Joetta D
JD
Kalousek
Dagmar
D
Lange
Beverly J
BJ
Woods
William G
WG
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods* / Q000401:mortality; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D006529:Hepatomegaly; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D002066:Busulfan; D008727:Methotrexate