Allogeneic bone marrow transplantation in first remission for children with ultra-high-risk features of acute lymphoblastic leukemia: A children's oncology group study report.
The prognosis for childhood acute lymphoblastic leukemia (ALL) has improved dramatically over the past quarter of a century. Despite improvements in the treatment of childhood ALL, relapse still occurs in 20%-30% of patients. Although many of these relapses occur in the "standard-risk" patients, approximately 10% of these patients present at diagnosis with clinical and biological features that identify them as having a very high risk of relapse. Children (2 months to 21 years) with > or =1 ultra-high-risk feature (UHRF) of ALL in first remission treated on a frontline Children's Cancer Group (CCG) ALL study with a matched family allogeneic donor were eligible for study entry onto CCG-1921 and an allogeneic bone marrow transplant (AlloBMT). Each patient received fractionated total body irradiation (1200 cGy) and cyclophosphamide (120 mg/kg) conditioning therapy followed by unmobilized BM from a matched family donor. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporin. Twenty-nine patients with a median age of 8.7 years with UHRF ALL in first complete remission (CR1) received an AlloBMT from a family member. The incidence of grade II-IV acute GVHD was 20.7% and the incidence of chronic GVHD was 3.7%. AlloBMT conditioning regimen was well tolerated and only 1 patient (3%) had treatment-related mortality. Ten patients (35%) died due to progressive disease. The 5-year event-free survival (EFS) for all patients was 58.6% and patients without cytogenetic abnormalities had a 5-year EFS of 77.8%. The 5-year EFS rates for infants and non-infants were 20.0% and 66.7% (log-rank test, P = .01), respectively. Patients with Philadelphia chromosome-positive ALL had a 5-year EFS of 66.7%. The children with UHRF of ALL may benefit from AlloBMT in CR1, especially patients with primary induction failure and Philadelphia chromosome-positive ALL. Randomized prospective cooperative group studies are required to establish the role of allogeneic hematopoietic stem cell transplantation versus intensive chemotherapy in children with UHRF ALL in CR1.
Satwani
Prakash
P
Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University, New York, New York 10032, USA.
Sather
Harland
H
Ozkaynak
Fevzi
F
Heerema
Nyla A
NA
Schultz
Kirk R
KR
Sanders
Jean
J
Kersey
John
J
Davenport
Virginia
V
Trigg
Michael
M
Cairo
Mitchell S
MS
D000293:Adolescent; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods*; D012720:Severity of Illness Index; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous