title: 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.
abstract: 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.
authors.affiliation: Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University, New York, New York 10032, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: Harland
authors.initials: H
authors.lastname: Sather
authors.forename: Fevzi
authors.initials: F
authors.lastname: Ozkaynak
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
authors.forename: Jean
authors.initials: J
authors.lastname: Sanders
authors.forename: John
authors.initials: J
authors.lastname: Kersey
authors.forename: Virginia
authors.initials: V
authors.lastname: Davenport
authors.forename: Michael
authors.initials: M
authors.lastname: Trigg
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: 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