title: Allogeneic hematopoietic cell transplantation in children with relapsed acute lymphoblastic leukemia isolated to the central nervous system.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is the standard of care for pediatric patients with early medullary relapse of acute lymphoblastic leukemia (ALL). Most patients with isolated central nervous system (CNS) relapse have good outcomes when treated with intrathecal and systemic chemotherapy followed by irradiation to the neuroaxis. However, the role of HCT remains unclear for those patients with early isolated CNS relapse (<18 months) or who had high risk disease at diagnosis. We therefore compared the HCT outcomes of 116 children treated at the University of Minnesota from 1991 to 2006 with relapsed ALL involving the CNS alone (CNS, n = 14), the bone marrow alone (BM, n = 85), or both bone marrow and CNS (BM + CNS, n = 17). There were no significant differences among groups in age at diagnosis or transplant, length of first complete remission (CR1), remission status (CR2 versus >or=CR3), graft source, or preparative regimen. The incidence of acute GVHD was similar between groups. Patients with isolated CNS relapse had the lowest cumulative incidence of mortality following transplant (CNS: 0%, BM: 19%, BM + CNS: 29%, P = .03) and relapse (CNS: 0% BM: 30%, BM + CNS: 12%, at 2 years, P = .01) and highest leukemia-free survival (CNS: 91%, BM: 35%, BM + CNS: 46%, P < .01) at 5 years. Risk factors for poor survival were: T cell leukemia or BCR-ABL gene rearrangement, history of marrow relapse, and receipt of HLA-mismatched marrow. These data support the use of allogeneic HCT in the treatment of children with poor prognosis isolated CNS relapse.
authors.affiliation: Pediatric Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Harker-Murray
authors.forename: Avis J
authors.initials: AJ
authors.lastname: Thomas
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.forename: Xianghua
authors.initials: X
authors.lastname: Luo
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Dusenbery
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000706:statistics & numerical data; D002490:Central Nervous System / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation / Q000706:statistics & numerical data; D016371:Cranial Irradiation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D017254:Leukemic Infiltration / Q000532:radiotherapy / Q000601:surgery*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome