title: Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience.
abstract: A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.
authors.affiliation: Texas Transplant Institute, Southwest Texas Methodist Hospital, San Antonio, Texas 78229, USA. Donna.Wall@MHShealth.com
authors.forename: Donna A
authors.initials: DA
authors.lastname: Wall
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.forename: Naynesh R
authors.initials: NR
authors.lastname: Kamani
authors.forename: Joel A
authors.initials: JA
authors.lastname: Brochstein
authors.forename: Haydar
authors.initials: H
authors.lastname: Frangoul
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Goyal
authors.forename: John T
authors.initials: JT
authors.lastname: Horan
authors.forename: Daniel
authors.initials: D
authors.lastname: Pietryga
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D000961:Antilymphocyte Serum / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation
chemical_list: D000961:Antilymphocyte Serum; D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D002066:Busulfan; D008558:Melphalan