title: Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation.
abstract: To determine whether T cell engraftment and recovery of B cell immunity could be improved, we prospectively treated 15 children with severe combined immunodeficiency disease (SCID) with megadoses of haplocompatible CD34(+) cells and a fixed number of CD3(+) cells without previous myeloablative chemotherapy. Evidence of T cell engraftment was seen in 73% of patients (95% confidence interval [CI] = 48%-90%). Engraftment was more likely in patients with X-linked SCID and in those with evidence of maternal engraftment at the time of diagnosis. In patients with T cell engraftment, the median time to development of a CD4 count > 200 cells/mm(3) and a phytohemagglutinin response > 50% of control was 1.2 and 4.9 months, respectively. Clearance of preexisting infections occurred after a median of 2.8 months. B cell function developed in 33% of engrafted patients (95% CI = 14%-61%). The 1-year event-free survival (EFS) rate was 60% (95% CI = 36%-80%), and the overall survival (OS) rate was 87% (95% CI = 61%-98%), with a median follow-up of 39 months. The use of megadoses of CD34(+) cells with a fixed number of CD3(+) cells in nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with SCID is associated with excellent engraftment, T cell recovery, and OS; however, B cell function does not recover in most patients.
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of California San Francisco Children's Hospital, San Francisco, CA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipai, Taiwan.
authors.forename: Giun-Yi
authors.initials: GY
authors.lastname: Hung
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of California San Francisco Children's Hospital, San Francisco, CA.
authors.forename: Biljana
authors.initials: B
authors.lastname: Horn
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of California San Francisco Children's Hospital, San Francisco, CA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dunn
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of California San Francisco Children's Hospital, San Francisco, CA.
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Oon
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of California San Francisco Children's Hospital, San Francisco, CA. Electronic address: mcowan@peds.ucsf.edu.
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
mesh_terms: D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000502:physiology; D002648:Child; D005260:Female; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007107:Immune System / Q000502:physiology; D007700:Kinetics; D018655:Lymphocyte Count; D008297:Male; D012038:Regeneration; D012074:Remission Induction; D016511:Severe Combined Immunodeficiency / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000502:physiology; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D018952:Antigens, CD34