title: Graft manipulation and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation from mismatched unrelated and mismatched/haploidentical related donors in pediatric leukemia patients.
abstract: Transplant-related problems have been partially overcome by using reduced-intensity conditioning (RIC), graft engineering, and alternative donors. In all, 21 leukemia patients with no suitable donor received a hematopoietic stem cell transplantation from a mismatched/haploidentical related (n=16) or unrelated donor (n=5). Fludarabine-RIC and PBSC graft were used. Manipulation was done by CD34+ selection (n=9) or CD3/CD19 depletion (n=12). Results were compared with patients (n=26) conditioned with the same regimen and grafted with a CD34+-selected PBSC from identical related donors. Median time to neutrophil recovery was 12 days (range, 10-19 d). Platelet engraftment was faster with a CD3/CD19-depleted graft (median, 11 d; range, 9-21) than with a CD34+ graft (median, 14 d; range, 9-53; P=0.003). Full donor chimerism in bone marrow CD34+ cells was higher in CD3/CD19-depleted graft group compared with CD34+-selected group (P=0.02). CD3/CD19 depletion showed higher natural killer cell counts even after 1 year. Nonrelapse mortality (7% for matched CD34+-selected grafts and 11% for mismatched/haplo-CD3/CD19-depleted grafts), relapse probability (27% for related CD34+-selected patients and 33% for related CD3/CD19-depleted patients), and disease-free survival were similar for both the groups. In conclusion, using graft engineering procedures after RIC for hematopoietic stem cell transplantation offers a high probability of engraftment, fast immune recovery, and very low mortality even with mismatched donors.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation and Cell Therapy Unit, Niño Jesus Children Hospital, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez-Vicent
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez
authors.forename: Lorea
authors.initials: L
authors.lastname: Abad
authors.forename: Julian
authors.initials: J
authors.lastname: Sevilla
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramirez
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Diaz
mesh_terms: D000293:Adolescent; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D018655:Lymphocyte Count; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D011446:Prospective Studies; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents; D017252:CD3 Complex; D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine