title: Unrelated donor or partially matched related donor peripheral stem cell transplant with CD34+ selection and CD3+ addback for pediatric patients with leukemias.
abstract: Unmodified peripheral stem cell transplants are associated with an increased risk of extensive chronic GVHD. T depletion may reduce this risk, but the risk of graft failure or relapse may increase. To decrease the risks of both extensive chronic GVHD and graft failure, we added back a defined dose of CD3+ cells to CD34+ selected PSCs. Twenty-four patients were evaluable for outcome analysis. Donors were unrelated (23) or related (1). Conditioning was thiotepa, cyclophosphamide, and total body irradiation. Cyclosporine was used post transplant. Following CD34+ selection, a total of 5 x 10(5)/kg CD3+ cells were infused. Donors were matched for 12 patients. The median CD34+ dose infused was 7.1 x 10(6)/kg. Engraftment occurred in all patients at a median of 14 days (10-19). Twelve patients are alive in remission 15-34 months (median, 25) post PSCT. GVHD occurred in 17 patients, but was >grade II in only 2. Chronic GVHD occurred in 61.5% of evaluable patients, but was limited to skin and perioral cavity. Two patients relapsed, and 10 patients died of non-relapse causes. This study demonstrates that PSCT with CD34+ selection and a defined dose of CD3+ results in prompt engraftment and may limit development of extensive chronic GVHD.
authors.affiliation: Dept Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. bunin@email.chop.edu
authors.forename: N
authors.initials: N
authors.lastname: Bunin
authors.forename: R
authors.initials: R
authors.lastname: Aplenc
authors.forename: S
authors.initials: S
authors.lastname: Grupp
authors.forename: G
authors.initials: G
authors.lastname: Pierson
authors.forename: D
authors.initials: D
authors.lastname: Monos
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D017252:CD3 Complex; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D046148:Donor Selection / Q000379:methods; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000379:methods / Q000401:mortality; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D012074:Remission Induction / Q000379:methods; D013852:Thiotepa / Q000008:administration & dosage; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods / Q000401:mortality
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D003520:Cyclophosphamide; D013852:Thiotepa