title: Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood.
abstract: We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.
authors.affiliation: Department of Hematology and Postgraduate School of Hematology Farreras-Valentí, Hospital Clinic, University of Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: C
authors.initials: C
authors.lastname: Rozman
authors.forename: C
authors.initials: C
authors.lastname: Martínez
authors.forename: P
authors.initials: P
authors.lastname: Marín
authors.forename: J
authors.initials: J
authors.lastname: Briones
authors.forename: M
authors.initials: M
authors.lastname: Rovira
authors.forename: P
authors.initials: P
authors.lastname: Féliz
authors.forename: M C
authors.initials: MC
authors.lastname: Viguria
authors.forename: A
authors.initials: A
authors.lastname: Merino
authors.forename: J
authors.initials: J
authors.lastname: Sierra
authors.forename: R
authors.initials: R
authors.lastname: Mazzara
authors.forename: E
authors.initials: E
authors.lastname: Carreras
authors.forename: E
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000293:Adolescent; D000328:Adult; D001781:Blood Component Removal / Q000379:methods*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous