title: CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies.
abstract: Although T cell depletion of allografts used in BMT has reduced GVHD, it has been associated with inferior engraftment and an increased risk of relapse. We have found that T cell depletion by counterflow centrifugal elutriation (CCE) also results in depletion of CD34+ stem cells. In order to determine if the discarded CD34+ cells would improve engraftment, we undertook a phase II trial of allogeneic BMT in which 110 patients (median age 43) with a variety of hematologic malignancies received CD34+ stem cell augmented, elutriated marrow grafts. The T cell-depleted grafts were tightly controlled and contained a mean of 4.3 x 10(7) mononuclear cells/kg, 3.3 x 10(6) CD34+ cells/kg, 1.5 x 10(5) CFU-GM/kg and 5.5 x 10(5) CD3+ T cells/kg. Median time to engraftment of granulocytes (>500/microl) was 16 days and of platelets (>50000/microl) was 25 days, comparable to that seen with unmanipulated marrow. No mixed hematopoietic chimerism was observed that was not associated with disease relapse. The four patients (3.6%) who failed to engraft were all at high risk because of prior donor transfusions or underlying marrow disorders. The incidence of GVHD was dependent on the duration of cyclosporin A (CsA) immunosuppression. In patients who received CsA for > or = 80 days, the incidence of clinically significant acute GVHD (>stage 1) and extensive, chronic GVHD was 5% and 11%, respectively. Peritransplant (< or = 100 day post-BMT) mortality for this group of patients was 15%. Event-free survival in selected subsets of patients compared favorably to previous studies in which patients received unmanipulated marrow allografts.
authors.affiliation: The Johns Hopkins Oncology Center, Baltimore, MD 21287, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: O'Donnell
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
authors.forename: G B
authors.initials: GB
authors.lastname: Vogelsang
authors.forename: A
authors.initials: A
authors.lastname: Seber
authors.forename: R F
authors.initials: RF
authors.lastname: Ambinder
authors.forename: I
authors.initials: I
authors.lastname: Flinn
authors.forename: C
authors.initials: C
authors.lastname: Miller
authors.forename: D C
authors.initials: DC
authors.lastname: Marcellus
authors.forename: C
authors.initials: C
authors.lastname: Griffin
authors.forename: R
authors.initials: R
authors.lastname: Abrams
authors.forename: H G
authors.initials: HG
authors.lastname: Braine
authors.forename: M
authors.initials: M
authors.lastname: Grever
authors.forename: A D
authors.initials: AD
authors.lastname: Hess
authors.forename: S
authors.initials: S
authors.lastname: Piantadosi
authors.forename: S J
authors.initials: SJ
authors.lastname: Noga
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D016572:Cyclosporine