title: High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation.
abstract: The best strategies for non-myeloablative stem cell transplants (NST) are not known. We hypothesized that a high stem cell dose and post-transplant donor lymphocyte infusions (DLI) in a T cell-depleted NST setting may result in stable engraftment without severe GvHD. We used conditioning with 200 mg/kg cyclophosphamide, and ATG, a high peripheral stem cell dose of >10 x 10(6) CD34(+) cells/kg, T cell-depleted to <1 x 10(5) CD3(+) cells/kg followed by incremental DLI. Ten patients, 53 (42-61) years of age with hematological malignancy (CML in 3, MDS in 2, myeloma in 3 and CLL in 2) were included. All patients achieved initial engraftment, at a median 13.5 (10-20) days. Three patients achieved complete chimerism, four achieved a complete hematologic remission. In seven patients the graft ultimately failed. Acute GvHD grade II was seen in three patients after DLI. At a median follow-up of 28 months (range 15-35), eight patients are alive, none died of treatment-related complications. NST with T cell depletion to prevent GVHD results in a high graft failure rate. High stem cell dose (> or =10 x 10(6) CD34(+)cells/kg) and post-transplant DLI will not compensate for the lack of T cells to ensure stable engraftment.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Basel University Hospital, Switzerland.
authors.forename: J R
authors.initials: JR
authors.lastname: Passweg
authors.forename: S
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: G
authors.initials: G
authors.lastname: Favre
authors.forename: D
authors.initials: D
authors.lastname: Heim
authors.forename: M
authors.initials: M
authors.lastname: Ebnoether
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D017252:CD3 Complex; D002452:Cell Count; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods / Q000401:mortality / Q000592:standards; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D017252:CD3 Complex; D003520:Cyclophosphamide