title: Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation.
abstract: We investigated whether a T cell-reduced allogeneic stem cell transplant (SCT) with minimal conditioning and subsequent donor lymphocyte infusions (DLI) could reduce the incidence and severity of GVHD while retaining stable engraftment. Five patients with hematological malignancies (three MM, one CLL, one Chediak-Higashi syndrome) were conditioned with TBI (200 cGy). One patient additionally received fludarabine (120 mg/m(2)). CsA and mofetyl-mycophenolate (MMF) were administered to prevent GVHD. All patients were grafted with >3 x 10(6)/kg highly purified CD34(+) cells together with 2 x 10(6)/kg CD3(+) cells (three patients) or 1 x 10(5)/kg CD3(+) cells (two patients). Quick hematopoietic recovery and initial mixed donor chimerism was observed. Treatment-related toxicity was minimal in all but one patient who died of treatment-refractory GVHD on day 112. The four other patients only achieved partial donor T cell chimerism. BM and PBMC donor chimerism was lost between day 40 and 209 despite DLI. Three patients are alive with disease and one is in CR. We conclude that T cell-reduced SCT using 200 cGy as the conditioning regimen does not result in stable hematopoietic engraftment. Predominant donor T cell chimerism is not a prerequisite for initial allogeneic hematopoietic proliferation. However for sustained long-term engraftment it is of major importance.
authors.affiliation: III Medizinische Klinik, Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kreiter
authors.forename: N
authors.initials: N
authors.lastname: Winkelmann
authors.forename: P M
authors.initials: PM
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Schuler
authors.forename: T
authors.initials: T
authors.lastname: Fischer
authors.forename: A J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: H G
authors.initials: HG
authors.lastname: Derigs
authors.forename: K
authors.initials: K
authors.lastname: Kolbe
mesh_terms: D000328:Adult; D002609:Chediak-Higashi Syndrome / Q000628:therapy; D016572:Cyclosporine / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*; D017211:Treatment Failure; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine