title: Allogeneic transplantation after reduced conditioning in high risk patients is complicated by a high incidence of acute and chronic graft-versus-host disease.
abstract: Background and Objectives. We studied the toxicity and efficacy of reduced intensity conditioning followed by allogeneic stem cell transplantation in 50 patients over 50 years old or with relative contraindications against myeloablative regimens. Diagnoses were chronic myeloid leukemia (n=15), acute myeloid leukemia (n=9), myelodysplastic syndromes (n=9), lymphoma (n=11) and refractory solid tumors (n=6). Design and Methods. Donors were identical siblings (n=25), non-identical family members (n=6) and unrelated volunteers (n=19). Peripheral blood stem cells (n=36) or bone marrow (n=14) were transplanted. The conditioning regimen consisted of fludarabine 180 mg/m(2), busulphan 8 mg/kg and rabbit antithymocyte globulin 40 mg/kg (Fresenius). Graft-versus-host disease (GVHD) prophylaxis was carried out with cyclosporin A (CSA) alone (n=17) or in combination with methotrexate (n=18) or mycophenolate mofetil (n=15). Results. Neutrophil counts >0.5/nL and platelet counts > 20/nL were reached after 17 (range 0-66) and 19 days (range 0-111), respectively. Three graft failures occurred. Fever lasted for a median of 2 days (range 0-15). Six patients developed veno-occlusive disease of the liver. Acute GVHD grade II-IV occurred in 47% of the patients and chronic GVHD in 46%. The 1-year overall survival probability was 44% (95% CI: 30-58%). GVHD-related complications were a major cause of the probability of 1-year non-relapse mortality of 31% (95% CI: 16-46%). Interpretation and Conclusions. In conclusion, the regimen itself can be carried out safely in patients with relative contraindications against myeloablative conditioning. However, GVHD causes significant non-relapse mortality in high risk patients.
authors.affiliation: Kliniken für Innere Medizin m. S. Hämatologie und Onkologie, Charité, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Held
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Andreas
authors.initials: A
authors.lastname: Krusch
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Marc
authors.initials: M
authors.lastname: Dubiel
authors.forename: Oliver
authors.initials: O
authors.lastname: Rick
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Siegert
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D002908:Chronic Disease; D000075202:Contraindications; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D012306:Risk; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality / Q000592:standards; D014184:Transplantation, Homologous; D016896:Treatment Outcome