title: A fludarabine, thiotepa reduced toxicity conditioning regimen designed specifically for allogeneic second haematopoietic cell transplantation after failure of previous autologous or allogeneic transplantation.
abstract: We present a phase II study of fludarabine 5 x 30 mg/m(2), thiotepa 3 x 5 mg/kg as preparative regimen specifically for allogeneic second haematopoietic stem cell transplantation (HCT) after failure of previous HCT. Forty-nine patients (median age 52 years, range 27-68) received an allogeneic second HCT after failed autologous (n=29) or allogeneic (n=20) HCT. Diagnoses were AML (n=18), ALL (n=3), multiple myeloma (n=11), lymphoma (n=16) and CML (n=1). GVHD prophylaxis consisted of CYA and mainly low dose alemtuzumab (40 mg). The median follow-up for patients alive is 528 days (range 217-1344). In 43 of 49 (88%) evaluable patients response rates were CR=19, PR=14 and SD=10 at one month. At one year, the probability (95% confidence interval) of relapse is 55.1 (38.2-72)% and the nonrelapse mortality (NRM) is 29 (14.2-44.4)%. Estimated survival at one year is 42.6 (28.7-56.6)% and event free survival is 38.1 (24.4-51.8)%. Survival was significantly better for patients experiencing relapse beyond one year, than for patients relapsing within one year from first transplantation (51.2 (33.5-68.9)% vs 27 (7-48.5)%; P=0.013). We conclude that this regimen is feasible and well tolerated for allogeneic second HCT.
authors.affiliation: Department of Haematology and Oncology, Albert Ludwigs-University Medical Center Freiburg, Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Grüllich
authors.forename: H
authors.initials: H
authors.lastname: Bertz
authors.forename: A
authors.initials: A
authors.lastname: Spyridonidis
authors.forename: C I
authors.initials: CI
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Finke
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012008:Recurrence; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage*; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D017211:Treatment Failure; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D016572:Cyclosporine; D013852:Thiotepa; D014740:Vidarabine; C024352:fludarabine