title: Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.
abstract: We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.
authors.affiliation: Bone Marrow Transplant Programs, University of Navarra, Pamplona, Spain. ynieto@unav.es
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.forename: Nigel
authors.initials: N
authors.lastname: Patton
authors.forename: Timothy
authors.initials: T
authors.lastname: Hawkins
authors.forename: Ruth
authors.initials: R
authors.lastname: Spearing
authors.forename: Scott I
authors.initials: SI
authors.lastname: Bearman
authors.forename: Roy B
authors.initials: RB
authors.lastname: Jones
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Rachel
authors.initials: R
authors.lastname: Rabinovitch
authors.forename: Chan
authors.initials: C
authors.lastname: Zeng
authors.forename: Anna
authors.initials: A
authors.lastname: Barón
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000401:mortality; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011446:Prospective Studies; D035781:Siblings; D033581:Stem Cell Transplantation / Q000401:mortality; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D019172:Transplantation Conditioning / Q000401:mortality; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine; D016559:Tacrolimus