title: Intensive graft-versus-host disease prophylaxis is required after unrelated-donor nonmyeloablative stem cell transplantation.
abstract: Nonmyeloablative stem cell transplantation (NST) harnesses the graft-versus-tumor effect while minimizing regimen-related toxicity, and can result in donor chimerism and remission. Acute graft-versus-host disease (GVHD) and infections are major complications after sibling NST. Toxicity of unrelated-donor (UD) NST and the most appropriate GVHD prophylaxis in this setting remain poorly defined. We describe 25 patients who received UD-NST conditioned with fludarabine and cyclophosphamide. The first six patients received cyclosporine (Cs) and mycophenolate mofetil (MMF) (n=5) or methotrexate (MTX) (n=1) as GVHD prophylaxis (group 1) and all developed grade III-IV acute GVHD. The next 19 patients received the same conditioning regimen with the addition of alemtuzumab, and all received Cs/MTX post-transplant. Engraftment and donor chimerism were achieved in all but one evaluable patient. In all, 15 patients died: five of six deaths in group 1 were attributable to acute GVHD, while deaths in group 2 were due to infection or progressive disease (P=0.05). The combination of Cs/MMF is inadequate GVHD prophylaxis for UD-NST. The use of Cs, MTX, and alemtuzumab eliminated severe acute GVHD; its impact on response merits further study.
authors.affiliation: Bone Marrow and Stem Cell Transplant Programs, University of Pennsylvania Cancer Center, Philadelphia, PA, USA. awokoff@mail.med.upen.edu
authors.forename: A W
authors.initials: AW
authors.lastname: Loren
authors.forename: S M
authors.initials: SM
authors.lastname: Luger
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: D E
authors.initials: DE
authors.lastname: Tsai
authors.forename: S
authors.initials: S
authors.lastname: Schuster
authors.forename: S D
authors.initials: SD
authors.lastname: Nasta
authors.forename: S C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: A
authors.initials: A
authors.lastname: Perl
authors.forename: G
authors.initials: G
authors.lastname: Orloff
authors.forename: J C
authors.initials: JC
authors.lastname: Oliver
authors.forename: J
authors.initials: J
authors.lastname: Green
authors.forename: S G
authors.initials: SG
authors.lastname: Emerson
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine