title: Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors.
abstract: We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.
authors.affiliation: Department of Blood and Marrow Transplantation, the University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 448, Houston, TX 77030, USA. nueno@mdanderson.org
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Yee Chung
authors.initials: YC
authors.lastname: Cheng
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondón
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.forename: James L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Couriel
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: de Lima
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.forename: Issa F
authors.initials: IF
authors.lastname: Khouri
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Giralt
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D012074:Remission Induction; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan