title: Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.
abstract: In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.
authors.affiliation: City of Hope National Medical Center, Duarte, CA 91010, USA. robertorodriguez@coh.org
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez
authors.forename: P
authors.initials: P
authors.lastname: Parker
authors.forename: A
authors.initials: A
authors.lastname: Nademanee
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: M R
authors.initials: MR
authors.lastname: O'Donnell
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: H C
authors.initials: HC
authors.lastname: Fung
authors.forename: A Y
authors.initials: AY
authors.lastname: Krishnan
authors.forename: L
authors.initials: L
authors.lastname: Popplewell
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: M
authors.initials: M
authors.lastname: Angelopoulou
authors.forename: Z
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.forename: P M
authors.initials: PM
authors.lastname: Falk
authors.forename: R
authors.initials: R
authors.lastname: Spielberger
authors.forename: N
authors.initials: N
authors.lastname: Kogut
authors.forename: F
authors.initials: F
authors.lastname: Sahebi
authors.forename: D
authors.initials: D
authors.lastname: Senitzer
authors.forename: M
authors.initials: M
authors.lastname: Slovak
authors.forename: J
authors.initials: J
authors.lastname: Schriber
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009894:Opportunistic Infections; D011292:Premedication / Q000379:methods*; D011446:Prospective Studies; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine; D008558:Melphalan