title: Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.
abstract: Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.
authors.affiliation: Department of Haematology, University Hospital Aintree, Liverpool, UK. ranjit.dasgupta@aintree.nhs.uk
authors.forename: R K
authors.initials: RK
authors.lastname: Dasgupta
authors.forename: S
authors.initials: S
authors.lastname: Rule
authors.forename: P
authors.initials: P
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: A
authors.initials: A
authors.lastname: Burnett
authors.forename: C
authors.initials: C
authors.lastname: Poynton
authors.forename: K
authors.initials: K
authors.lastname: Wilson
authors.forename: G M
authors.initials: GM
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.forename: C
authors.initials: C
authors.lastname: Richardson
authors.forename: E
authors.initials: E
authors.lastname: Wareham
authors.forename: A C
authors.initials: AC
authors.lastname: Stars
authors.forename: S M
authors.initials: SM
authors.lastname: Tollerfield
authors.forename: G J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D008558:Melphalan