title: Favourable outcome for patients with myeloid disorders treated with fludarabine-melphalan reduced-intensity conditioning and allogeneic bone marrow stem cell transplantation without the use of T-lymphocyte-depleting antibodies.
abstract: We report the use of reduced-intensity conditioning (RIC)-matched sibling allogeneic bone marrow stem cell transplantation as a method of establishing a graft-vs.-leukaemia (GvL) effect against myeloid disorders using a fludarabine-melphalan protocol without the use of T-lymphocyte-depleting antibodies. The 16 patients in this group had predominantly poor-risk acute myeloid leukaemia (AML) (n=10), AML/myelodysplasia (MDS) (n=2) and MDS (n=4). All but one patient achieved full haematopoietic engraftment. Thirteen of 16 patients are alive and in continued complete remission on completion of this study with a median follow-up of 426 d (range 83-1524). The actuarial 4 yr disease-free and overall survival is 79% for both. Only one patient relapsed following transplant, giving a relapse rate of 6% during the study period. The treatment-related mortality was 13% (n= 2). Overall, acute graft-vs.-host disease (GvHD) occurred in 53% (8/15), with acute GvHD grade II or above occurring in 47% (7/15). In the 13 evaluable patients, chronic GvHD occurred in 46% (6/13), with this being extensive in three patients. These results suggest that a GvL effect can be delivered against poor-risk myeloid disorders with a low non-relapse mortality using this fludarabine-melphalan RIC protocol.
authors.affiliation: Department of Haematology, John Radcliffe Hospital, Oxford, UK. ram.malladi@ndcls.ox.ac.uk
authors.forename: R K
authors.initials: RK
authors.lastname: Malladi
authors.forename: A J
authors.initials: AJ
authors.lastname: Peniket
authors.forename: A E
authors.initials: AE
authors.lastname: Norton
authors.forename: A J
authors.initials: AJ
authors.lastname: Campbell
authors.forename: G P
authors.initials: GP
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Samol
authors.forename: H
authors.initials: H
authors.lastname: Eagleton
authors.forename: E
authors.initials: E
authors.lastname: Miller
authors.forename: G
authors.initials: G
authors.lastname: Morgenstern
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Keen-Mcguire
authors.forename: M
authors.initials: M
authors.lastname: Barnardo
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D035781:Siblings; 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