title: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
abstract: Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
authors.affiliation: Royal Free and University College Medical School, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Pawson
authors.forename: M N
authors.initials: MN
authors.lastname: Potter
authors.forename: P
authors.initials: P
authors.lastname: Theocharous
authors.forename: M
authors.initials: M
authors.lastname: Lawler
authors.forename: M
authors.initials: M
authors.lastname: Garg
authors.forename: J A
authors.initials: JA
authors.lastname: Yin
authors.forename: K
authors.initials: K
authors.lastname: Rezvani
authors.forename: C
authors.initials: C
authors.lastname: Craddock
authors.forename: S
authors.initials: S
authors.lastname: Rassam
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
mesh_terms: D000208:Acute Disease; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D000069585:Filgrastim; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage*; D007938:Leukemia / Q000628:therapy*; D007951:Leukemia, Myeloid / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D011994:Recombinant Proteins; D012008:Recurrence; D012086:Reoperation; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; D000069585:Filgrastim; D015255:Idarubicin