title: Methotrexate dose delivery is more important than ciclosporin level in graft-versus-host disease prophylaxis following T-replete reduced-intensity sibling allogeneic stem cell transplant.
abstract: We investigated the contributions of methotrexate (MTX) and ciclosporin (CsA) prophylaxis to acute/chronic graft-versus-host disease (a/cGvHD) prevention following reduced-intensity conditioned allogeneic haematopoietic stem cell transplant (HSCT). Ninety-two fludarabine-melphalan sibling allo-SCT received CsA. Nine, 30 and 47 patients received no MTX, 2-3 doses and 4 doses, respectively. Cumulative CsA blood level to day 21 (CsA(21)) was calculated. Grades II-IV aGvHD incidence was 37.2%. In multivariate analysis, MTX omission and increasing donor age significantly associated with aGvHD incidence whilst MTX reduction and CsA(21) did not. Median duration of first immunosuppressive therapy (IST) for aGvHD was 68 days; duration of first IST was significantly longer in older patients but was not associated with MTX or CsA(21). Extensive cGvHD incidence was 60.6% at 1 year. Reduction of MTX to 2-3 doses, but not MTX omission or CsA(21), was associated with greater incidence of cGvHD affecting ≥3 organs. Median IST duration was 22 months; neither MTX nor CsA(21) influenced this. IST duration was significantly greater in patients receiving a CD34 dose below median. Neither MTX nor CsA(21) altered survival or relapse outcomes. MTX influences GvHD following T-replete RIC sibling HSCT.
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK. Patrick.Medd@orh.nhs.uk.
authors: Patrick
authors: P
authors: Medd
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Ian
authors: I
authors: Monk
authors: Nuffield Department of Clinical and Laboratory Sciences, University of Oxford, Oxford, UK.
authors: Robert
authors: R
authors: Danby
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Ram
authors: R
authors: Malladi
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Ruth
authors: R
authors: Clifford
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Amanda
authors: A
authors: Ellis
authors: NHS Blood and Transplant Oxford Centre, Oxford, UK.
authors: David
authors: D
authors: Roberts
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Chris
authors: C
authors: Hatton
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.|Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors: Paresh
authors: P
authors: Vyas
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Tim
authors: T
authors: Littlewood
authors: Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
authors: Andy
authors: A
authors: Peniket
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence; D035781:Siblings; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate