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

Research output: Contribution to journalArticle

Authors

  • Patrick Medd
  • Ian Monk
  • Robert Danby
  • Ruth Clifford
  • Amanda Ellis
  • David Roberts
  • Chris Hatton
  • Paresh Vyas
  • Tim Littlewood
  • Andy Peniket

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)266-78
Number of pages13
JournalInternational journal of hematology
Volume94
Issue number3
Publication statusPublished - Sep 2011

Keywords

  • Young Adult, Cyclosporine, Transplantation Conditioning, Humans, Aged, Transplantation, Homologous, Immunosuppressive Agents, Recurrence, Cause of Death, Kaplan-Meier Estimate, Adult, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Methotrexate, Siblings, Middle Aged, Female, Male