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

摘要

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 (CsA₂₁) 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 CsA₂₁ 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 CsA₂₁. Extensive cGvHD incidence was 60.6% at 1 year. Reduction of MTX to 2–3 doses, but not MTX omission or CsA₂₁, was associated with greater incidence of cGvHD affecting ≥3 organs. Median IST duration was 22 months; neither MTX nor CsA₂₁ influenced this. IST duration was significantly greater in patients receiving a CD34 dose below median. Neither MTX nor CsA₂₁ altered survival or relapse outcomes. MTX influences GvHD following T-replete RIC sibling HSCT.