Impact of cyclosporine A concentration on acute graft-vs-host disease incidence after haploidentical hematopoietic cell transplantation

Eur J Haematol. 2019 Jul;103(1):10-17. doi: 10.1111/ejh.13233. Epub 2019 May 14.

Abstract

Objectives: This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide.

Methods: Sixty-one consecutives patients who underwent Haplo-HCT were analyzed.

Results: At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. Patients having a lowest CsA concentration (<301 ng/mL; the cutoff value used to segregate the patients between low and high CsA concentrations) in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (P = 0.02), severe grade III-IV aGvHD (P = 0.03), cGvHD (P = 0.02), and extensive cGvHD (P = 0.04). In multivariate analysis, a higher CsA concentration (≥301 ng/mL) during the first week following Haplo-HCT was the only parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (RR = 0.21; P = 0.049 and RR < 0.001; P < 0.0001, respectively). We find no correlation between CsA concentration and relapse, non-relapse mortality, progression-free survival, GvHD-free and progression-free survival, or overall survival.

Conclusions: CsA could be initiated early before Haplo-HCT with achievement of high CsA concentration to reduce the risk of aGvHD without any detrimental effect on relapse.

Keywords: acute graft-vs-host disease; cyclosporine A; haploidentical stem cell transplantation; post-transplant cyclophosphamide.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Cyclophosphamide / administration & dosage
  • Cyclosporine / administration & dosage*
  • Cyclosporine / pharmacokinetics
  • Drug Monitoring
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacokinetics
  • Incidence
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors
  • Time-to-Treatment
  • Transplantation Conditioning
  • Transplantation, Haploidentical
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Cyclophosphamide