Transplantation-Associated Thrombotic Microangiopathy in Patients Treated With Sirolimus and Cyclosporine as Salvage Therapy for Graft-Versus-Host Disease

Ann Pharmacother. 2015 Sep;49(9):986-94. doi: 10.1177/1060028015593369. Epub 2015 Jul 9.

Abstract

Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation. Because sirolimus (SIR) and calcineurin inhibitor-either cyclosporine (CsA) or tacrolimus-have become more common as graft-versus-host disease (GVHD) prophylaxis, we are witnessing a higher frequency of this complication.

Objective: To analyze the incidence, timing, and management of TA-TMA in patients who received the combination of CsA and SIR as therapy for uncontrolled GVHD in one single center.

Methods: This was a retrospective analysis from February 2002 to June 2014 of the combination of SIR and CsA as salvage therapy in 61 patients with treatment-refractory or relapsed acute GVHD (n = 24) or chronic GVHD (n = 37) in a tertiary hospital.

Results: A total of 61 patients received CsA and SIR as salvage therapy for acute (n = 16), late acute (n = 8), overlap syndrome (n = 22), or classic chronic (n = 15) GVHD. We identified 13 patients with TA-TMA (21.3%), and the status of GVHD was active in 11 of 13 patients. Only 1 patient showed high CsA levels, and 6 of 13 patients had very high concentrations of SIR in blood. We used an enzyme inducer in 6 patients, which proved effective in 3. Overall survival for TA-TMA patients was inferior compared to that for non TA-TMA patients at 12 months (42.9% vs 51.9%) and 24 months (34.3% vs 49.1%), although this difference was not significant.

Conclusion: Prompt identification and good management of TA-TMA, with better control of GVHD, may contribute to a decrease in patient mortality that would result from this complication.

Keywords: cyclosporine; hematology; immunosuppressants; prophylaxis; transplants.

Publication types

  • Observational Study

MeSH terms

  • Acute Disease
  • Adult
  • Calcineurin Inhibitors / therapeutic use*
  • Chronic Disease
  • Cyclosporine / therapeutic use*
  • Female
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Male
  • Recurrence
  • Retrospective Studies
  • Salvage Therapy*
  • Sirolimus / therapeutic use*
  • Thrombotic Microangiopathies / drug therapy*
  • Thrombotic Microangiopathies / etiology
  • Thrombotic Microangiopathies / mortality

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Sirolimus