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

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) prophyla...

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Bibliographic Details
Published in:The Annals of pharmacotherapy 2015-09, Vol.49 (9), p.986-994
Main Authors: García-Martín, Paloma, Alarcón-Payer, Carolina, López-Fernández, Elisa, Moratalla, Lucía, Romero, Antonio, Sainz, Juan, Ríos, Rafael, Jurado, Manuel
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1060-0280
1542-6270
DOI:10.1177/1060028015593369