Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.
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PMID:Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial. 1913 48

Acute graft-versus-host disease (aGVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Due to the poor prognosis for patients not responding to first-line steroids treatment, improvements in aGVHD therapy are needed. Everolimus is a promising candidate that combines immunosuppressive properties with anti-neoplastic effects. Here, we retrospectively reviewed the efficacy of everolimus with steroids as primary treatment in 13 patients with grade II to grade IV aGVHD after HSCT. Among them, 12 (92.3%) had complete response to everolimus with steroids without additional immunosuppressive agents. The median duration of therapy was 76 days (range 20-110). Asymptomatic hypertriglyceridemia was the most common therapy complication (69.2%), but treatment interruption was not needed. Thrombotic microangiopathy was rare (7.7%), but can be quickly solved by stopping everolimus and cyclosporine treatment. Other toxicities were manageable. Two patients developed chronic GVHD (15.4%), limited in one and extensive in the other. The overall survival was 76.9% with a median follow-up of 3.4 years after HSCT (range 0.7-5.7). Accordingly, everolimus with steroids were feasible for patients with aGVHD after HSCT as primary treatment. Further large-scale studies are required.
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PMID:Everolimus for pediatric patients with acute graft-versus-host disease after hematopoietic stem cell transplantation: A pilot study. 2909 97