Comparison of continuous versus intermittent infusion cyclosporine and impact on transplant related outcomes in allogeneic transplant recipients.

INTRODUCTION: Continuous infusion (CIVI) cyclosporine (CsA) is an alternative for allograft recipients intolerant of twice daily infusions (TDI). The importance of achieving therapeutic levels of CsA early after allogeneic HCT has been demonstrated in previous studies. Our study evaluated the incidence of acute graft versus host disease (GVHD) and survival among patients receiving CIVI vs. TDI CsA during their first allogeneic HCT. METHODS: A retrospective study of adult patients undergoing first allogeneic HCT at the University of Minnesota Medical Center between 2011 and 2017. Patients were grouped according to the administration method. The primary outcome was the occurrence of acute grade II-IV GVHD by day +180. Secondary outcomes included the 1-year incidence of chronic GVHD, relapse, and overall survival. RESULTS: 42 patients intolerant of TDI CsA received CsA via CIVI for >48 hours for a median of 9 days (range, 3-32 days). CsA concentrations were similar between groups. We found no difference between the rates of grade II-IV acute (45% vs 53%, p = 0.59) or chronic (17% vs 30%, p = 0.20) GVHD or overall survival (57% vs 67%, p = 0.10). Subgroup analysis of patients that received myeloablative conditioning or umbilical cord blood did not reveal significant differences in GVHD or overall survival. Cumulative incidence of relapse was higher among the continuous infusion group (39% vs. 23%, p < 0.01). CONCLUSION: Due to the finding of increased risk of relapse, cyclosporine should be administered as traditional twice daily infusion unless necessary. A prospective clinical trial is needed to confirm these results.

The challenges of treating aspergillus abdominal aneurysm after hematopoietic cell transplant: Rapid voriconazole metabolizer.

Mycotic aneurysms are a fatal manifestation of disseminated fungal infections in immunocompromised hosts. We present a patient with an Aspergillus mycotic aneurysm after hematopoietic cell transplant. Due to CYP2C19 rapid metabolizer phenotype (*1/*17), therapeutic levels of voriconazole were unobtainable. Successful therapy was achieved with posaconazole salvage therapy and early, aggressive surgery. This case demonstrates the consequences of voriconazole rapid metabolism and the potential impact of genetic variants.

Rifampin-sirolimus-voriconazole interaction in a hematopoietic cell transplant recipient.

Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3-12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16-18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug-drug interactions.

Clofarabine desensitization: A case report: Leukemia research reports.

We describe a relapsed AML patient who had two prior severe reactions to clofarabine involving rigors, emesis, tachycardia, hypotension, and acute kidney injury. Given previous prolonged remission achieved with clofarabine and cytarabine therapy years prior, rechallenge was undertaken upon discovery of AML relapse. We designed a desensitization protocol performed with the first dose of clofarabine, leading to successful administration of the entire clofarabine/cytarabine treatment course. From this case we show promise for clofarabine rechallenge after prior hypersensitivity reactions in patients with few treatment options for relapsed AML.