Acute Promyelocytic Leukemia Patients Receiving ATRA with and without Voriconazole Prophylaxis: Effect on Incidence and Outcomes of Differentiation Syndrome
Jason N. Barreto
Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota, USA.
John C. Kuth
Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota, USA
Candy S. Peskey
Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota, USA.
Ross A. Dierkhising
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Naseema Gangat
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
Mrinal M. Patnaik *
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
*Author to whom correspondence should be addressed.
Abstract
Background: The combination of all trans-retinoic acid (ATRA) and voriconazole may lead to increased ATRA exposure resulting in a higher incidence of differentiation syndrome (DS).
Patients and Methods: This single center analysis evaluated the incidence and outcomes of ATRA-induced DS in 46 adult patients with acute promyelocytic leukemia (APL) undergoing induction chemotherapy.
Results: Thirty-one patients (69% by day 60) received a chemotherapy regimen including ATRA coinciding with voriconazole administration and 15 patients underwent treatment without voriconazole. The overall incidence of DS was 36% (n=16) by day 60, with patients receiving voriconazole showing a trend towards a higher incidence (HR 2.31, CI 0.78-6.847, p=0.1308). This trend persisted after adjusting for BMI (HR 1.96, CI 0.65-5.94, p=0.23); however, a small number of DS events precluded statistical significance.
Conclusion: A trend towards an increased incidence and severity of ATRA-mediated DS was seen in adult APL patients receiving voriconazole prophylaxis during induction chemotherapy. This important finding warrants validation in larger studies.
Keywords: Acute promyelocytic leukemia, all-trans retinoic acid (ATRA), voriconazole, differentiation syndrome.