Acute Promyelocytic Leukemia Patients Receiving ATRA with and without Voriconazole Prophylaxis: Effect on Incidence and Outcomes of Differentiation Syndrome

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.