A Rare Complication in a Patient with Acute Promyelocytic Leukemia; ATRA and Posaconazole Associated Hypercalcemia

Abstract

All-trans retinoic acid (ATRA), a derivative of vitamin A, has dramatically altered the treatment landscape for acute promyelocytic leukemia (APL). APL is characterized by the abnormal maturation of myeloid cells, which become arrested at the promyelocyte stage. ATRA effectively induces these cells to differentiate and undergo apoptosis. While generally well-tolerated, ATRA has been associated with rare adverse effects, including hypercalcemia. This case report underscores the importance of vigilant monitoring for ATRA-related side effects, especially when combined with medications which inhibit cytochrome P450 enzymes. Antifungal prophylaxis is common during leukemia treatment. Here, we present a rare instance of hypercalcemia in a pediatric patient attributed to the concurrent use of posaconazole and ATRA. A 15-year-old girl presented with widespread bruising, abnormal uterine bleeding, and pancytopenia. Subsequent investigations led to an APL diagnosis. Classified as standard-risk APL, she received chemotherapy according to the acute myelogenous leukemia-Berlin-Frankfurt-Münster 2004 protocol. After an ATRA course was started in the third month of maintenance treatment, she applied to the hospital with constitutional symptoms of weakness and fatigue on the third day of treatment. In the biochemical tests of the patient, serum Ca concentration was determined to be 16.5 mg/dL. Parathormone was 64.3 pg/mL and the 25-OH D vitamin level was 22 ng/mL and so were within the normal limits. Complete blood count was within the normal range. Although hypercalcemia is a side effect seen in the combined use of ATRA and azole antifungals, to the best of our knowledge, this is the first report in the literature that it was observed in the pediatric age group due to the simultaneous use of posaconazole and ATRA.

Keywords

• all-trans retinoic acid (atra)
• posaconazole
• hypercalcemia