A 33-year-old Caucasian man presented to an outside hospital 6 years ago with pancytopenia. Comorbid conditions consisted of human immunodeficiency virus infection diagnosed 19 years ago and treated with highly active antiretroviral therapy, and an 8-year history of chronic kidney disease secondary to focal segmental glomerulosclerosis and congenital solitary kidney. Bone marrow at presentation was notable for 75% involvement with abnormal promyelocytes. Fluorescence in-situ hybridization studies and reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed the t(15;17) translocation and presence of the promyelocytic leukemia (PML)-RARα fusion transcript respectively; a diagnosis of APL was made. Induction therapy consisted of daunorubicin 45mg/m2 daily on days 1 through to 3 with cytarabine 100mg/m2 daily on days 1 through to 7 concurrent with all-trans retinoic acid (ATRA) 40mg/m2 administered twice daily. Two cycles of consolidation daunorubicin 45mg/m2 daily on days 1 through to 3 were subsequently administered followed by 4 months of maintenance ATRA therapy; ATRA was discontinued prematurely due to near lethal pancreatitis in the setting of marked hypertriglyceridemia associated with the drug. He achieved and remained in remission, confirmed by repeated RT-PCR, for 3 years.
He presented subsequently to our hospital with neutropenic fever, pancytopenia, and low-grade disseminated intravascular coagulation. Bone marrow aspiration demonstrated relapsed APL with 80 to 90% cellularity and promyelocytes compromising 66% of the differential leukocyte count, as well as the t(15;17)(q22;q12) translocation and PML-RARα fusion transcript.
Given the patient’s history of severe pancreatitis related to ATRA, induction consisted of single agent arsenic trioxide 0.1mg/kg IV every other day while receiving hemodialysis (commenced 6 months prior to the diagnosis of his relapse) four times weekly. Complete blood counts, sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose prothrombin time, activated prothrombin time, and fibrinogen were monitored daily. The QTc duration was monitored daily via an electrocardiogram as well as pre- and post-dialysis on dialysis days for the first 2 weeks of induction. Given an observed stability of the QTc, electrocardiograms were then monitored weekly. Magnesium and potassium levels were maintained above 2.0mEq/L and 4.0mmol/L respectively. Aspartate aminotransferase and alanine aminotransferase levels were monitored weekly. Following 60 days of induction, a persistently elevated PML-RARα fusion transcript was detected on RT-PCR. The dose of arsenic trioxide was then increased to 0.15mg/kg every other day and continued for an additional 60 days. During this interval the patient required a brief hospital stay and arsenic trioxide dose interruption for hyperglycemia, which was determined to be adult-onset insulin-dependent diabetes probably exacerbated by arsenic trioxide therapy. A bone marrow biopsy after the second 60-day period confirmed remission. Consolidation consisted of single agent idarubicin at 12mg/m2 on days 1 and 2 every 28 days for two cycles. Maintenance consisted of 27 doses of arsenic trioxide. Treatment commenced with 0.1mg/kg arsenic trioxide Monday, Wednesday, and Friday; excessive fatigue after nine doses prompted the remaining doses to be delivered on a Tuesday and Friday schedule.
The patient has moved from the area but remains alive and free of relapse at the time of this writing. Given his comorbidities, the patient was not felt to be a candidate for high-dose chemotherapy with stem cell support.