All-trans-retinoic acid-induced pseudotumor cerebri in acute promyelocytic leukemia

Abstract

All-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL). Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA) during the induction therapy in an adult with acute promyelocytic leukemia (APL).

Pseudotumor Cerebri in Acute Promyelocytic Leukemia Patients on Intergroup Protocol 0129: Clinical Description and Recommendations for New Diagnostic Criteria

“…Including the case presented, the authors identified 23 patients with PTC during ATRA treatment for APL, 11 of whom were adults 8–27,34,35 . Since that publication, an additional three case reports and one case series have been published 4,28,29,36 . Compiling all these patients and our four probable PTC patients (n= 35), the mean age at diagnosis of PTC was 23.5 years with a median age of 18 years, with a female to male ratio of 1.03:1 4,10,28,29,36 .…”

“…Since that publication, an additional three case reports and one case series have been published 4,28,29,36 . Compiling all these patients and our four probable PTC patients (n= 35), the mean age at diagnosis of PTC was 23.5 years with a median age of 18 years, with a female to male ratio of 1.03:1 4,10,28,29,36 . The mean age of diagnosis amongst these case reports may be an overestimate due to publication bias, as PTC is considered a more common complication in the pediatric population, as seen in our series.…”

“…The median time to the diagnosis of PTC after initiation of ATRA, when occurring during induction (n= 28), was 14.8 days (range 1–35 days). PTC also occurred during consolidation in two cases and maintenance in seven cases (occurring during both induction and maintenance for 2 patients and only during maintenance for 5 patients) 4,10,28,29,36 . Regarding treatment, ATRA was held in 30 of the 35 cases (86%) (in some cases after initial attempts to dose reduce), and in three additional cases after other therapeutic interventions failed 4,10,28,29,36 .…”

“…In a study comparing CSF retinol levels in patients with idiopathic PTC to those without, a higher level of vitamin A was noted in the CSF of affected patients, none of whom had known vitamin A toxicity 3 . Additionally, ATRA may alter the lipid constituents of the arachnoid villi which disturbs the normal transport system and therefore CSF cannot be absorbed 4 .…”

“…PTC has frequently been described in the literature as an adverse effect of ATRA therapy, usually in single case reports 4,7–29 , making an estimation of its true incidence difficult. Here, we discuss the series of patients on clinical trial I0129 in which there was a clinical suspicion for PTC, focusing on diagnostic criteria in this select population, and how to treat such patients.…”