Secondary Intracranial Hypertension During ATRA/ATO Therapy in High-Risk Acute Promyelocytic Leukemia: A Case Report and Practical Management Framework.
7 affiliations
- 1Department of Hematology, Oncology and Tumor Immunology, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- 2Department of Internal Medicine, Bundeswehr Hospital Berlin, 10115 Berlin, Germany.
- 3Department of Neurology with Experimental Neurology and Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- 4Institute of Neuroradiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- 5Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- 6Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
- 7Research Group Biology of Malignant Lymphomas, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.
Abstract
All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) is the standard of care for acute promyelocytic leukemia (APL), including high-risk disease. Secondary intracranial hypertension (SIH), historically termed pseudotumor cerebri (PTC), is a recognized but uncommon and potentially therapy-limiting complication of retinoid exposure, reported predominantly in pediatric and young-adult patients and most frequently during induction. We report a 31-year-old man with high-risk microgranular APL in whom SIH was diagnosed during the first ATRA/ATO consolidation cycle. The clinical course included progressive headache, ocular pain, pulsatile tinnitus, focusing difficulties, visual deterioration, and diplopia. Ophthalmological assessment demonstrated bilateral papilledema with marked peripapillary retinal nerve fiber layer thickening despite preserved central visual acuity. Magnetic resonance imaging showed bilateral optic nerve sheath distension, prominent optic nerve heads, mild pituitary flattening, and bilateral transverse sinus stenosis. Lumbar puncture demonstrated an opening pressure of 32 cm H₂O with otherwise unremarkable cerebrospinal fluid; removal of approximately 30 mL resulted in immediate symptomatic improvement. Management consisted of temporary ATRA interruption, therapeutic lumbar punctures, acetazolamide, and individualized ATRA rechallenge and dose titration. Repeated attempts at dose escalation reproduced symptoms, and ATRA was ultimately maintained at a maximally tolerated dose of 30 mg/m²/day while full-dose ATO was continued. Molecular remission was achieved after the first consolidation cycle and remains sustained at 18-month follow-up. This case highlights the importance of recognizing ATRA-associated SIH throughout the treatment course and illustrates a pragmatic strategy for preserving ATRA exposure when standard-dose treatment is limited by neurological toxicity. However, the oncological equivalence of reduced-dose ATRA cannot be inferred from a single case.
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BibTeX
@article{roeh2026secondary,
title = {{Secondary Intracranial Hypertension During ATRA/ATO Therapy in High-Risk Acute Promyelocytic Leukemia: A Case Report and Practical Management Framework.}},
author = {Luca Roeh and Nigel Schaeper and Sebastian Schröder and Jan Friedrich Scheitz and Dorothea Cornelia Voigt and Simon Schallenberg and Martin Janz and Philipp le Coutre and Sebastian Stintzing and Daniel Noerenberg},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = oct,
doi = {10.3390/curroncol33100611},
url = {https://europepmc.org/article/MED/42930178},
note = {CC BY},
}
RIS
TY - JOUR
TI - Secondary Intracranial Hypertension During ATRA/ATO Therapy in High-Risk Acute Promyelocytic Leukemia: A Case Report and Practical Management Framework.
AU - Luca Roeh
AU - Nigel Schaeper
AU - Sebastian Schröder
AU - Jan Friedrich Scheitz
AU - Dorothea Cornelia Voigt
AU - Simon Schallenberg
AU - Martin Janz
AU - Philipp le Coutre
AU - Sebastian Stintzing
AU - Daniel Noerenberg
PY - 2026
DA - 2026/10/10
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100611
UR - https://europepmc.org/article/MED/42930178
AB - All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) is the standard of care for acute promyelocytic leukemia (APL), including high-risk disease. Secondary intracranial hypertension (SIH), historically termed pseudotumor cerebri (PTC), is a recognized but uncommon and potentially therapy-limiting complication of retinoid exposure, reported predominantly in pediatric and young-adult patients and most frequently during induction. We report a 31-year-old man with high-risk microgranular APL in whom SIH was diagnosed during the first ATRA/ATO consolidation cycle. The clinical course included progressive headache, ocular pain, pulsatile tinnitus, focusing difficulties, visual deterioration, and diplopia. Ophthalmological assessment demonstrated bilateral papilledema with marked peripapillary retinal nerve fiber layer thickening despite preserved central visual acuity. Magnetic resonance imaging showed bilateral optic nerve sheath distension, prominent optic nerve heads, mild pituitary flattening, and bilateral transverse sinus stenosis. Lumbar puncture demonstrated an opening pressure of 32 cm H₂O with otherwise unremarkable cerebrospinal fluid; removal of approximately 30 mL resulted in immediate symptomatic improvement. Management consisted of temporary ATRA interruption, therapeutic lumbar punctures, acetazolamide, and individualized ATRA rechallenge and dose titration. Repeated attempts at dose escalation reproduced symptoms, and ATRA was ultimately maintained at a maximally tolerated dose of 30 mg/m²/day while full-dose ATO was continued. Molecular remission was achieved after the first consolidation cycle and remains sustained at 18-month follow-up. This case highlights the importance of recognizing ATRA-associated SIH throughout the treatment course and illustrates a pragmatic strategy for preserving ATRA exposure when standard-dose treatment is limited by neurological toxicity. However, the oncological equivalence of reduced-dose ATRA cannot be inferred from a single case.
SN - 1198-0052
SN - 1718-7729
ER -