We investigated whether thiamine deficiency was common in myeloproliferative neoplasms (MPN) and associated with different therapies. We measured thiamine levels in 92 MPN patients and correlated the results with disease subtypes and treatments. The median thiamine level was within normal range and showed no correlation with MPN subtype or treatment, including ruxolitinib. Thiamine deficiency does not appear to be a common problem in UK MPN patients. This suggests that thiamine deficiency leading to Wernicke's encephalopathy seen in patients treated with fedratinib was likely directly related to that drug.
1. Natalia Curto Garcia1, Claire N Harrison2, Donal P McLornan2, Deepti H Radia2. 1Royal Free London NHS Foundation Trust, Royal Free Hospital,
London, United Kingdom. 2Guy´s and St. Thomas NHS Foundation Trust, London, United Kingdom.
OBJECTIVES
METHODS
We sought to investigate whether thiamine deficiency was common in myeloproliferative neoplasms (MPN) and whether there was
any association between different therapies including other JAK inhibitors and thiamine levels.
We determined thiamine levels in 92 MPN patients and correlated results with disease subtypes and treatments for MPN.
• Ogershok, P. R et al. (2002) Wernicke Encephalopathy in Nonalcoholic Patients. The American
Journal of the Medical Sciences, 323, 107-111.
• Sechi G. & Serra A. (2007) Wernicke's encephalopathy: new clinical settings and recent advances in
diagnosis and management. Lancet Neurology, 6, 442-55.
•Talpaz, M., et al. (2012) A phase II randomized dose ranging study of the JAK2-selective inhibitor
SAR302503 in patients with intermediate-2 or high-risk primary myelofibrosis (MF), post-polycythemia
vera (PV) MF, or post-essential thrombocythemia (ET) M F. Blood (ASH Annual Meeting Abstracts),
120, Abstract 2837.
• Pardanani, A., et al. (2015) Safety and Efficacy of Fedratinib in Patients With Primary or Secondary
Myelofibrosis: A Randomized Clinical trial. JAMA Oncology, 1, 643-651.
doi:10.1001/jamaoncol.2015.1590.
We demonstrate that thiamine deficiency does not appear to be a common
problem in patients with MPN in the United Kingdom. The data supports the
concept that development of WE for patients treated with Fedratinib, with
associated thiamine deficiency, was likely to be directly related to the drug to
date, this does not appear to be a problem associated with the other JAK
inhibitors in current clinical practice.
References
*Include patients with aspirin together with Hydroxycarbamide (3/18), venesection (2/6) and
Anagrelide (1/5). HC: hydroxycarbamide; PEG-INF: pegilated interferon, Pano:
Panobinostat; Rux: Ruxolitinib; LDE225: Sonidegib; VS: venesection; W&W: watch and
wait. Following treatments had only one patient and have not been included in this figure:
Busulfan, Erythropoietin, Lenalidomide and therapy combination with Hydroxycarbamide
and Interferon.
Overall 46 patients had Myelofibrosis (30 primary MF (PMF), 9 Post Polycythaemia Vera (PPV-MF), 6 Post Essential
Thrombocythemia (PET-MF), 23 PV, 23 ET and 1 MPN-unclassified. Median age of the cohort was 62.5 years; 44 female and 48
male patients were included. Median spleen size based on imaging was 18.5 cm (range 12-15 cm). A total of 21 patients were
receiving treatment with the JAK 1/2 inhibitor ruxolitinib, other treatments included hydroxycarbamide (n= 18); pegylated interferon
(n= 7); the combination of panobinostat and ruxolitinib (n= 7); aspirin only (n=9); venesection (n=6); anagrelide (n=5); pacritinib,
LDE225 (Sonedigib) & ruxolitinib, danazol (n= 3 each); erythropoietin, hydroxycarbarmide and interferon, lenalidomide, busulfan
(n=1 each) and finally watch & wait (n=6). No patient had evidence of thiamine deficiency. The median thiamine levels were 155.1
nmol/L (normal range 65.6-200 nmol/L). Furthermore, the thiamine levels showed no evidence of correlation with different subtypes
of MPN, different therapies or spleen size. (figure 1 A and B).
RESULTS
CONCLUSIONS
THIAMINE DEFICIENCY IS UNCOMMON IN PATIENTS
WITH MYELOPROLIFERATIVE NEOPLASMS
INTRODUCTION
Wernicke´s encephalopathy (WE) is an acute neurological syndrome characterized by an altered mental state, opthalmoplegia and
ataxia, and caused by significant deficiency of Thiamine (vitamin B1). WE is often associated with chronic alcoholism, poor
nutrition, malabsorption, or an increased metabolic requirement (e.g. in systemic malignancy). Treatment with the JAK1/2 inhibitor,
Fedratinib (Sanofi, Paris, France) was recently associated with WE and further development of Fedratinib was halted.
Figure 1B. MEDIAN THIAMINE LEVEL (nmol/l) BY TREATMENTFigure 1A. MEDIAN THIAMINE LEVEL (nmol/l) BY DISEASE
PMF: primary myelofibrosis, ET: essential thrombocythaemia, PV: polycythaemia vera,
PPVMF: post polycythaemia vera myelofibrosis, PETMF: post essential
thrombocythaemia myelofibrosis. *MPN-U: only one case for this condition, no included in
the figure. Normal thiamine range: 65-200 nmol/L.
ABSTRACT NUMBER 312
Natalia.curtogarcia@nhs.net