Citation: British Journal of Haematology. 2019, 185, 58-9
Author: Lindsay K.R.; Butt N.M.; Miller K.
Abstract: The updated British Society for Haematology (BSH) guidelines on the diagnosis and management of polycythaemia vera (2018) recommend testing for JAK2 exon 12 mutations in patients with significant JAK2-unmutated erythrocytosis who have low or normal serum erythropoietin (EPO) levels. Our regional molecular genetics service perform JAK2 exon 12 mutation screening based on clinician request without the requirement of EPO-based stratification. In the light of the updated BSH guidance, we retrospectively reviewed a serial cohort of cases of polycythaemia referred for JAK2 mutation screening to determine if adopting an EPO-based algorithm for JAK2 exon 12 mutation screening would significantly alter the number of cases referred for testing. This could have implications on the clinical appropriateness of JAK2 exon 12 mutation screening and may contribute to cost savings. Our regional molecular genetics service provided details of 207 serial regional cases referred for JAK2 V617F testing between February 2018 and October 2018 with clinical details indicating suspected polycythaemia. Twenty-one of the 207 cases were positive for a JAK2 V617F mutation (10%). The majority of JAK2 V617F negative cases (122) did not have any further molecular testing performed, presumably due to the lack of suspicion of a primary polycythaemia. The remaining 64 JAK2 V617F negative cases went on to have JAK2 exon 12 mutation screening. None of these cases were identified to have JAK2 exon 12 mutations. To determine the role of a possible EPO-based stratification for JAK2 exon 12 mutation screening, EPO levels were sought for these 64 cases. Results were available for 51 of these cases. Seven cases had low EPO levels, 42 had levels in the normal range and the two remaining cases had high EPO levels. This confirms that at least two cases were tested for JAK2 exon 12 mutations which would not be indicated if based on the updated BSH guidelines. Assuming the same proportion of cases with high EPO levels (2/51) were found in the remaining 13 cases where EPO levels were not available, this equates to a further 0.51 cases. Based on 2.51 cases tested for JAK2 exon 12 mutations outside of the updated BSH guidelines, at the current cost of 150.00 per JAK2 exon 12 mutation screen, this equates to a cost saving of 376.50. Whilst any cost savings for unnecessary molecular tests are creditable, we do not currently believe that our regional molecular genetics service should withhold JAK2 exon 12 mutation screening in the absence of a EPO-based stratification given that the vast majority of cases will have normal or low results. Finally, a point of interest discovered in the process of this audit was that regardless of the EPO level there were no cases where an exon 12 mutation was detected. Indeed, when our regional molecular genetics service reviewed all requests for JAK2 exon 12 mutation screening since testing for this began in 2008, out of more than 500 cases tested only one mutation was identified, in 2016. Of note is that this patient had a serum EPO level in the normal range. Requests for exon 12 testing continue to increase annually with more than 100 cases tested in each of the last two calendar years. This confirms the high overall cost of screening for exon 12 mutations in suspected primary polycythaemia in JAK2 V617F negative cases given their very low prevalence.
