PB2042: CLINICAL AND MOLECULAR CORRELATION OF PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: A RETROSPECTIVE ANALYSIS FROM A TERTIARY CARE CENTER IN INDIA.

Abstract

Background: Approximately 50–70% of patients of ET harbor JAK2 mutation while about 20–30% patients carry CALR mutations. Data from developed countries has shown that CALR mutated patients have higher platelet count and lower thrombotic risk compared to JAK2 mutated patients. In India, testing for CALR and MPL mutation and next generation sequencing has become available only in last 5 years. There is lack of data regarding mutation status and its clinical correlation. We studied clinical features of ET patients presented to our hospital according to their mutation status. Aims: To study the molecular mutations and correlate them with the clinical features in ET patients Methods: We did the retrospective analysis of the patients diagnosed as ET from January 2016 to December 2021. Allele Specific PCR and fragment analysis was done to detect JAK2 (V617F), MPL (W515L/K) and CALR exon-9 mutations. Risk stratification done as per revised IPSET (International Prognostic Scoring for thrombosis in Essential Thrombocythemia) score. Therapy was started in all the patients according to their risk score with hydroxyurea or aspirin as the standard of care. Results: A total of 39 diagnosed cases of ET were identified. Median age was 55 years (30-83), 20/39 males (51.3%) and 19/39 females (48.7%). JAK2 mutation was found in 25.6% (10/39), CALR in 38.5% (15/39) and MPL in 5.1% (2/39) cases. Triple negativity was found in 30.8% (12/39) cases. Very low, low, intermediate and high-risk patients as per IPSET score were 53.9% (21/39), 10.2% (4/39), 20.5% (8/39) and 15.4% (6/39) respectively. The median age was statistically significantly lower in CALR positive cases compared to the JAK2 positive cases (45.9 vs 60.9years, p=0.011). The median Hemoglobin and platelet counts were slightly higher in CALR positive group (12.3 g/dL and 10.15x109/l) compared to JAK2 mutated and triple negative groups but the difference was not statistically significant. Three patients (7.7%) presented with thrombosis; two with cerebral venous thrombosis both CALR positive, one with arterial stroke and MPL gene mutation. Ten (25.6%) patients were lost to follow up. One (2.6%) died to pulmonary infection. Median follow up period was 24 months. None of the patient transformed to acute myeloid leukemia or myelofibrosis. None of the patient developed thrombotic event after diagnosis and appropriate treatment. Summary/Conclusion: We observed that CALR was the most common mutation in our study. The CALR mutated patients were younger in age but the median platelet counts, WBC count and Hemoglobin were not statistically different among different mutation groups. In contrast to western studies, thrombosis was observed to be higher in CALR mutated group than others in our patient population. We recommend larger multicenter study for further elucidation of these observations.