Distinctive Attributes of Indian Patients With Classical BCR::ABL1 Negative Myeloproliferative Neoplasms: Unified Clinical and Laboratory Data

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2023-05, Vol.23 (5), p.360-369.e1
• Main Authors: Singh, Suvir, Singh, Jagdeep, Mehta, Arpan, Sharma, Rintu, Joshi, Kaveri, Jain, Kunal, Paul, Davinder, Oberoi, Gurleen, Jindal, Nandita, Dhillon, Barjinderjit, Narang, Vikram
• Format: Article
• Language: English
• Subjects: Calreticulin - genetics; Humans; Janus Kinase 2 - genetics; Molecular; Mutation; Myelofibrosis; Myeloproliferative; Myeloproliferative Disorders - diagnosis; Myeloproliferative Disorders - genetics; NGS; Polycythemia; Polycythemia Vera - diagnosis; Primary Myelofibrosis - diagnosis; Primary Myelofibrosis - genetics; Primary Myelofibrosis - pathology; Receptors, Thrombopoietin - genetics; Thrombosis
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2023.01.012

We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n = 5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models. We report clinical and molecular features of Indian patients with BCR:ABL1 negative MPNs. A relatively lower symptom burden at diagnosis, younger age of onset and low burden of thrombosis indicates a comparatively indolent presentation. Several novel mutations on 1 of the largest NGS datasets in Indian patients are also reported. A summary of recommended considerations for clinical practice is provided.