Journal de la leucémie
Libre accès

Abstrait

Management of Calreticulin Mutated Myeloproliferative Neoplasms: Real-world Outcomes from a Low-Middle Income Country

Uzma Zaidi*, Munazza Rashid, Rifat Zubair Ahmed, Maham Fayyaz, Muhammad Nizamuddin, Nida Anwar, Gul Sufaida, Samina Naz Mukry, Munira Borhany, Tahir Sultan Shamsi

Pakistan is one of the most densely populated countries of the South-East Asian region, and rare hematological malignancies like MPNs are not uncommon, mainly attributable to the diverse ethnicity of the population which is endowed with discrete clinical and molecular characteristics. Being a low-middle income country, the scarcity of health care resources cause a delay in referrals to tertiary care hospitals especially from remote areas consequently leading to delayed diagnoses and management, resulting in dismal outcome of patients. National Institute of Blood Diseases & Bone Marrow Transplantation is the largest tertiary care hematology center where patients from all the four major provinces of Pakistan are referred for treatment. We prospectively studied the incidence, clinical behavior, treatment response, and challenges in the management of patients with CALR mutated ET and PMF in Pakistani population. The aim was to increase the understanding and knowledge of the treating physicians regarding CALR mutated MPNs across the country as well as to add to this rising body of international literature through a detailed clinicopathologic analysis of 218 MPNs.

CALR mutation was detected in 37.93% of ET and 37.25% of PMF, whereas Janus Kinase 2 (JAK2) mutation was detected in 50% of ET and 53.92% of PMF patients. 12.06% of ET and 8.82% of PMF patients were triple-negative. All CALR mutated patients received hydroxyurea as first-line agent. 45% and 31.6% patients in CALR mutated ET and PMF group respectively were switched to second line agent, interferon alpha to achieve a clinical response and significant reduction in the mean platelet count. The OS among ET and PMF patients was statistically similar in all three mutational groups. We conclude that CALR mutation analysis is crucial for the diagnosis of JAK2 negative MPN in our population as it poses clinical challenges for treating physicians due to distinct clinical characteristics and is associated with refractoriness and resistance to first line agents in considerable number of patients, though the overall survival of patients remains unchanged.