Background: Classical myeloproliferative neoplasms (MPNs); polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are diagnosed as per the WHO or ICC criteria, with incorporation of molecular genomics. In resource-limited healthcare settings, equitable access to relatively costly diagnostic genetic tests may be constrained. This leads to diagnostic uncertainty and forces physicians to make challenging clinical decisions which may not always be best for patients. Additionally, treatment algorithms are based on risk stratification which include molecular genetic criteria. This study aimed to evaluate the diagnostic conformity to 2016 WHO criteria among patients being managed as classical MPNs, and use of cytoreductive therapy among patients who do not meet diagnostic criteria.

Methods: A retrospective cross-sectional descriptive study was conducted in haematology units at National Hospital of Sri Lanka (NHSL). NHSL being the premier tertiary referral centre in the country. Patients diagnosed from January 2018 to May 2025 and being treated as PV, ET, or PMF were recruited. Information related to clinical features at presentation, diagnostic workup, laboratory findings, treatment and complications were extracted from records.

Results: A total of 125 patients, 68 (53.4%) PV, 40 (32%) ET and 17 (13.6%) PMF were enrolled. The median ages of PV, ET, and PMF patients were 55, 55.5, and 63 years, respectively. A male preponderance was observed among PV (66.2%) and PMF (70.6%). ET had an equal gender distribution.

Significant variations in diagnostic conformity were observed due to lack of molecular tests { BCR-ABL1 by PCR & MPN panel (JAK2 CALR, MPN)}. WHO 2016 criteria were met by 76.5% of PV , 23.5% of PMF and none of ET patients. In ET, BCR-ABL1 was not done in 100% and MPN panel in 30%; in PMF, BCR-ABL1 was not done in 76.4% and MPN panel in 17.6%. In PV, JAK2 and erythropoietin were not done in 16 and 14 patients, respectively.

Most patients showed symptoms described in classical MPN despite not fulfilling diagnostic criteria. Hyperviscosity symptoms were seen in PV (33.8%), ET (10%) and PMF (5.9%). Pruritus in PV (8.8%) and ET (7.5%), but not in PMF. Splenomegaly was seen in PMF (64.7%), PV (16.2%) and ET (15%). Constitutional symptoms (47.1%) and cytopenia-related symptoms (35.3%) were seen only in PMF. Thrombotic events were highest in PV (45.6%), ET (32.5%) and PMF (17.6%). Arterial events were commoner than venous. Myelofibrosis transformation in 10% of ET and 5.9% of PV.

The ET cohort had a mean follow-up of 37.5 months. Risk stratification was not possible due to lack of molecular data. 80% received hydroxycarbamide (HC) despite not fulfilling diagnostic criteria. Indications ranged from thrombosis (40.6%), age >60 years (25%) to varied manifestations (21.8%) like pruritus, refractory vasomotor symptoms, splenomegaly and extreme thrombocytosis (>1500 ×10⁹/L). No overt indication found in 4, of whom 3 developed thrombosis, bleeding, and progressed to myelofibrosis subsequently. None of the 8 untreated patients developed complications during a mean follow-up of 33 months.

The PMF cohort had a mean follow-up of 32.6 months; 6 received HC, 4 ruxolitinib, and 2 HC followed by ruxolitinib, despite lacking diagnostic criteria. Indications were symptomatic splenomegaly, constitutional symptoms, thrombosis or high white cell count.

Conclusion: This study highlights a significant shortfall in adherence to WHO diagnostic criteria among patients treated for classical MPNs in a resource-limited country with a population of about 22 million and per capita income of $3,828. The deficit was most pronounced in ET and PMF, as molecular testing was limited due to financial restraints. Physicians managing these patients are faced with the arduous task of making clinical decisions, especially regarding starting cytoreductive therapy based on clinical and hematological features. Sometimes they hinge their decisions on personal experience or fall back to diagnostic criteria and treatment algorithms from the pre-molecular diagnostics era. Based on these a probable diagnosis is made. It would be prudent to conduct a prospective study on a large cohort of patients with probable diagnoses of MPN in resource limited settings to compare risks versus benefits of cytoreductive therapy in each of the 3 conditions.

This content is only available as a PDF.
2025
Sign in via your Institution