Chronic myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by bone marrow proliferation of one or more myeloid lineages, resulting in an overproduction of blood cells in the peripheral blood [1]. The most clinically relevant MPNs include chronic myeloid leukemia (Philadelphia chromosome-positive) and Philadelphia-negative chronic myeloproliferative neoplasms (pH– MPNs). Three classical entities are recognized within the pH– MPN category: Polycythemia vera (PV), Essential thrombocythemia (ET), and Primary myelofibrosis (PMF).

pH– MPNs are defined by the presence of driver molecular alterations that affect the JAK-STAT signaling pathway and hematopoietic growth factor receptors. These mutations, which involve the JAK2, CALR, and MPL genes, are part of the current diagnostic criteria for these disorders and are typically assessed in peripheral blood and bone marrow samples [1,2].

In 2005, the somatic p.V617F mutation in the JAK2 gene was first identified in patients with MPNs. The JAK2V617F mutation is detected in 90–95 % of patients with PV, 60 % of patients with ET and 60 % of patients with PMF. The presence of the JAK2V617F mutation was incorporated by the World Health Organization (WHO) in 2008 as a major diagnostic criterion in these three entities and remains in effect, as well as in the International Consensus Classification (ICC) of 2022 [2,3].

In late 2013, mutations in the CALR gene were identified. These mutations, which consist of insertions and deletions in exon 9 (the final exon of the gene), are detected in 25–30 % of ET and PMF patients and can be found in up to 60–80 % of JAK2-negative patients [1,2].

Several mutations affecting the gene that encodes the thrombopoietin receptor, MPL, have also been described in MPNs. These mutations occur primarily in exon 10 of the gene and are reported in about 5 % of PMF and 1–3 % of ET cases [1,2].

Although studies on pH– MPNs have been carried out in Europe and America, these disorders have a low global incidence, ranging from 1–5 cases per 100,000 inhabitants per year [2,3]. In Ecuador, there is a near-total absence of local data or published studies on pH– MPNs, which highlights the importance of investigating their frequency, diagnosis, and treatment in the country.

This study is based on information from Ecuadorian patients diagnosed with pH– MPNs from several health institutions, using data collected between 2014 and 2023. The objective is to provide a local perspective on pH– MPNs in terms of frequency, clinical presentation, diagnosis and disease evolution, using appropriate statistical methods.

This is a descriptive, observational, longitudinal, and multicenter study. Data collection was carried out by hematologists from several healthcare institutions in Ecuador between 2014 and 2023: SOLCA-Guayaquil, Quality of Care (Guayaquil), SOLCA-Quito, “José Carrasco Arteaga” Hospital (Cuenca), and Hospital “Teodoro Maldonado Carbo” (Guayaquil). The study cohort comprised 111 patients diagnosed with BCR-ABL1-negative myeloproliferative neoplasms (MPNs), specifically polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), or MPN-unclassifiable (MPN-U). Diagnoses were established according to the World Health Organization (WHO) criteria in effect at the time of each patient's initial presentation [2]. Patients who did not meet the WHO/ICC 2022 diagnostic criteria were excluded [2,3]. Data were collected using an anonymized form on a validated registry platform for this purpose (www.mpn-ecuador.com). The study was approved by the inter-institutional Ethics Committee.

Patient records included data from the date of diagnosis until death or loss to follow-up. Exclusion criteria included the absence of available bone marrow samples or missing information in the electronic registry. Histopathological analyses were performed by trained hematopathologists (FH, PS) who evaluated bone marrow biopsies when reclassification was necessary.

Epidemiological and clinical data were collected, along with information on treatments, complications, and disease progression. Statistical results are presented mainly in terms of frequencies and percentages, while quantitative variables were analyzed using univariate statistics with measures of central tendency and dispersion. A p-value of <0.05 was considered statistically significant.

Data analysis included the creation of cross-tabulation frequency tables, descriptive graphs, survival models, and Multiple Correspondence Analysis (MCA) to enable a more comprehensive exploration using multivariate visualizations. Statistical processing and analysis were conducted using R software (version 4.4.2 for Windows), available at www.r-project.org.

In this study, data on pH– MPNs patients from five hospital centers in Ecuador were reported and analyzed comparatively with other countries in the region (Central and South America).

The reviewed studies report higher prevalences of ET and PV compared to PMF. In Ecuador, PV was the most frequent (46 %), followed by ET (42 %), which aligns with findings from Cuba, Mexico, Costa Rica, Brazil, Argentina, Colombia, and Chile, where prevalences range from 38–55 % [5–13,15–18]. Peru, in contrast, reported a higher incidence of PMF [14].

Regarding age distribution, most studies concurred with our findings: pH– MPNs predominantly affect patients over 50 years old, with a peak incidence in those over 65 years in Ecuador, a pattern also reported in Chile and Brazil [5,6,11–13].

In respect to habits, 5–10 % of patients reported smoking or alcoholism in the present study and of the comorbidities, cardiovascular diseases (32 %) were the most frequently reported, with no results being found in the other countries comparing this variable.

It is important to highlight the underuse of complementary histochemical and immunohistochemical techniques. Histochemical staining should be performed on all bone marrow biopsies with suspected pH– MPN in order to evaluate fibrosis due to its importance in differential diagnosis (ET versus PMF) and prognosis (PV) [4,19,20] although recent studies have explored the application of artificial intelligence (machine learning) directly on Hematoxylin and Eosin-stained images, potentially eliminating the need for additional staining [21].

Molecular testing for the JAK2 V617F mutation is essential for the classification and prognostic evaluation of pH– MPNs; however, it was not consistently available to all patients [7–13]. Nationwide screening is limited by the low number of hospitals and laboratories offering JAK2 V617F, CALR, and MPL mutation testing, and by the limited financial resources of patients. Among those tested, the JAK2 V617F mutation was identified in 56.8 % of cases, a figure comparable to findings from Argentina (57 %), Chile (61 %), and Brazil (62 %) [5,6,11–13,15,16]. CALR and MPL mutations were less accessible and mostly reported in studies from Chile, Argentina, and Brazil [6,11–13,15,16].

In the setting of this study, triple-negative cases often face the additional limitation of not undergoing NGS to detect mutations such as ASXL1, EZH2, SRSF2, IDH1, IDH2, U2AF1 Q517 among others which are important to confirm clonality and assess prognostic implications [16].

The most frequent complications in the present study were thrombotic events (6.3 %) and hemorrhagic events (8.1 %), which are less common than those reported in the region: Chile (29 %), Colombia (14.7 %), and Brazil (12 %) [5–8,11–13].

The rate of leukemic transformation was low across the region, with similar figures to Brazil (2.8 %) [12,13]. Costa Rica reported the lowest progression rates [17].

Hydroxyurea, with or without aspirin, was the treatment most frequently used across the region. Notably, the use of JAK2 inhibitors in PMF patients is increasing in Brazil and Argentina [11–13,15–16].

In Ecuador, access to a broad therapeutic arsenal remains limited. Several drugs are either inaccessible or lack Ministry of Health authorization, including pegylated interferon alpha (for PV), anagrelide (for ET), and JAK inhibitors such as fedratinib and pacritinib (for PMF patients).

Five-year survival in Ecuador is approximately 90 %, like outcomes reported in Chile and other countries in the region [5,6,14,16].

Although the study has several limitations, such as selection bias resulting from the limited participation of most health-related institutions in the country, these data provide an initial diagnostic overview of the clinical-pathological and epidemiological status of pH– MPNs in the Ecuadorean population. The findings highlight the prevalence of PV and ET as the most common forms of pH– MPNs, with a notable presence of the JAK2 V617F mutation in these subgroups. The predominant treatment was hydroxyurea. The observed survival across the different types of pH– MPNs showed no marked variability.

These results reveal a relatively homogeneous epidemiological profile across the Latin American region and underscore the need for more multicenter studies to better characterize pH– MPNs in Ecuador and the region in order to optimize diagnostic and treatment strategies.

The data that support the findings of this study are available from the corresponding author upon reasonable request.