Myeloproliferative Neoplasms Linked With Respiratory Mortality, Study Says

Patients with myeloproliferative neoplasm have roughly twice the risk of pneumonia and respiratory mortality, according to a major new study.

The research helps shed light on a comorbidity category that had previously been little understood in this patient population. The results are published in the journal EClinicalMedicine.

Myeloproliferative neoplasms are a category of rare blood cancers with different but overlapping cellular, molecular, and clinical alterations, according to corresponding author Stig Egil Bojesen, MD, of Copenhagen University Hospital, in Denmark, and colleagues. Patients with these cancers often have high rates of comorbidities, including cardiovascular and thromboembolic diseases. Anecdotal case reports have examined respiratory comorbidities in such patients; however, a large-scale study had not been done to date.

Bojesen and colleagues decided to investigate the question using a large-scale prospective study of Danish residents ages 20 and older. From 2003 to 2015, the team recruited 107,900 patients, who were enrolled in the Copenhagen General Population Study. All enrollees were examined for lung function and respiratory symptoms at the start of the study, and then followed through 2018 in order to calculate the risk of pneumonia and respiratory mortality using a Cox proportional hazard regression.

Within the cohort, 351 patients were diagnosed with myeloproliferative neoplasms, about one-third (131) of whom were diagnosed at baseline and the rest diagnosed during the course of the study. The latter group was evaluated using a time-varying variable to account for the later diagnosis. Among the 351 patients with myeloproliferative neoplasms, 125 patients (36%) of the patients had essential thrombocythemia; 124 patients (35%) had polycythaemia vera; and 102 (29%) had myelofibrosis or unclassifiable myeloproliferative neoplasms.

Compared to the control group without myeloproliferative neoplasms, those with the cancers had multivariable adjusted hazard ratios of 2.18 for pneumonia and 2.27 for respiratory mortality. However, most of the increased risk was in patients with polycythaemia vera and myelofibrosis or unclassifiable myeloproliferative neoplasms. Bojesen and colleagues said results were similar in patients with and without airflow limitations, and in those who did and did not smoke.

Bojesen and colleagues said the causes for the link between myeloproliferative neoplasm and respiratory diseases could be related both to the cancer itself or to therapies for the cancer.

In the former category, the investigators said alterations in the bone marrow of patients ought to be considered as a factor. They write that less functional bone marrow in these patients could lead to displacement and mobilization of stem and progenitor cells. In the blood circulation such cells could be deposited and activated in different organ systems.

“Activation of stem and progenitor cells may lead to release of cytokines and growth factors, e.g. pro-inflammatory and pro-fibrotic cytokines, which may lead to chronic low-grade inflammation,” they write. “Such stem and progenitor cells can be deposited and activated in the pulmonary compartment affecting the lungs and/or pulmonary defense mechanisms against microorganisms.”

The authors also note that patients with myeloproliferative neoplasms are treated with cytoreductive agents, which they note could have toxic effects on certain organ systems.

Bojesen and colleagues say these findings, and the potential for treatment to be one cause, ought to be one factor considered when devising therapeutic plans for patients.

Reference

Pedersen KM, Çolak Y, Hasselbalch HC, Ellervik C, Nordestgaard BG, Bojesen SE. Two-fold risk of pneumonia and respiratory mortality in individuals with myeloproliferative neoplasm: A population-based cohort study. EClinicalMedicine. 2020;21:100295. doi:10.1016/j.eclinm.2020.100295.