Age-stratiﬁed analysis reveals arterial thrombosis as a predictor for gender-related second cancers in myeloproliferative neoplasms: a case-control study

Q: How was age considered in the analysis of arterial thrombosis and second cancers?

Cases and matched controls were stratified by age at myeloproliferative neoplasm diagnosis into <60 and ≥60 years, using 60 as the cutoff to reflect conventional low- and high-risk thrombosis categories.

Q: What was the key finding regarding arterial thrombosis overall?

Arterial thrombosis occurred more frequently in patients who subsequently developed second cancer (6.2% vs 3.7%), with an elevated odds ratio on multivariable analysis.

Q: Which factors independently influenced second cancer risk in younger versus older patients?

In patients under 60, second cancer risk was independently influenced by myelofibrosis phenotype versus ET, arterial thrombosis (myocardial infarction, stroke), and was reduced by aspirin therapy. In patients over 60, no clear predictors emerged aside from a trend related to leukocytosis.

Sep 21, 2026

Uploaded by Ava Thompson

Age-stratified case-control analysis examines whether arterial thrombosis signals second cancers in patients with myeloproliferative neoplasms (PV, ET, MF). After matching for sex, age at diagnosis, date, and disease duration, investigators assess outcomes in groups <60 and ≥60 years. Arterial thrombosis frequency is higher in those who later develop second cancer, and events show distinct temporal patterns by age, with different cancer distributions. In younger patients, arterial thrombosis (including myocardial infarction, stroke) independently predicts second cancer and aspirin therapy is protective.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

To the Editor

Background and study rationale

Age-stratified design and patient characteristics

Second cancer types by age group

Thrombotic events and temporal trends

Multivariable risk factors by age

Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj) CORRESPONDENCE OPEN Age-stratiﬁed analysis reveals arterial thrombosis as a predictor for gender-related second cancers in myeloproliferative neoplasms: a case-control study © The Author(s) 2024 Blood Cancer Journal (2024)14:68; [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1038/s41408-024-01052-4](10.1038/s41408-024-01052-4) TO THE EDITOR: Over the past decade, observational and population-based studies have documented an excess of solid tumors and lymphomas inpatients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET) and myeloﬁbrosis (MF), but the causes of this excess remain elusive [1–3] . It is well known that unprovoked venous thromboembolism (VTE) may precede second cancer (SC), but the possibility that arterial thrombosis may signal impending malignancy has only recently been explored in the general population [4] . We recently investigated this association in a case-control study in the context of MPN [5, 6] and found that the frequency of arterial thrombosis in PV, ET, and MF was signiﬁcantly higher in those who subsequently developed SC (6.2% vs. 3.7%; p = 0.015) . On multivariable analysis, the odds ratio for arterial thrombosis was 1 .97 (95% CI 1 .14–3.41) [6] . To ensure comparability, the matching process between cases and controls included sex, age at MPN diagnosis, date of diagnosis, and duration of MPN disease, thus masking a possible inﬂuence of age on events and affecting the applicability of these ﬁndings across different age groups. To investigate whether the association between arterial thrombosis and SC was age-related, in the current analysis cases and matched-controls were stratiﬁed into two groups <60 or ≥60 years of age at MPN diagnosis. The age cut-off of 60 years was chosen because it conventionally represents low and high-risk categories prone to thrombosis. (i) Table 1S reports the characteristics of cases and controls inpatients stratiﬁed by age under and over 60 years. MPN cases with a SC were 647 (PV: N = 216, ET: N = 317, MF: N = 114), and MPN matched-controls were 1234 . In the under 60 group, the median age was 52 years (IQR 45–56), there was a slight preponderance of females in both cases and controls (53%), a lower percentage of ET patients in cases (50.2% vs. 58.6%, p = 0.047), a trend towards a higher frequency of patients with JAK2 mutations in cases compared to controls (74.2% vs. 67.3%, p = 0.079) as well as ASXL1 mutations (27.8% vs. 6.7%, p = 0.086) . However, the latter information was only available for 48 patients out of a total of 614 . The frequency of arterial and venous thrombosis was the same in cases and controls. No difference in cases and controls was observed inpatients over 60, except for a higher frequency of leukocytosis in cases (34.6% vs. 28.1%, p = 0.017) . Received: 6 March 2024 Revised: 9 April 2024 Accepted: 11 April 2024 (ii) Table 2S provides details of events in these two groups. The most frequent category of SC was carcinoma seen in 141 (66.2%) and 285 (65.7%) patients with age under or over 60 years, respectively. The frequency of breast, uterus, ovary, and endocrine cancer was higher in younger (p = 0.001) whereas colorectal and lung cancers prevailed in over 60 (p = 0.001 and 0.045) . The two groups showed no difference in the frequency of melanoma, non-melanoma skin cancer, and hematological malignancies. During a median follow-up of 3.6 years, cases and controls in both groups were exposed to the same cytoreductive drugs (Table 2S) . The proportion of cases under 60 years treated with low-dose aspirin was lower than controls (74.6% vs. 84.3%, p = 0.004) . Seventy thrombotic events (11.4%) were recorded in the group aged <60 years: 17 and 20 (in controls and cases, respectively) were arterial (4.2% vs. 9.4%, p = 0.011) and 75% involved the cerebral

FAQs

How was age considered in the analysis of arterial thrombosis and second cancers?

Cases and matched controls were stratified by age at myeloproliferative neoplasm diagnosis into <60 and ≥60 years, using 60 as the cutoff to reflect conventional low- and high-risk thrombosis categories.

What was the key finding regarding arterial thrombosis overall?

Arterial thrombosis occurred more frequently in patients who subsequently developed second cancer (6.2% vs 3.7%), with an elevated odds ratio on multivariable analysis.

Which factors independently influenced second cancer risk in younger versus older patients?

In patients under 60, second cancer risk was independently influenced by myelofibrosis phenotype versus ET, arterial thrombosis (myocardial infarction, stroke), and was reduced by aspirin therapy. In patients over 60, no clear predictors emerged aside from a trend related to leukocytosis.

Sep 21, 2026

Uploaded by Ava Thompson