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Young patients with myelofibrosis have distinct clinicomolecular features, favorable prognosis, and commonly exhibit inflammatory comorbidities

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Abstract

Myelofibrosis (MF) is commonly diagnosed in older individuals and has not been extensively studied in young patients. Given the infrequent diagnosis in young patients, analyzing this cohort may identify factors that predict for disease development/progression. We retrospectively analyzed clinical/genomic characteristics, treatments, and outcomes of patients with MF aged 18–50 years (YOUNG) at diagnosis. Sixty-three YOUNG patients were compared to 663 patients diagnosed at 51 or older (OLDER). YOUNG patients were more likely to be female, harbor driving CALR mutations, lack splicing gene mutations, and have low-risk disease by dynamic international prognostic scoring system (DIPSS) at presentation. Thirty-six patients (60%) presented with incidental lab findings and 19 (32%) with symptomatic disease. Median time to first treatment was 9.4 months (mo). Fourteen (22%) YOUNG patients underwent allogeneic hematopoietic stem cell transplant (median 57.4 mo post-diagnosis). Five (8%) developed blast-phase disease (median 99 mo post-diagnosis). Median overall survival (OS) for YOUNG patients was not reached compared to 62.8 mo in OLDER cohort (p < 0.001). The survival advantage for YOUNG patients lost significance when compared to OLDER patients lacking splicing mutations (p = 0.11). Thirty-one (49%) had comorbidities predating MF diagnosis. Presence of a comorbidity correlated with increased disease risk as measured by serial DIPSS (p=0.02). Increased disease risk correlated with decreased OS (p = 0.05). MF is rare in young adults, has distinct clinical/molecular correlates, and a favorable prognosis. The high frequency of inflammatory comorbidities and their correlation with progression of disease risk clinically highlights the role of inflammation in MF pathogenesis.

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Data availability

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

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Authors and Affiliations

  1. University of South Florida Health Morsani College of Medicine, 560 Channelside Dr., Tampa, FL, 33602, USA

    Nathan P. Horvat

  2. Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA

    Enas F. Abdallah, Zhuoer Xie, Najla Al Ali, Seongseok Yun, Alison Walker, Eric Padron, David Sallman, Onyee Chan, Jeffrey Lancet, Rami Komrokji & Andrew T. Kuykendall

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  1. Nathan P. Horvat
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Contributions

NPH and ATK designed the study, analyzed the data, and wrote the manuscript. ENF provided data analysis, interpretation, and critical revision. NAA collected and analyzed data. ZX, SY, AW, EP, DS, OC, JL, and RK provided patient data and critical revision of the manuscript.

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Correspondence to Andrew T. Kuykendall.

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Horvat, N.P., Abdallah, E.F., Xie, Z. et al. Young patients with myelofibrosis have distinct clinicomolecular features, favorable prognosis, and commonly exhibit inflammatory comorbidities. Ann Hematol 103, 117–123 (2024). https://doi.org/10.1007/s00277-023-05564-0

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