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.
Similar content being viewed by others
Data availability
The data that support the findings of this study are available from the corresponding author (ATK) upon reasonable request.
References
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951
Tefferi A (2021) Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 96(1):145–162
Boddu P, Masarova L, Verstovsek S, Strati P, Kantarjian H, Cortes J et al (2018) Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms. Ann Hematol 97(1):109–121
Iurlo A, Cattaneo D, Gianelli U (2019) Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options. Int J Mol Sci 20(8):1839
Rampal R, Al-Shahrour F, Abdel-Wahab O, Patel JP, Brunel J-P, Mermel CH et al (2014) Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood 123(22):e123–ee33
Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A et al (2010) A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 115(9):1703–1708
Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH et al (2014) CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 28(7):1472–1477
Barzilai M, Kirgner I, Avivi I, Ellis M, Dally N, Rozovski U et al (2019) Characteristics and outcomes of young adults with Philadelphia-negative myeloproliferative neoplasms. Eur J Haematol 102(6):504–508
Beauverd Y, Alimam S, McLornan DP, Radia DH, Harrison CN (2016) Disease characteristics and outcomes in younger adults with primary and secondary myelofibrosis. Br J Haematol 175(1):37–42
Szuber N, Vallapureddy RR, Penna D, Lasho TL, Finke C, Hanson CA et al (2018) Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am J Hematol 93(12):1474–1484
Palandri F, Latagliata R, Polverelli N, Tieghi A, Crugnola M, Martino B et al (2015) Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis. Leukemia 29(6):1344–1349
Barbui T, Thiele J, Carobbio A, Passamonti F, Rumi E, Randi ML et al (2012) Disease characteristics and clinical outcome in young adults with essential thrombocythemia versus early/prefibrotic primary myelofibrosis. Blood 120(3):569–571
Shalev O, Goldfarb A, Ariel I, Rachmilewitz E (1983) Myelofibrosis in young adults. Acta Haematol 70(6):396–399
Prins D, González Arias C, Klampfl T, Grinfeld J, Green AR (2020) Mutant Calreticulin in the Myeloproliferative Neoplasms. Hemasphere 4(1):e333
Barosi G, Berzuini C, Liberato LN, Costa A, Polino G, Ascari E (1988) A prognostic classification of myelofibrosis with myeloid metaplasia. Br J Haematol 70(4):397–401
Cervantes F, Pereira A, Esteve J, Rafel M, Cobo F, Rozman C et al (1997) Identification of ‘short-lived’ and ‘long-lived’ patients at presentation of idiopathic myelofibrosis. Br J Haematol 97(3):635–640
Reilly JT, Snowden JA, Spearing RL, Fitzgerald PM, Jones N, Watmore A et al (1997) Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol 98(1):96–102
Tefferi A, Mesa RA, Schroeder G, Hanson CA, Li C-Y, Dewald GW (2001) Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia. Br J Haematol 113(3):763–771
Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S et al (2008) Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia 22(2):437–438
Quintás-Cardama A, Kantarjian H, Pierce S, Cortes J, Verstovsek S (2013) Prognostic Model to Identify Patients With Myelofibrosis at the Highest Risk of Transformation to Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk 13(3):315–8.e2
Cervantes F, Tassies D, Salgado C, Rovira M, Pereira A, Rozman C (1991) Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients. Acta Haematol 85(3):124–127
Kristinsson SY, Landgren O, Samuelsson J, Bjorkholm M, Goldin LR (2010) Autoimmunity and the risk of myeloproliferative neoplasms. Haematologica. 95(7):1216–1220
Bak M, Jess T, Flachs EM, Zwisler AD, Juel K, Frederiksen H (2020) Risk of inflammatory bowel disease in patients with chronic myeloproliferative neoplasms: a Danish nationwide cohort study. Cancers (Basel) 12(9):2700
Jayasuriya NA, Kjaergaard AD, Pedersen KM, Sorensen AL, Bak M, Larsen MK et al (2020) Smoking, blood cells and myeloproliferative neoplasms: meta-analysis and Mendelian randomization of 2.3 million people. Br J Haematol 189(2):323–334
Leiba A, Duek A, Afek A, Derazne E, Leiba M (2017) Obesity and related risk of myeloproliferative neoplasms among israeli adolescents. Obesity (Silver Spring) 25(7):1187–1190
Baumeister J, Chatain N, Sofias AM, Lammers T, Koschmieder S (2021) Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives. Cells 10(12):3551
Gecht J, Tsoukakis I, Kricheldorf K, Stegelmann F, Klausmann M, Griesshammer M et al (2021) Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry. Cancers 13(16):4086
Lucijanic M, Galusic D, Krecak I, Sedinic M, Holik H, Perisa V et al (2020) Reduced renal function strongly affects survival and thrombosis in patients with myelofibrosis. Ann Hematol 99(12):2779–2785
Hasselbalch HC (2013) Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development? Leuk Res 37(2):214–220
Fisher DAC, Fowles JS, Zhou A, Oh ST (2021) Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms. Front Immunol 12:683401
Lussana F, Rambaldi A (2017) Inflammation and myeloproliferative neoplasms. J Autoimmun 85:58–63
Mendez Luque LF, Blackmon AL, Ramanathan G, Fleischman AG (2019) Key Role of Inflammation in Myeloproliferative Neoplasms: Instigator of Disease Initiation, Progression. and Symptoms. Curr Hematol Malig Rep 14(3):145–153
Masselli E, Pozzi G, Gobbi G, Merighi S, Gessi S, Vitale M et al (2020) Cytokine Profiling in Myeloproliferative Neoplasms: Overview on Phenotype Correlation, Outcome Prediction, and Role of Genetic Variants. Cells 9(9):2136
Samuelson BT, Vesely SK, Chai-Adisaksopha C, Scott BL, Crowther M, Garcia D (2016) The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood Coagul Fibrinolysis 27(6):648–652
Author information
Authors and Affiliations
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.
Corresponding author
Ethics declarations
Human ethics and consent to participate
Not applicable.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-023-05564-0