Developments in the management of primary myelofibrosis (PMF) have resulted in improved survival.[91]Verstovsek S, Parasuraman S, Yu J, et al. Real-world survival of US patients with intermediate- to high-risk myelofibrosis: impact of ruxolitinib approval. Ann Hematol. 2022 Jan;101(1):131-7.
https://link.springer.com/article/10.1007/s00277-021-04682-x
http://www.ncbi.nlm.nih.gov/pubmed/34625831?tool=bestpractice.com
[92]Masarova L, Bose P, Pemmaraju N, et al. Improved survival of patients with myelofibrosis in the last decade: single-center experience. Cancer. 2022 Apr 15;128(8):1658-65.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34103
http://www.ncbi.nlm.nih.gov/pubmed/35077575?tool=bestpractice.com
Median overall survival (all ages) for patients with PMF was 4.0 years, based on registry data for 3689 PMF patients diagnosed between 2001 and 2015 (median follow-up 5.8 years).[93]Smith CJ, Thomas JW, Ruan G, et al. A population-based study of outcomes in polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the United States from 2001 to 2015: comparison with data from a Mayo Clinic single institutional series. Am J Hematol. 2021 Dec 1;96(12):E464-8.
https://onlinelibrary.wiley.com/doi/10.1002/ajh.26377
http://www.ncbi.nlm.nih.gov/pubmed/34661932?tool=bestpractice.com
Retrospective data from a single centre reported an improvement in median overall survival from 48 months (95% CI, 42-54 months) in patients diagnosed in between 2000 and 2010, to 63 months (95% CI, 55-71 months) in patients diagnosed between 2011 and 2020.[92]Masarova L, Bose P, Pemmaraju N, et al. Improved survival of patients with myelofibrosis in the last decade: single-center experience. Cancer. 2022 Apr 15;128(8):1658-65.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34103
http://www.ncbi.nlm.nih.gov/pubmed/35077575?tool=bestpractice.com
The study population comprised 844 patients; median age at new diagnosis of myelofibrosis was 66 years. Those treated with ruxolitinib had a median overall survival of 84 months (95% CI, 70-94 months).[92]Masarova L, Bose P, Pemmaraju N, et al. Improved survival of patients with myelofibrosis in the last decade: single-center experience. Cancer. 2022 Apr 15;128(8):1658-65.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34103
http://www.ncbi.nlm.nih.gov/pubmed/35077575?tool=bestpractice.com
Among a cohort of 361 patients diagnosed with a myeloproliferative neoplasm between 1967 and 2017, median overall patient survival from time of diagnosis (stratified by age) was estimated to be:[94]Szuber N, Vallapureddy RR, Penna D, et al. Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am J Hematol. 2018 Dec;93(12):1474-84.
https://onlinelibrary.wiley.com/doi/10.1002/ajh.25270
http://www.ncbi.nlm.nih.gov/pubmed/30157297?tool=bestpractice.com
Adverse prognostic factors
Include age at onset (>64 years), anaemia (Hb <100 g/L [<10 g/dL]), constitutional symptoms, white blood cell count abnormalities (<4 ×10⁹/L or >12 × 10⁹/L [<4000/microlitre or >12,000/microlitre]), thrombocytopenia, circulating blast cells (>1%), and certain cytogenetic abnormalities (-5/del5q, -7/del7q, trisomy 8, 12p-).[11]Passamonti F, Cervantes F, Vannucchi AM, et al. 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. 2010 Mar 4;115(9):1703-8.
http://bloodjournal.hematologylibrary.org/cgi/content/full/115/9/1703
http://www.ncbi.nlm.nih.gov/pubmed/20008785?tool=bestpractice.com
[43]Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009 Mar 26;113(13):2895-901.
http://bloodjournal.hematologylibrary.org/content/113/13/2895.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/18988864?tool=bestpractice.com
Mutations in CALR are associated with better overall survival compared with JAK2 V617F or MPL W515 mutations.[19]Rumi E, Pietra D, Pascutto C, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014 Aug 14;124(7):1062-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133481
http://www.ncbi.nlm.nih.gov/pubmed/24986690?tool=bestpractice.com
Type 1 CALR mutations (52-bp deletion) are more common, and have a more favourable impact on prognosis than type 2 CALR mutations (5-bp insertion) in PMF.[20]Tefferi A, Nicolosi M, Mudireddy M, et al. Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN alliance study of 1,095 patients. Am J Hematol. 2018 Mar;93(3):348-55.
https://onlinelibrary.wiley.com/doi/10.1002/ajh.24978
http://www.ncbi.nlm.nih.gov/pubmed/29164670?tool=bestpractice.com
[21]Tefferi A, Lasho TL, Finke C, et al. Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia. 2014 Jul;28(7):1568-70.
https://onlinelibrary.wiley.com/doi/10.1002/ajh.24978
http://www.ncbi.nlm.nih.gov/pubmed/24569778?tool=bestpractice.com
Triple-negative mutation status (negative for JAK2, CALR, or MPL mutations) is associated with a worse prognosis in patients with PMF.[19]Rumi E, Pietra D, Pascutto C, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014 Aug 14;124(7):1062-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133481
http://www.ncbi.nlm.nih.gov/pubmed/24986690?tool=bestpractice.com
[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms [internet publication].
https://www.nccn.org/guidelines/category_1
ASXL1, EZH2, SRSF2, TP53, IDH1, IDH2, and U2AF1 mutations are considered high-molecular-risk mutations, associated with shorter overall and leukaemia-free survival.[26]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms [internet publication].
https://www.nccn.org/guidelines/category_1
[27]Rumi E, Trotti C, Vanni D, et al. The genetic basis of primary myelofibrosis and its clinical relevance. Int J Mol Sci. 2020 Nov 24;21(23):8885.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727658
http://www.ncbi.nlm.nih.gov/pubmed/33255170?tool=bestpractice.com