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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study

Leukemia volume 38, pages 570–578 (2024)Cite this article

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Abstract

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

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Fig. 1: Survival by Diagnosis.
Fig. 2: Thrombosis-Free Survival In ET.
Fig. 3: Outcomes of patients with PMF.
Fig. 4: Impact of additional mutations (excluding MPN-driver mutations) in AYA patients with MPN.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Spivak JL. Myeloproliferative neoplasms. N Engl J Med. 2017;376:2168–81.

    Article  CAS  PubMed  Google Scholar 

  2. Segura-Díaz A, Stuckey R, Florido Y, González-Martín JM, López-Rodríguez JF, Sánchez-Sosa S, et al. Thrombotic risk detection in patients with polycythemia vera: the predictive role of DNMT3A/TET2/ASXL1 mutations. Cancers. 2020;12:934.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29:392–7.

    Article  PubMed  Google Scholar 

  4. Grinfeld J, Nangalia J, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R, et al. Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med. 2018;379:1416–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tefferi A, Guglielmelli P, Lasho TL, Gangat N, Ketterling RP, Pardanani A, et al. MIPSS70+ version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol. 2018;36:1769.

    Article  PubMed  Google Scholar 

  6. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123:2220–8.

    Article  CAS  PubMed  Google Scholar 

  7. Tefferi A, Guglielmelli P, Lasho TL, Coltro G, Finke CM, Loscocco GG, et al. Mutation‐enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera. Br J Haematol. 2020;189:291–302.

    Article  CAS  PubMed  Google Scholar 

  8. Hofmann I. Myeloproliferative neoplasms in children. J Hematopathol. 2015;8:143–57.

    Article  MathSciNet  Google Scholar 

  9. Szuber N, Vallapureddy RR, Penna D, Lasho TL, Finke C, Hanson CA, et al. Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am J Hematol. 2018;93:1474–84.

    Article  CAS  PubMed  Google Scholar 

  10. Kucine N. Myeloproliferative neoplasms in children, adolescents, and young adults. Curr Hematol Malig Rep. 2020;15:141–8.

  11. Kucine N, Al‐Kawaaz M, Hajje D, Bussel J, Orazi A. Difficulty distinguishing essential thrombocythaemia from polycythaemia vera in children with JAK 2 V617F‐positive myeloproliferative neoplasms. Br J Haematol. 2019;185:136–9.

    Article  PubMed  Google Scholar 

  12. Ishida H, Miyajima Y, Hyakuna N, Hamada S, Sarashina T, Matsumura R, et al. Clinical features of children with polycythemia vera, essential thrombocythemia, and primary myelofibrosis in Japan: a retrospective nationwide survey. eJHaem. 2020;1:86–93.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Karow A, Nienhold R, Lundberg P, Peroni E, Putti M, Randi M, et al. Mutational profile of childhood myeloproliferative neoplasms. Leukemia 2015;29:2407–9.

    Article  CAS  PubMed  Google Scholar 

  14. Barzilai M, Kirgner I, Avivi I, Ellis M, Dally N, Rozovski U, et al. Characteristics and outcomes of young adults with Philadelphia‐negative myeloproliferative neoplasms. Eur J Haematol. 2019;102:504–8.

    Article  PubMed  Google Scholar 

  15. Boddu P, Masarova L, Verstovsek S, Strati P, Kantarjian H, Cortes J, et al. Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms. Ann Hematol. 2018;97:109–21.

    Article  PubMed  Google Scholar 

  16. Stein BL, Saraf S, Sobol U, Halpern A, Shammo J, Rondelli D, et al. Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leuk lymphoma. 2013;54:1989–95.

    Article  CAS  PubMed  Google Scholar 

  17. Sant’Antonio E, Borsani O, Camerini C, Botta C, Santoro M, Allegra A, et al. Philadelphia chromosome-negative myeloproliferative neoplasms in younger adults: a critical discussion of unmet medical needs, with a focus on pregnancy. Blood Rev. 2022;52:100903.

    Article  PubMed  Google Scholar 

  18. Devlin R, Gupta V. Myelofibrosis: to transplant or not to transplant? Hematol Am Soc Hematol Educ Program Book. 2016;2016:543–51.

    Article  Google Scholar 

  19. Cario H, McMullin MF, Pahl HL. Clinical and hematological presentation of children and adolescents with polycythemia vera. Ann Hematol 2009;88:713–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ianotto J-C, Curto-Garcia N, Lauermanova M, Radia D, Kiladjian J-J, Harrison CN. Characteristics and outcomes of patients with essential thrombocythemia or polycythemia vera diagnosed before 20 years of age: a systematic review. Haematologica 2019;104:1580–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Palandri F, Latagliata R, Polverelli N, Tieghi A, Crugnola M, Martino B, et al. Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis. Leukemia 2015;29:1344–9.

    Article  CAS  PubMed  Google Scholar 

  22. England JT, McNamara CJ, Kennedy JA, Capo-Chichi J-M, Huang J, Arruda A, et al. Clinical and molecular correlates of JAK-inhibitor therapy failure in myelofibrosis: long-term data from a molecularly annotated cohort. Leukemia 2022;36:1689–92.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 2017;19:4–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018;32:1057–69.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Cazzola M, et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood, J Am Soc Hematol 2010;116:2857–8.

    CAS  Google Scholar 

  26. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization–essential thrombocythemia (IPSET-thrombosis). Blood, J Am Soc Hematol 2012;120:5128–33.

    CAS  Google Scholar 

  27. Barbui T, Vannucchi AM, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J 2015;5:e369–e.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol 2014;34:2363–71.

    Article  CAS  PubMed  Google Scholar 

  29. Williams N, Lee J, Moore L, Baxter JE, Hewinson J, Dawson KJ, et al. Driver mutation acquisition in utero and childhood followed by lifelong clonal evolution underlie myeloproliferative neoplasms. Blood 2020;136:LBA–1.

    Article  Google Scholar 

  30. Farina M, Russo D, Hoffman R. The possible role of mutated endothelial cells in myeloproliferative neoplasms. haematologica 2021;106:2813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Reeves BN, Beckman JD. Novel pathophysiological mechanisms of thrombosis in myeloproliferative neoplasms. Curr Hematol Malig Rep. 2021;16:304–13.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Williams N, Lee J, Mitchell E, Moore L, Baxter EJ, Hewinson J, et al. Life histories of myeloproliferative neoplasms inferred from phylogenies. Nature 2022;602:162–8.

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Chu DK, Hillis CM, Leong DP, Anand SS, Siegal DM. Benefits and risks of antithrombotic therapy in essential thrombocythemia: a systematic review. Ann Intern Med. 2017;167:170–80.

    Article  PubMed  Google Scholar 

  34. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood, J Am Soc Hematol. 2014;123:2220–8.

    CAS  Google Scholar 

Download references

Acknowledgements

This work was organized through the Canadian MPN Group and supported by grants from the Princess Margaret Cancer Centre Foundation and the Elizabeth and Tony Comper Foundation to the MPN Program at the Princess Margaret Cancer Centre.

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Authors and Affiliations

  1. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

    James T. England, Verna Cheung, Karine Gauthier, Hassan Sibai, Marta B. Davidson, Aniket Bankar, Vikas Gupta & Dawn Maze

  2. Division of Medical Oncology & Malignant Hematology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    James T. England

  3. Maisonneuve-Rosemont Hospital, University of Montreal, Quebec, QC, Canada

    Natasha Szuber

  4. Jewish General Hospital, McGill University, Montreal, QC, Canada

    Shireen Sirhan

  5. Division of Hematology, Newfoundland and Labrador Health Services, St. John’s, NL, Canada

    Tom Dunne

  6. Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada

    Sonia Cerquozzi

  7. The Ottawa Hospital Research Institute, Ottawa, Ottawa, ON, Canada

    Madeleine Hill & Pierre J. A. Villeneuve

  8. The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada

    Pierre J. A. Villeneuve

  9. Division of Hematology, Department of Medicine, Western University, London Health Sciences Centre, London, ON, Canada

    Jenny M. Ho

  10. Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada

    Bekim Sadikovic & Pratibha Bhai

  11. Royal Victoria Regional Health Center, Barrie, ON, Canada

    Nupur Krishnan & Rouslan Kotchetkov

  12. Department of Oncology, McMaster University, Hamilton, ON, Canada

    Sebastian Dowhanik & Chris Hillis

  13. Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

    Jose-Mario Capo-Chichi

  14. Department of Hematopathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Hubert Tsui

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Contributions

RK and DM conceived of the study idea; JTE, NS, SS, SC, PV, KH, CH, VC, KG, HS, MBD, AB, RK, VG, and DM contributed to clinical patient management; JTE, NS, SS, TD, MH, NK, and SD collected the clinical data; BS, PB, JMCC, and HT analyzed and annotated the mutational data; JTE performed the statistical analyses; JTE and DM wrote the manuscript; DM supervised the study and was overall responsible for the conduct of the study. All authors reviewed the manuscript and affirmed for publication.

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Correspondence to James T. England.

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Competing interests

JTE, NS, SS, TD, SC, MH, PJAV, JMH, BS, PB, NK, SD, CH, JMCC, HT, VC, KG, HS, MBD, AB, and RK report no conflicts or competing interests to declare. VG has received research funding through his institution and honoraria from Novartis and Incyte and has served on the advisory board of Novartis, Incyte, BMS-Celgene, Abb Vie, Sierra Oncology, Pfizer, Takeda, and Constellation Biopharma. DM has received search support from Novartis, Celgene/BMS, PharmaEssentia, Takeda; honoraria from Novartis, Celgene/BMS; and has served in consultation or on the advisory board for Novartis and Pfizer.

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England, J.T., Szuber, N., Sirhan, S. et al. Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study. Leukemia 38, 570–578 (2024). https://doi.org/10.1038/s41375-024-02155-4

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