Skip to main content

Advertisement

SpringerLink
Log in

Approach to MPN Symptom Assessment

  • Myeloproliferative Neoplasms (B Stein, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Myeloproliferative neoplasms (MPNs) are recognized for their debilitating symptom burdens. The purpose of this review is to understand the complexity of the MPN symptom burden and identify how validated MPN Patient Reported Outcome (PRO) tools may be integrated into clinical practice to assess the MPN symptom burden.

Recent Findings

Significant heterogeneity exists both within and between MPN subtypes. Surrogates of disease burden such as risk scores and MPN chronicity often fail to correlate with symptomatic burden. Validated MPN PROs allow for precise and rapid assessment of the MPN symptom burden in clinical and trial settings. Their growing use among investigators has resulted in improved understanding of how the MPN disease burden and overall patient experience is impacted by novel and traditional therapies.

Summary

PRO tools are an integral part of National Comprehensive Cancer Center (NCCN) guidelines for MPN treatment and should be regularly employed in disease burden assessment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6(4):372–5.

    CAS  PubMed  Google Scholar 

  2. Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13. quiz 615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Passamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentini M, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117(10):755–61.

    Article  PubMed  Google Scholar 

  4. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93.

    Article  PubMed  Google Scholar 

  5. •• Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–81. This is the most commonly used prognostic scoring system for PV.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131(2):208–13.

    Article  CAS  PubMed  Google Scholar 

  7. 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. 2012;120(26):5128–33. quiz 252

  8. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.

    Article  CAS  PubMed  Google Scholar 

  10. Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472–7.

    Article  CAS  PubMed  Google Scholar 

  11. 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(4):392–7.

    Article  PubMed  Google Scholar 

  12. Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, et al. The myeloproliferative neoplasm symptom assessment form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011;118(2):401–8.

    Article  CAS  PubMed  Google Scholar 

  13. •• National Comprehensive Cancer Network Guidelines: myeloproliferative neoplasms. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed June 16th, 2017. These were the first guidelines to introduce symptom burden assessment as part of routine evaluation of MPN patients.

  14. Geyer HL, Scherber RM, Dueck AC, Kiladjian JJ, Xiao Z, Slot S, et al. Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients. Blood. 2014;123(24):3803–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. • Geyer HL, Andreasson B, Kosiorek HE, Dueck AC, Scherber RM, Martin KA, et al. The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: an analysis by the MPN QOL international study group. Cancer. 2016;122(12):1888–96. This study was among the first demonstrating the multifactorial nature of MPN symptom development.

  16. • Geyer HL, Dueck AC, Emanuel RM, Cannon K, Kiladjian J-J, Slot S, et al. Insomnia, quality of life and MPN symptom burden: an analysis by the MPN quality of life international study group (MPN-QOL ISG). Blood. 2013;122(21):4087. This was the first article to demonstrate differences in symptomatic burden by patient gender.

    Google Scholar 

  17. Geyer HL, Kosiorek H, Dueck AC, Scherber R, Slot S, Zweegman S, et al. Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL international working group. Haematologica. 2017;102(1):85–93.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Geyer HL, Scherber RM, Dueck AC, Kiladjian JJ, Xiao Z, Slot S, et al. Symptom severity and clinical variables of polycythemia vera patients with splenomegaly, phlebotomy requirements and/or hydroxyurea use: a retrospective evaluation of 1334 patients. Blood ASH Annual Meeting 2014;124(21).

  19. Emanuel R, Marchioli R, Dueck A, Geyer HL, Finazzi G, Cavazzina R, Masciulli, A, et al. Impact of hematocrit on symptom burden among polycythemia vera patients. European Hematology Association Annual Meeting Abstracts 2013;276.

  20. Geyer H, Scherber RM, Kosiorek H, Dueck AC, Kiladjian J-J, Xiao Z, et al. Symptom burden profile in myelofibrosis patients with thrombocytopenia: lessons and unmet needs. Blood. 2015;126:4080.

    Google Scholar 

  21. • Dueck AC, Cleeland CS, Dantzer R, Sloan J, Verstovsek S, Emanuel RM, et al. Cytokine profile changes in 309 myelofibrosis patients: comparison of JAK1/JAK2 inhibitor therapy vs. placebo—correlative analysis from the Comfort-I trial. Blood. 2013;122(21):4074. This was the first publication documenting changes in the MPN symptom burden over time by individual symptoms.

    Google Scholar 

  22. • Scherber RM, Geyer H, Harrison CN, Kosiorek HE, Dueck AC, Kiladjian J-J, et al. Impact of disease duration upon symptom burden amongst patients with myeloproliferative neoplasms (MPNs). Blood. 2015;126:4073. In this investigation, it was demonstrated that length of disease is not necessarily a determinant of MPN disease severity.

  23. Mesa RA, Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer. 2007;109(1):68–76.

    Article  PubMed  Google Scholar 

  24. Mesa RA, Schwager S, Radia D, Cheville A, Hussein K, Niblack J, et al. The myelofibrosis symptom assessment form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33(9):1199–203.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Emanuel RM, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol. 2012;30(33):4098–103.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Eremenco S, Oko-Osi H, Arnold B, Savic L, Sterling K, Athearn R, et al. Translation and linguistic validation of the modified myeloproliferative neoplasm symptom assessment form—total symptom score (MMPN-SAF TSS) for use in 26 countries. Value Health. 2015;18(7):A471–2.

    Article  CAS  PubMed  Google Scholar 

  27. Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643–51.

    Article  PubMed  Google Scholar 

  28. •• Mesa R, Vannucchi AM, Yacoub A, Zachee P, Garg M, Lyons R, et al. The efficacy and safety of continued hydroxyurea therapy versus switching to ruxolitinib in patients with polycythemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF). Blood. 2014;124(21):3168. This was among the first publcations demonstraing the impact of JAK2 inhibition on PV symptoms.

    Google Scholar 

  29. Mesa RA, Kantarjian H, Tefferi A, Dueck A, Levy R, Vaddi K, et al. Evaluating the serial use of the myelofibrosis symptom assessment form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer. 2011;117(21):4869–77.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Emanuel R, Dueck AC, Geyer HL, Kiladjian J-J, Slot S, Zweegman S, et al. Myeloproliferative (MPN) symptom burden response thresholds: assessment of MPN-SAF TSS quartiles as potential markers of symptom response. Blood. 2013;122:4067.

    Google Scholar 

  32. Scherber R, Dueck A, Geyer HL, Kosiorek H, Kiladijan JJ, Slot S, et al. Symptoms, risk classification and spleen size in JAK2 inhibitor-naive myelofibrosis: Implications for JAK2 inhibitor treatment. European Hematology Association Annual Meeting Abstracts: E1345.

  33. •• Scherber RM, Kosiorek HE, Senyak Z, Dueck AC, Clark MM, Boxer MA, et al. Comprehensively understanding fatigue in patients with myeloproliferative neoplasms. Cancer. 2016;122(3):477–85. This investigation comprehensively reviewed the the prevalent and burdensome MPN symptom of fatigue.

    Article  PubMed  Google Scholar 

  34. Mesa R, Miller CB, Thyne M, Mangan J, Goldberger S, Fazal S, et al. Impact of myeloproliferative neoplasms (MPNs) on patients’ overall health and productivity: results from the MPN LANDMARK SURVEY in the United States. Blood. 2014;124(21):3183.

    Google Scholar 

  35. Scherber RM, Knapper S, Fox S, Kosiorek HE, Shah M, Abdi-Moradi S, et al. Assessment and validation of the EQ-5D among a population of myeloproliferative neoplasm patients. Blood. 2015;126:5179.

    Google Scholar 

  36. • Gowin K, Eckert R, Huberty J, Gowin KL, Ginos B, Kosiorek HE, et al. Impact of weight on symptom burden outcomes in myeloproliferative neoplasm patients participating in an online yoga intervention. Blood. 2016;128:5481. This was the first dedicated non-pharmacological intervention for MF symptom management.

  37. Scherber RM, Senyak Z, Kosiorek HE, Dueck AC, Clark MM, Boxer M, et al. Treating depression in the myeloproliferative neoplasms: the role and implications of poorly controlled symptoms and psychosocial factors. Blood. 2016;128:5474.

    Google Scholar 

  38. Mesa RA, Li CY, Schroeder G, Tefferi A. Clinical correlates of splenic histopathology and splenic karyotype in myelofibrosis with myeloid metaplasia. Blood. 2001;97(11):3665–7.

    Article  CAS  PubMed  Google Scholar 

  39. Geyer HL, Scherber R, Dueck A, Kiladjian J, Xiao Z, Slot S, et al. Impact of splenomegaly on myelofibrosis symptoms and association with clinical features: an analysis by the MPN Quality of Life International Study Group. European Hematology Association Annual Meeting Abstracts (E1339). 2016.

Download references

Author information

Authors and Affiliations

  1. Division of Hospital Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA

    Holly Geyer

  2. Division of Hematology and Medical Oncology, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA

    Ruben A. Mesa

Authors
  1. Holly Geyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruben A. Mesa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruben A. Mesa.

Ethics declarations

Conflict of Interest

Holly Geyer declares no potential conflicts of interest.

Ruben A. Mesa reports consulting fees from Novartis, Ariad, and Galena, and research support from Incyte, Gilead, CTI, Promedior, and Celgene.

Human and Animal Rights and Informed Consent

This article contains no studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Myeloproliferative Neoplasms

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geyer, H., Mesa, R.A. Approach to MPN Symptom Assessment. Curr Hematol Malig Rep 12, 381–388 (2017). https://doi.org/10.1007/s11899-017-0399-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-017-0399-5

Keywords

Search

Navigation