The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: An international study of 797 patients

P. Guglielmelli, T. L. Lasho, G. Rotunno, J. Score, C. Mannarelli, A. Pancrazzi, F. Biamonte, A. Pardanani, K. Zoi, A. Reiter, A. Duncombe, T. Fanelli, D. Pietra, E. Rumi, C. Finke, N. Gangat, R. P. Ketterling, R. A. Knudson, C. A. Hanson, A. BosiA. Pereira, R. Manfredini, F. Cervantes, G. Barosi, M. Cazzola, N. C P Cross, A. M. Vannucchi, A. Tefferi

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Abstract

We recently defined a high-molecular risk category (HMR) in primary myelofibrosis (PMF), based on the presence of at least one of the five 'prognostically detrimental' mutated genes (ASXL1, EZH2, SRSF2 and IDH1/2). Herein, we evaluate the additional prognostic value of the 'number' of mutated genes. A total of 797 patients were recruited from Europe (n=537) and the Mayo Clinic (n=260). In the European cohort, 167 (31%) patients were HMR: 127 (23.6%) had one and 40 (7.4%) had two or more mutated genes. The presence of two or more mutations predicted the worst survival: median 2.6 years (hazard ratio (HR) 3.8, 95% confidence interval (CI) 2.6-5.7) vs 7.0 years (HR 1.9, 95% CI 1.4-2.6) for one mutation vs 12.3 years for no mutations. The results were validated in the Mayo cohort and prognostic significance in both cohorts was independent of International Prognostic Scoring System (IPSS; HR 2.4, 95% CI 1.6-3.6) and dynamic IPSS (DIPSS)-plus (HR 1.9, 95% CI 1.2-3.1), respectively. Two or more mutations were also associated with shortened leukemia-free survival (HR 6.2, 95% CI 3.5-10.7), also Mayo validated. Calreticulin mutations favorably affected survival, independently of both number of mutations and IPSS/DIPSS-plus. We conclude that the 'number' of prognostically detrimental mutations provides added value in the combined molecular and clinical prognostication of PMF.

Original languageEnglish
Pages (from-to)1804-1810
Number of pages7
JournalLeukemia
Volume28
Issue number9
DOIs
Publication statusPublished - 2014

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Primary Myelofibrosis
Mutation
Confidence Intervals
Survival
Calreticulin
Genes
Leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Guglielmelli, P., Lasho, T. L., Rotunno, G., Score, J., Mannarelli, C., Pancrazzi, A., ... Tefferi, A. (2014). The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: An international study of 797 patients. Leukemia, 28(9), 1804-1810. https://doi.org/10.1038/leu.2014.76

The number of prognostically detrimental mutations and prognosis in primary myelofibrosis : An international study of 797 patients. / Guglielmelli, P.; Lasho, T. L.; Rotunno, G.; Score, J.; Mannarelli, C.; Pancrazzi, A.; Biamonte, F.; Pardanani, A.; Zoi, K.; Reiter, A.; Duncombe, A.; Fanelli, T.; Pietra, D.; Rumi, E.; Finke, C.; Gangat, N.; Ketterling, R. P.; Knudson, R. A.; Hanson, C. A.; Bosi, A.; Pereira, A.; Manfredini, R.; Cervantes, F.; Barosi, G.; Cazzola, M.; Cross, N. C P; Vannucchi, A. M.; Tefferi, A.

In: Leukemia, Vol. 28, No. 9, 2014, p. 1804-1810.

Research output: Contribution to journalArticle

Guglielmelli, P, Lasho, TL, Rotunno, G, Score, J, Mannarelli, C, Pancrazzi, A, Biamonte, F, Pardanani, A, Zoi, K, Reiter, A, Duncombe, A, Fanelli, T, Pietra, D, Rumi, E, Finke, C, Gangat, N, Ketterling, RP, Knudson, RA, Hanson, CA, Bosi, A, Pereira, A, Manfredini, R, Cervantes, F, Barosi, G, Cazzola, M, Cross, NCP, Vannucchi, AM & Tefferi, A 2014, 'The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: An international study of 797 patients', Leukemia, vol. 28, no. 9, pp. 1804-1810. https://doi.org/10.1038/leu.2014.76
Guglielmelli, P. ; Lasho, T. L. ; Rotunno, G. ; Score, J. ; Mannarelli, C. ; Pancrazzi, A. ; Biamonte, F. ; Pardanani, A. ; Zoi, K. ; Reiter, A. ; Duncombe, A. ; Fanelli, T. ; Pietra, D. ; Rumi, E. ; Finke, C. ; Gangat, N. ; Ketterling, R. P. ; Knudson, R. A. ; Hanson, C. A. ; Bosi, A. ; Pereira, A. ; Manfredini, R. ; Cervantes, F. ; Barosi, G. ; Cazzola, M. ; Cross, N. C P ; Vannucchi, A. M. ; Tefferi, A. / The number of prognostically detrimental mutations and prognosis in primary myelofibrosis : An international study of 797 patients. In: Leukemia. 2014 ; Vol. 28, No. 9. pp. 1804-1810.
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abstract = "We recently defined a high-molecular risk category (HMR) in primary myelofibrosis (PMF), based on the presence of at least one of the five 'prognostically detrimental' mutated genes (ASXL1, EZH2, SRSF2 and IDH1/2). Herein, we evaluate the additional prognostic value of the 'number' of mutated genes. A total of 797 patients were recruited from Europe (n=537) and the Mayo Clinic (n=260). In the European cohort, 167 (31{\%}) patients were HMR: 127 (23.6{\%}) had one and 40 (7.4{\%}) had two or more mutated genes. The presence of two or more mutations predicted the worst survival: median 2.6 years (hazard ratio (HR) 3.8, 95{\%} confidence interval (CI) 2.6-5.7) vs 7.0 years (HR 1.9, 95{\%} CI 1.4-2.6) for one mutation vs 12.3 years for no mutations. The results were validated in the Mayo cohort and prognostic significance in both cohorts was independent of International Prognostic Scoring System (IPSS; HR 2.4, 95{\%} CI 1.6-3.6) and dynamic IPSS (DIPSS)-plus (HR 1.9, 95{\%} CI 1.2-3.1), respectively. Two or more mutations were also associated with shortened leukemia-free survival (HR 6.2, 95{\%} CI 3.5-10.7), also Mayo validated. Calreticulin mutations favorably affected survival, independently of both number of mutations and IPSS/DIPSS-plus. We conclude that the 'number' of prognostically detrimental mutations provides added value in the combined molecular and clinical prognostication of PMF.",
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T2 - An international study of 797 patients

AU - Guglielmelli, P.

AU - Lasho, T. L.

AU - Rotunno, G.

AU - Score, J.

AU - Mannarelli, C.

AU - Pancrazzi, A.

AU - Biamonte, F.

AU - Pardanani, A.

AU - Zoi, K.

AU - Reiter, A.

AU - Duncombe, A.

AU - Fanelli, T.

AU - Pietra, D.

AU - Rumi, E.

AU - Finke, C.

AU - Gangat, N.

AU - Ketterling, R. P.

AU - Knudson, R. A.

AU - Hanson, C. A.

AU - Bosi, A.

AU - Pereira, A.

AU - Manfredini, R.

AU - Cervantes, F.

AU - Barosi, G.

AU - Cazzola, M.

AU - Cross, N. C P

AU - Vannucchi, A. M.

AU - Tefferi, A.

PY - 2014

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