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.

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.

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, Rossella; Cervantes, F.; Barosi, G.; Cazzola, M.; Cross, N. C. P.; Vannucchi, A. M.; Tefferi, A.. - In: LEUKEMIA. - ISSN 0887-6924. - STAMPA. - 28:(2014), pp. 1804-1810. [10.1038/leu.2014.76]

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

MANFREDINI, Rossella;
2014

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.
2014
28
1804
1810
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, Rossella; Cervantes, F.; Barosi, G.; Cazzola, M.; Cross, N. C. P.; Vannucchi, A. M.; Tefferi, A.. - In: LEUKEMIA. - ISSN 0887-6924. - STAMPA. - 28:(2014), pp. 1804-1810. [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, Rossella; Cervantes, F.; Barosi, G.; Cazzola, M.; Cross, N. C. P.; Vannucchi, A. M.; Tefferi, A.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1074843
Citazioni
  • ???jsp.display-item.citation.pmc??? 110
  • Scopus 236
  • ???jsp.display-item.citation.isi??? 214
social impact