Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders

Abstract

Among the 'classic' BCR/ABL-negative chronic myeloproliferative disorders, primary myelofibrosis (PMF) is associated with a substantial life-expectancy reduction. In this disease, initial haemoglobin level is the most important prognostic factor, whereas age, constitutional symptoms, low or high leukocyte counts, blood blast cells and cytogenetic abnormalities are also of value. Several prognostic systems have been proposed to identify subgroups of patients with a different risk, which is especially important in younger individuals, who may benefit from therapies with curative potential. Essential thrombocythaemia (ET) affects the patients' quality of life more than the survival, due to the high occurrence of thrombosis, whereas polycythaemia vera (PV) has a substantial morbidity derived from thrombosis but also a certain reduction in life expectancy. Therefore, in the latter disorders, prognostic studies have focused primarily on prediction of the thrombosis, with age and a previous history of thrombosis being the main prognostic factors of such complication. The importance of higher leukocyte counts in thrombosis development has been recently pointed out in ET and PV, where a role for mutated JAK2 allele burden has also been noted. With regard to PMF, the possible association of the mutation with shorter survival and higher acute transformation rate is currently being evaluated

A retrospective study on 226 polycythemia vera patients: impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and non-alkylating drugs

“…This certainly contributed to the high proportion (70%) of patients in the group of high thrombotic risk. In spite of these unfavorable prognostic features, the overall survival (91% at the median follow-up time of 5.84 years) compares favorably to that reported in many other studies [3][4][5][6]. Although we did not perform a prospective, randomized study and the median follow-up is shorter than 10 years, the wide use in our patients of lowdose ASA and the strong limitation of alkylating cytotoxic therapy may have contributed to this more favorable outcome and to an incidence of leukemic transformation in the lowest range of values reported in literature [4,[6][7][8].…”

“…Polycythemia vera (PV) is the most common chronic myeloproliferative neoplasm, with an annual incidence of 2.3 per 100,000 [1,2], a reported median survival of 10-15 years [3][4][5][6] and an overall mortality of 3.5 per 100 person/year [5]. Thrombotic complications are the main cause of morbidity and mortality, occurring in more than one third of patients and causing 35-45% of deaths [5,6].…”

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…This difference may be due to a longer observation time (median follow-up: 6.6 years, total of 5,650 person years) and very important, early diagnosis was facilitated by strictly performing a BM biopsy at onset of a suspected MPN with presentation of relevant clinical features. Comparable with advanced stage PMF [22,102,128,[130][131][132][133][134][135][136][138][139][140][141], degree of anemia (initial hemoglobin level), age at diagnosis, presence of peripheral blasts and platelet as well as leukocyte counts were of significant predictive value [102,128,135,138]. These results are in keeping with the assumption that in prodromal PMF according to multivariate risk analysis features indicating expansion of disease with involvement of extramedullary organs or myeloid metaplasia exerts the most important impact on prognosis [102,128,135].…”

“…Altogether a stepwise, however, unpredictable evolution of the disease process in PMF associated with correspondingly expressed clinical data has to be realized [111,114]. An extreme heterogeneity of survival patterns has been reported in larger series of patients with PMF ranging between 3.5 and 10 years [22,102,128,[130][131][132][133][134][135][136][137][138][139][140][141]. However, only a few of these studies considered the full spectrum of disease manifestation including prodromal stages [108,128,135,138].…”

Kinase drug discovery approaches in chronic myeloproliferative disorders

“…Ph(À) MPDs are characterized by a long clinical course and marrow hypercellularity. One of the unique features of MPDs is that the median survival of MPD patients is relatively high (Cervantes et al, 2008). However, quality of life in MPD patients is adversely affected by a spectrum of complications including thrombosis, hemorrhage, microvascular symptoms, pruritus, hepatomegaly, anemia, cachexia, metabolic abnormalities and severe constitutional symptoms (Campbell and Green, 2005;Mesa et al, 2006a, b).…”