Essential Thrombocythemia in Young Individuals: Frequency and Risk Factors for Vascular Events and Evolution to Myelofibrosis in 126 Patients.

Abstract

Vascular events and evolution to either myelofibrosis (MF) and acute leukemia (AL) are the main causes of morbidity and mortality in individuals with essential thrombocythemia (ET). However, the frequency of these complications in young ET patients is not well known. The objective of the present study was to assess the frequency of vascular events and the incidence of MF and AL in young patients with ET and to identify the factors associated with the development of such complications. In 126 subjects diagnosed with ET at a median age of 31 years (range: 5–40), overall survival and probability of survival free of either thrombosis, bleeding, MF, AL, and polycythemia vera (PV) were analyzed by the Kaplan-Meier method, followed by the log-rank test. With a median follow-up of eleven years (range: 4–25) three patients have died, being the probability of survival 98% at ten years. A total of 31 thrombotic events were registered in 25 patients; thrombosis-free survival (TFS) was 84% at ten years. Tobacco use was the only factor associated with an increased thrombotic risk, since TFS at 10 years was 72% in smokers versus 90% in non-smokers (p=0.03). Severe hemorrhagic complications were observed in 11 patients, and the estimated probability of bleeding-free survival was 92% at ten years. Evolution to MF was seen in 6 patients, four of whom had never received treatment for ET. MF-free survival was 97% at 10 years, with the risk being higher in patients showing an increased reticulin network in the bone marrow biopsy performed at diagnosis of ET (p=0.005). Transformation to AL was registered in one patient. JAK2 was mutated in 33 out of the 87 assessable patients (38%) and the mutation was associated with higher Hb values at diagnosis (p = 0.001). ET evolved into PV in five patients, being the probability of evolution into PV of 15% in JAK2 V617F positive patients versus 0% in JAK2 V617F negative patients (p=0.01). In conclusion, severe vascular complications are not infrequent in young subjects with ET, whereas transformation to MF or AL is a rare event.

The JAK2V617F mutation and thrombosis

“…In Vannucchi et al (2007a), the independent association was only with rare homozygous‐mutant cases, in Kittur et al (2007) the association was lost if prior thrombosis was incorporated into the model, and in Heller et al (2006), the majority of the thrombotic events occurred prior to or at diagnosis. Four studies refuted the association between JAK2 V617F mutation status and thrombotic risk (Wolanskyj et al , 2005; Tefferi et al , 2006; Alvarez‐Larran et al , 2007; Carobbio et al , 2007), though these tended to include fewer patients, and analysed arterial and venous events together. Consequently, they may not have detected small differences in rates of vascular events between the V617F‐positive and the V617F‐negative groups, particularly differences confined to either arterial or venous subtypes.…”

The prognostic relevance of serum lactate dehydrogenase and mild bone marrow reticulin fibrosis in essential thrombocythemia

“…It is, therefore, important to consider the current findings as being preliminary and in need of validation by additional studies that are designed to offset potential test limitations. Future studies should also include adequate numbers of informative cases with leukemic and fibrotic progressions, as well as thrombotic events, in order to assess LDH impact on such events, in the context of previously identified risk factors for thrombosis (advanced age, presence of JAK2 V617F and MPL , and history of thrombosis), leukemic transformation (thrombosis history, platelets >1 million/μL, leukocytosis, age >60 years) and fibrotic progression (anemia, age >60 years, male sex, increased BM reticulin fibrosis, presence of MPL mutation, and elevated serum LDH) …”

The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera

“…Survival of patients in the different MPN entities has been reported in several cohort studies; the majority of reports have shown a significantly shorter survival of patients with PV compared to the normal population (8, 13, 31, 32). On the other hand, several retrospective studies of groups of patients with ET have proved no or little effect on life expectancy compared with the normal population (8, 33–35). Our cohort of 280 patients diagnosed with PV or ET, with the use of the PVSG criteria, in the city of Gothenburg, Sweden, studied between 1983 and 1999 confirm these observed differences in survival expectancy.…”