Long term follow up of 93 families with myeloproliferative neoplasms: life expectancy and implications of JAK2V617F in the occurrence of complications

The long-term evolution of familial myeloproliferative neoplasms was studied in 93 families with 227 subjects including 97 with polycythemia vera (PV), 105 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF) and 11 chronic myeloid leukemia (CML). In PV patients, with 12 years of median follow-up, overall survival was 83% at 10 years and 37% at 20 years. A high JAK2V617F allele burden was correlated with the transformation to myelofibrosis (p < 0.0001), but not with the transformation to acute leukemia. Among the 105 ET, with 8 years of median follow-up, overall survival was 83% at 10 years and 57% at 20 years. Progression to acute leukemia and progression to myelofibrosis were 10% and 13%. There was a trend toward a more frequent evolution to myelofibrosis when the JAK2V617F mutated allele burden was > 50% (p = 0.09), but not to AML. Hematologic transformation of the MPN was responsible for 69% of the deaths, cerebral stroke for 7% and 4% died of myocardial infarction. Eleven JAK2V617F mutated patients developed 13 deep splanchnic thromboses in PV and ET. Finally whereas patients with familial PV and ET have a comparable prognosis to non‐familial MPN, the JAK2V617F mutation was associated with a more frequent occurrence of thrombosis in the entire population.