Mortality rates for younger adults with myeloproliferative neoplasms (MPNs) were similar to historical controls of older patients with these diseases, according to results of a retrospective study published in the European Journal of Haematology.
Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), are most frequently diagnosed in late middle or early old age, with the median age at diagnosis ranging from 56 years for ET to 70 years for PMF. Unlike some acute hematologic malignancies that exhibit a bimodal age distribution, myeloproliferative neoplasms are not frequently diagnosed in younger patients. Hence, information on the demographic and clinical characteristics of younger patients with these diagnoses, as well as the natural history of these diseases in this age group, is limited.
In this study, 109 adult patients ages 18 to 45 were identified in the patient medical records of 4 medical centers in Israel. Of these patients, 50% were found to have ET; 34%, PV; 14%, PMF; and 3% an unspecified myeloproliferative neoplasm. Of the patients with PMF, approximately three-quarters had overt PMF and the remainder were found to have prefibrotic myelofibrosis. The median follow-up time was 8 years.
Compared with the ET or PMF subgroups, in which the median age at diagnosis was 31 years, median age at diagnosis of PV was 38 years (P =.003). Although no significant differences were noted in platelet or leukocyte counts between the 3 subgroups, higher median hemoglobin levels (P <.001) and hematocrits (P <.001) at diagnosis also distinguished patients with PV from those in the other 2 subgroups. Other notable differences were larger spleens (P <.001) and higher blasts counts (P =.009) in patients with PMF compared with those in the PV or ET subgroups.
A key finding was that 37% of patients in the study cohort experienced 1 or more thrombotic events. Most of these were venous thrombotic events, with less than one-quarter of patients experiencing an arterial thrombotic event. Interestingly, more than three-quarters of venous thrombotic events occurred in the splanchnic vein, an uncommon occurrence in the general population. On multivariate analysis, only spleen size more than 12 cm was significantly associated with thrombosis (hazard ratio [HR], 5.6, CI, 1.4‐22).
Regarding the low number of arterial thrombotic events observed in this study compared with previous studies of myeloproliferative neoplasms in all age groups where arterial events were more common than venous events, the authors commented that “this is probably because of lower rates of arterial vascular risk factors such as hypertension, hyperlipidemia, or diabetes in the younger age population.”
With respect to the high rate of venous thrombotic events in the splanchnic vein in this younger cohort, the study authors noted that the longer disease course in younger patients increases their risk of developing thrombotic complications during their lifetime.
Of the 11% of patients with PV or ET who developed secondary myelofibrosis, the median time from diagnosis to myelofibrosis was 7.9 years, and the 10-year risk for secondary myelofibrosis was similar in these 2 subgroups (0.13 [ET] vs 0.19 [PV], P = 0.51).
Two patients with PMF developed secondary acute myeloid leukemia. Of the 6 patients who died during the follow-up period, 5 had an initial diagnosis of PMF or developed secondary myelofibrosis, and none died from complications due to a thrombotic event. The 10-year risk of disease transformation to acute myeloid leukemia or death was 0.3 in patients with an initial diagnosis of PMF.
The authors identified several study limitations, including the retrospective design and the absence of an older cohort comparator group.
The risks of mortality and disease progression for young adults with myeloproliferative neoplasms are quite similar to those for the older population; however, they demonstrate unique thrombotic features. “Thrombosis is a frequent presenting sign and is most commonly venous, with an exceedingly high incidence of splanchnic sites,” the study authors reported.
Barzilai M, Kirgner I, Avivi I, et al. Characteristics and outcomes of young adults with Philadelphia-negative myeloproliferative neoplasms [published online April 2, 2019]. Eur J Haematol. doi: 10.1111/ejh.13232