Primary Myelofibrosis in Younger Patients: A Retrospective Analysis of the Gruppo Laziale MPN Ph-Negative

Primary myelofibrosis (PMF) is a rare disorder commonly diagnosed in the 6^th-7^th decade of life. In this retrospective study, we analyzed the clinical features at presentation of patients aged <50 years with a WHO-based diagnosis of primary PMF and compared them with those of the older cohort.

Fifty-seven patients aged <50 years (median age 44.9, range 29-49.5) were included in the study from an overall cohort of 581 patients (median age 72.1, range 50.5-90.1). The incidence of <50 year-old patients was 9.8%. In this younger cohort, 24 were males and 33 females, compared to 326 males and 198 females in the older cohort (M/F ratio 0.7 versus 1.6, p=0.01). A difference in hematologic parameters at presentation between the two cohorts was recorded with regard to the median hemoglobin level (13.6 gr/dl in younger vs 11.2 gr/dl in older patients, p=0.04) and median platelet count (566 x 10⁹/l in younger vs 340 x 10⁹/l in older patients, p=0.02). No differences were found in terms of WBC count (8.2 x 10⁹/l vs 9.6 x 10⁹/l, p=0.34). The IPSS risk score was int-2/high in only 7.0% of younger patients at presentation compared to 50.8% in older population. A mutational analysis was performed in 47 younger patients and in 314 older patients. The distribution of driver mutations was different according to age: JAK2 V617F mutations in 47.0% of younger patients vs 63.0% of older patients (p=0.01); CALR mutations in 12.0% of younger patients vs 9.4% of older patients (p=0.048). With regard to spleen enlargement at presentation, there were more patients without splenomegaly in the younger cohort (31.5% vs 25.0%) and less patients with a splenomegaly >5 cm (26.0% vs 35.0%) (p=0.03).

Eleven patients in the younger cohort (19.3%) referred a previous thrombotic event, which was primarily located in the splanchnic district (8/11 patients, 72.7%); in the older cohort, 72 patients presented a previous thrombotic event (13.7%), which was primarily located in the cerebral district (60.0%) with only 6/72 cases of splanchnic thrombosis (8.3%). Four younger patients (7.0%) developed PMI as a second neoplasia compared to 11 patients (2.1%) in the older cohort.

In summary, our data suggest that patients aged <50 years with a diagnosis of PMF presented with a more indolent disease at baseline, with a different mutational spectrum and a more frequent onset with splanchnic thromboses