Myelofibrosis (MF) is a Ph-negative myeloproliferative neoplasm, classified as Primitive (PMF) or secondary to Polycythemia Vera (PPV-MF) or to Essential Thrombocythemia (PET-MF). Treatments for MF include hydroxycarbamide (HU) and JAK-inhibitors.
PMF has a better overall survival than secondary MF, but data from literature are not sufficient to predict whether age, molecular biology and therapy may affect overall survival or incidence of post-diagnosis complications in these different subsets of patients.
Retrospectively analyse a cohort of World Health Organization-defined MF patients, diagnosed from 1988 to 2015 by a single Italian haematological centre (Turin), and observe possible differences on overall survival and post-diagnosis infective, thrombotic or hemorrhagic complications based on age, therapy and molecular biology. Overall survival (OS) was estimated from diagnosis to death for any cause using Kaplan Meyer method and Hazard Ratio (HR) were estimated with the Cox Model. Dichotomous outcomes (post-diagnosis infective, thrombotic, hemorrhagic complications) were compared between groups using chi-squared test.
We analysed123 MF patients: 58 (47%) primary MF and 65 (53%) secondary MF (28 PPV-MF and 37 PET-MF). Shared by age, patients were assessed into three groups: under 60 years (40 pts, 33%), between 60-69 years (28 pts, 23%) and over 70 years (55 pts, 44%) Median follow-up was 40 months.
Sixty-eight (55%) patients were positive for JAK2-mutation, 14 (11%) for CALR-mutation and 4 (3,2%) for MPL-mutation whereas 15 (12%) patients were triple-negative. Ninety-nine (80,5%) patients received a therapy with HU or JAK-inhibitors, while 24 patients (19,5%) did not receive any cytoreductive therapy.
At a median follow-up of 36 months, OS rates were significantly different according to age cohorts: 100% in patients under 60 years, 96% in those between 60-69 years and 78% in patients over 70 years (p=0.001).
36-months OS was also significantly different between PMF and secondary MF: 96% (95% IC: 84-98) versus 86% (95% IC: 85-99) (p=0.01) (HR=0.35). Impact on OS seems to be stronger, even though not significant, in patients under 60 years than in those over 60 years [<60ys HR=0.16; >60ys HR=0.61 (p=0.363)]
Shared patients by age (under 60ys, over 60ys), no significant difference was found in the rate of: infective post-diagnosis complications (34% vs 42%, p=0,792); thrombotic events (19% vs 21%, p=0,425) or hemorrhagic events (22 % vs 19%, p=0,855).
Post-diagnosis infections, thrombotic or hemorrhagic complications were present in 38%, 15% and 22%, respectively in patients on treatment whereas in 42%, 8% and 12%, respectively in treatment-naïve patients. Therapy did not impact on age nor on primary or secondary nature of MF.
The rate of post-diagnosis complications (infective, thrombotic or hemorrhagic) was similar among age cohorts: 51 % in under 60 year-old patients, 50% in 60-69 and 58% in over 70 patients (p=0,741); moreover post-diagnosis complications were observed in 50% of patients who did not receive treatment and in 55% of those on treatment (p=0,689).
At last significant connections between JAK2/CALR/MPL positivity and different cohorts of age were not been observed.
In patients with MF, our study showed a significant impact of age over 60ys on OS. We confirmed that PMF has a better survival than secondary MF, independently from age, even if the differences seem to be more important in under 60ys group. Moreover we observe a not significant difference between the therapy effect and molecular profile in PMF or secondary MF.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.