A Dynamic Prognostic Model To Predict Survival in Post-Polycythemia Vera Myelofibrosis.

Abstract

Polycythemia vera (PV) is a chronic myeloproliferative disorder with a propensity to develop myelofibrosis, a condition named post polycythemia vera myelofibrosis (post-PV MF). Survival and prognostic factors after transition to MF remain to be defined. We studied 68 patients with post-PV MF to define survival and prognostic factors for survival at diagnosis of post-PV MF. We also developed a dynamic prognostic model to predict survival at any time from diagnosis of post-PV MF. The median interval between the diagnosis of PV and that of post-PV MF was 13 years (range, 4–29.6 years). Patients with post-PV MF were observed for 181 person-years of follow-up. At diagnosis of post-PV MF, 43 (63%) of 68 patients had less than 65 years. During the follow-up, the incidence of thrombosis was 42 × 1000 person-years (95% CI: 19–93.5) and the incidence of leukemia was 50.3 × 1000 person-years (95% CI: 26–115). The median survival was 5.7 years. Multivariable Cox proportional hazard regression including age, hemoglobin value, platelet count, leukocyte count, and spleen size, showed that hemoglobin < 10 g/dL (P < .001) and platelet count < 100 × 109/L (P= .026) were independent risk factors for survival. We stratified patients at diagnosis of post-PV MF, according to these factors, obtaining two risk groups with significantly different survival (P = .003): low risk (Hb > 10 g/dL and platelet count > 100 × 109/L) with a median survival of 7 years, and high risk (Hb < 10 g/dL or platelet count < 100 × 109/L) with a median survival of 2 years. The prognostic model retained significance after adjustment for age in a multivariable Cox proportional hazard regression (HR: 4.3, 95% CI: 1.6–11.4; P= .003). To assess whether this prognostic model may predict survival at any time from diagnosis of post-PV MF, we evaluated in a time-dependent analysis 64 patients who had longitudinal blood cell counts during follow-up. As first step, we evaluated univariate survival analysis with hemoglobin value < 10 g/dL and platelet count < 100 ×109/L as time-dependent covariates. Both time-dependent parameters affected survival (HR for hemoglobin 5.8, 95% CI: 2.2–15.2, P < 0.001; HR for platelets 4.5, 95% CI: 1.67-12, P=.002). As second step, we evaluated the prognostic model assessed at diagnosis as time-dependent covariate, to define whether the acquisition of one risk factor during follow-up may affect survival. The HR was 7.5 (95% CI: 2.4-23.4; P < .001). The time-dependent prognostic model retained statistical significance after adjustment for age (P < .001). In conclusion, in patients developing post-PV myelofibrosis, a prognostic model based on hemoglobin level < 10 g/dL and platelet count < 100 × 109/L may predict survival at diagnosis of post-PV MF and at any time thereafter.

Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2‐mutated polycythemia vera

“…It has been reported that approximately 10.5% of patients with PV develop post‐PV MF , and the 10‐year and 20‐year cumulative incidence of post‐PV MF is 5.0–15% and 21–32%, respectively . Bonicelli et al showed that 11.5% of patients developed post‐PV MF after a median of 116 months from the diagnosis of PV, with a 10‐year, 15‐year, and 20‐year cumulative risk of 6.0%, 14%, and 26%, respectively .…”

“…Polycythemia vera (PV) is a chronic progressive myeloproliferative neoplasm (MPN) characterized by pancytosis, especially the overproduction of red blood cells (RBCs), and therefore often associated with thrombocytosis and leukocytosis. It is estimated that PV will evolve into life‐threatening myelofibrosis (post‐PV MF) in up to 20% of patients . Passamonti et al reported that leukocytosis at diagnosis of PV was a risk factor for the progression of PV to post‐PV MF .…”

“…It is estimated that PV will evolve into life‐threatening myelofibrosis (post‐PV MF) in up to 20% of patients . Passamonti et al reported that leukocytosis at diagnosis of PV was a risk factor for the progression of PV to post‐PV MF . However, the risk factors remain unclear in Chinese patients with PV.…”

“…The survival of PV patients declines considerably after evolution to post‐PV MF, and the reported median survival of patients with post‐PV MF varies widely . Unfortunately, no generally accepted predictive model is currently available to stratify the risk factors in patients with post‐PV MF, and treatment decisions are primarily based on the International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) for primary MF (PMF) .…”

“…Unfortunately, no generally accepted predictive model is currently available to stratify the risk factors in patients with post‐PV MF, and treatment decisions are primarily based on the International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) for primary MF (PMF) . Passamonti et al developed a dynamic prognostic model to predict the survival of patients with PV who developed post‐PV MF based on hemoglobin level, platelet count, and leukocyte count, which was useful for predicting the progression of PV to post‐PV MF . This model has been recently updated based on age >65 years, time to secondary MF >15 years, previous thrombosis, constitutional symptoms, hemoglobin <10 g/dL, and circulating blast ≥1% .…”