Criteria of response and definition of resistance and intolerance to hydroxyurea (HU) in polycythemia vera (PV) were proposed by the European LeukemiaNet (ELN). Such criteria were evaluated in 261 PV patients (median follow-up, 7.2 years) treated with HU for a median of 4.4 years. Complete response, partial response, and no response were observed in 24%, 66%, and 10% of patients, respectively. Achieving ELN response (complete or partial) or hematocrit response did not result in better survival or less thrombosis and bleeding. On the contrary, having no response in leukocyte count was associated with higher risk of death (HR, 2.7; 95% confidence interval [CI], 1.3%-5.4%; P ‫؍‬ .007), whereas lack of response in platelet count involved a higher risk of thrombosis and bleeding. Resistance and intolerance to HU was registered in 11% and 13% of patients, respectively. Resistance to HU was associated with higher risk of death (HR, 5.6; 95% CI, 2.7%-11.9%; P < .001) and transformation (HR, 6.8; 95% CI, 3.0%-15.4%; P < .001). In summary, fulfilling the ELN definition for response to HU was not associated with a benefit in the clinical outcome in PV, whereas response in platelet and white blood cell counts were predictive of less thrombohemorrhagic complications and better prognosis, respectively. Resistance to HU was an adverse prognostic factor. (Blood. 2012;119(6):1363-1369)

We conducted a large international nested case-control study including 1,881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n=647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer and melanoma) and controls (n=1,234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR=1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had twofold higher risk of non-melanoma (NM) skin cancer (OR=2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR=3.74, 95% CI 1.00-14.01), ruxolitinib (OR=3.87, 95% CI 1.18-12.75) and for drug combination (OR=3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors (p = 0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.

Summary Standardized criteria of response to treatment and a unified definition of resistance/intolerance to hydroxycarbamide (HC) in essential thrombocythaemia (ET) have been proposed by the European LeukaemiaNet (ELN). We have retrospectively evaluated such criteria in 166 ET patients treated with HC for a median of 4·5 years. Overall, 134 patients achieved a complete clinicohaematological response (CR) and 25 a partial response. Thirty‐three patients met at least one of the ELN criteria defining resistance (n = 15) or intolerance (n = 21) to HC. Fifteen cases developed anaemia with thrombocytosis, which was associated with a high incidence of myelofibrosis and death from any cause. Other definitions of resistance were less useful. Factors determining the thrombotic risk were a history of prior thrombosis and a baseline leucocyte count >10 × 109/l. Of note, patients achieving a CR, even if sustained during the entire follow‐up, did not benefit from a lower incidence of thrombosis or an improved survival. In conclusion, most ET patients respond to HC, but the achievement of response, as defined by the ELN, does not correlate with the patients’ outcome. The best discriminating ELN criterion of resistance to HC was the detection of anaemia, which also identified a subgroup of patients with poor prognosis.

No abstract