Areas of uncertainty and perspectives regarding the treatment of patients with ET
| . | Perspectives . |
|---|---|
| Areas of uncertainty in the management of ET | • Triple-negative patients. These cases may include patients with ET associated with noncanonical mutations of MPL, subjects with hereditary thrombocytosis attributable to germ line mutations of JAK2, MPL, or THPO, and individuals with nonclonal disorders. Although these patients generally have a favorable outcome, the above conditions differ substantially: clinical decision-making is therefore challenging. • Relevance of leukocytosis for clinical decision-making. ET patients may have 1 or more features of prefibrotic myelofibrosis (see minor criteria in Table 3: anemia, leukocytosis, palpable splenomegaly, and increased lactate dehydrogenase level) without fulfilling the 2016 WHO diagnostic criteria for this latter condition. These features may suggest a more advanced disease, presumably a transition to myelofibrosis. Leukocytosis has been found to be an independent predictor of poor clinical outcome, in terms of both thrombosis risk and reduced survival.3,47,49,50 It is currently unclear how this information should be used in clinical decision-making. • Low-dose aspirin in low-risk patients with CALR-mutant ET. A recent retrospective study has shown that in patients with low-risk CALR-mutant ET, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding.42 This observation suggests a genotype-based approach to antiplatelet therapy in low-risk patients, and observation alone appears a reasonable option for those with CALR-mutant ET without concomitant cardiovascular risk factors and without microvascular symptoms. • Optimal treatment of low-risk patients with JAK2-mutant ET and concomitant cardiovascular risk factors. According to current recommendations, these patients are treated with low-dose aspirin. However, more aggressive treatments have been suggested, including twice-daily aspirin41 and the use of a cytoreductive drug.42 |
| Potential disease-modifying drugs for treatment of ET | • Pegylated interferon α-2a is currently evaluated in the clinical trial entitled “Randomized trial of pegylated interferon alfa-2a vs hydroxyurea in PV and ET” (ClinicalTrials.gov Identifier: NCT01259856). • Ropeginterferon α-2 has been shown to induce hematologic and molecular responses with low toxicity in patients with PV.88 • Ruxolitinib was found to be effective in patients with ET who were refractory or intolerant to hydroxyurea, inducing complete molecular responses in some cases.84,85 |
| . | Perspectives . |
|---|---|
| Areas of uncertainty in the management of ET | • Triple-negative patients. These cases may include patients with ET associated with noncanonical mutations of MPL, subjects with hereditary thrombocytosis attributable to germ line mutations of JAK2, MPL, or THPO, and individuals with nonclonal disorders. Although these patients generally have a favorable outcome, the above conditions differ substantially: clinical decision-making is therefore challenging. • Relevance of leukocytosis for clinical decision-making. ET patients may have 1 or more features of prefibrotic myelofibrosis (see minor criteria in Table 3: anemia, leukocytosis, palpable splenomegaly, and increased lactate dehydrogenase level) without fulfilling the 2016 WHO diagnostic criteria for this latter condition. These features may suggest a more advanced disease, presumably a transition to myelofibrosis. Leukocytosis has been found to be an independent predictor of poor clinical outcome, in terms of both thrombosis risk and reduced survival.3,47,49,50 It is currently unclear how this information should be used in clinical decision-making. • Low-dose aspirin in low-risk patients with CALR-mutant ET. A recent retrospective study has shown that in patients with low-risk CALR-mutant ET, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding.42 This observation suggests a genotype-based approach to antiplatelet therapy in low-risk patients, and observation alone appears a reasonable option for those with CALR-mutant ET without concomitant cardiovascular risk factors and without microvascular symptoms. • Optimal treatment of low-risk patients with JAK2-mutant ET and concomitant cardiovascular risk factors. According to current recommendations, these patients are treated with low-dose aspirin. However, more aggressive treatments have been suggested, including twice-daily aspirin41 and the use of a cytoreductive drug.42 |
| Potential disease-modifying drugs for treatment of ET | • Pegylated interferon α-2a is currently evaluated in the clinical trial entitled “Randomized trial of pegylated interferon alfa-2a vs hydroxyurea in PV and ET” (ClinicalTrials.gov Identifier: NCT01259856). • Ropeginterferon α-2 has been shown to induce hematologic and molecular responses with low toxicity in patients with PV.88 • Ruxolitinib was found to be effective in patients with ET who were refractory or intolerant to hydroxyurea, inducing complete molecular responses in some cases.84,85 |