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Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study. Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma. Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n = 8; essential thrombocythemia, n = 14; and primary myelofibrosis, n = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed (n = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy. Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma. [ABSTRACT FROM AUTHOR]

Since MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan. We enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL-mutated patients (n = 22; 3.8%) to JAK2V617F-mutated (n = 299; 51.6%), CALR-mutated (n = 144; 24.9%), and triple-negative (TN) (n = 114; 19.7%) patients. Thrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL-mutated group, which was the highest among all driver gene mutation groups (JAK2V617F-mutated, 8.7%; CALR-mutated, 3.5%; TN,1.8%). The MPL- and JAK2V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR-mutated (p = 0.043) and TN groups (p = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL-mutated patients (hazard ratio: 9.572, p = 0.032). MPL-mutated ET patients should require more intensive management to prevent recurrence of thrombosis. [ABSTRACT FROM AUTHOR]

Objectives: A proportion of patients with polycythemia vera (PV) and essential thrombocythemia (ET) harbor non‐driver mutations associated with poor prognosis. In this study, we analyzed the frequency of non‐driver mutations in a large Japanese PV and ET cohort. Furthermore, we studied the relationship of these mutations and prognosis in Japanese patients. Methods: We enrolled 843 Japanese patients with PV or ET. Non‐driver mutations were analyzed by target resequencing using next‐generation sequencing. The association of the mutations with the prognosis was estimated using multivariable logistic regression analysis and log‐rank test. Results: Non‐driver mutations were detected in 31.1% and 24.5% patients with PV and ET, respectively. Among them, ASXL1 mutations were identified as a risk factor for leukemic/myelofibrotic transformation in PV and ET patients (hazard ratio: 4.68, p =.006). The higher‐risk groups of the mutation‐enhanced international prognostic system (MIPSS)‐PV and MIPSS‐ET incorporating non‐driver mutations exhibited significantly shorter overall survival compared with the low‐risk group (p <.001). Conclusions: These results implicate the importance of studying non‐driver mutations for predicting the prognosis and survival of Japanese PV and ET patients. [ABSTRACT FROM AUTHOR]

Current guidelines for essential thrombocythemia (ET) patients recommend different treatment approaches based on thrombosis risk stratification models. However, these recommendations may not be applicable to some patients under real clinical settings. Therefore, we carried out a retrospective real-world validation study. Thrombosis-free survival (TFS) was compared between treatment naïve ET patients receiving different treatment approaches. ET patients were stratified by three representative risk models, the conventional, the International Prognostic Score for thrombosis in ET (IPSET-thrombosis), and revised IPSET-thrombosis. Treatment decisions were largely made by individual physicians, taking into account patient preferences and backgrounds. A total of 179 ET patients were included, and thrombotic events were observed in 26 patients. TFS was significantly longer in high-risk patients of all risk models receiving a combination of cytoreductive therapy (CRT) and antiplatelet therapy (APT) compared to CRT alone. Similar results were seen in intermediate-risk patients stratified by IPSET-thrombosis. In contrast, in very low- and low-risk patients of all risk models, TFS was not affected by addition of CRT, indicating that observation or APT alone is an appropriate treatment approach for these patients. We demonstrate that current guidelines provide optimal treatment approaches for Japanese ET patients under real-world clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Prefibrotic/early primary myelofibrosis (pre‐PMF) and essential thrombocythemia (ET) exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. In the WHO 2008 criteria, pre‐PMF was not defined as a subgroup of PMF; therefore, affected patients were at a higher risk of misdiagnosis with ET. In this study, we examined the prevalence of pre‐PMF patients among those previously diagnosed with ET in Japan. Method: We reviewed bone marrow specimens and clinical and molecular parameters of patients who were previously diagnosed with ET by the WHO 2008 criteria. Results: Among 107 ET patients, 13 patients were redefined as having pre‐PMF. Pre‐PMF patients exhibited a higher frequency of MPL mutation and increased platelet counts compared to true ET patients. Molecular analysis revealed the frequencies of high‐risk molecular mutations, such as ASXL1, EZH2, and SRSF2, were significantly increased in pre‐PMF patients than those in true ET patients. Conclusion: These results demonstrated the value of reexamining clinical records for patients diagnosed with ET by the WHO 2008 criteria and emphasized that adequate examinations of patients' bone marrow are crucial for an accurate diagnosis of pre‐PMF and ET. [ABSTRACT FROM AUTHOR]

Objective: There are currently 2 representative diagnostic criteria for essential thrombocythemia (ET), the 2014 British Committee for Standards in Hematology Guidelines (BCSH) criteria and the 2016 World Health Organization (WHO) criteria. We compare and discuss the advantages and disadvantages of the 2 criteria. Method: We applied the 2 criteria to 403 patients with thrombocytosis and suspected myeloproliferative neoplasms (MPN) and compared patient populations. Results: The BCSH criteria diagnosed ET in 279 patients (BCSH-ET) whereas the WHO criteria diagnosed ET in 203 patients (WHO-ET). There were 83 patients diagnosable only by the BCSH criteria (BCSH-only-ET), of which under the WHO classification, 69 patients fell under the category of MPN, unclassifiable (MPN-u), 12 patients were PMF, prefibrotic/early stage (pre-PMF), and 2 patients were polycythemia vera. Patient characteristics such as age, hemoglobin, hematocrit, platelet counts, lactate dehydrogenase levels, JAK2V617F allele burdens, prevalence of myelofibrosis and splenomegaly, and frequencies of thrombotic events and treatment did not differ between WHO-ET and BCSH-only-ET, but BCSH-only-ET patients showed higher WBC counts and higher JAK2V617F mutation frequencies. Conclusion: The BCSH criteria diagnosed ET in a broader range of patients encompassing a significant number of patients who would otherwise be diagnosed as pre-PMF or MPN-u. [ABSTRACT FROM AUTHOR]