Selinexor Monotherapy for Cytoreduction in BCR::ABL1-Negative Myeloproliferative Neoplasms

Inclusion Criteria:

* Aged 18 to 80 years at the time of informed consent.
* Diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasm, including polycythemia vera, essential thrombocythemia, or primary myelofibrosis, according to World Health Organization criteria.
* Presence of an indication for cytoreductive therapy, including at least one of the following:
* Extreme thrombocytosis, defined as platelet count \>1500 x 10\^9/L.
* Progressive leukocytosis, defined as white blood cell count \>25 x 10\^9/L.
* Symptomatic splenomegaly documented by imaging.
* Severe disease-related symptoms, such as significant weight loss within the past 6 months.
* Unwillingness or inability to tolerate standard cytoreductive therapies, such as hydroxyurea or interferon.
* Eastern Cooperative Oncology Group performance status of 0 to 2.
* Adequate organ function, including renal, hepatic, cardiac, and coagulation function, as determined by laboratory tests and clinical evaluation in the opinion of the investigator.
* Adequate baseline hematologic function without recent transfusion or growth factor support.
* Ability to comply with study procedures, visits, and assessments.
* Ability to understand and willingness to sign a written informed consent form.
* For women of childbearing potential, a negative pregnancy test before study entry.
* For participants of reproductive potential, agreement to use effective contraception during the study and for at least 120 days after the last dose of study drug.

Exclusion Criteria:

* Diagnosis of Philadelphia chromosome-positive myeloproliferative neoplasm or chronic myeloid leukemia.
* Concurrent acute leukemia or other active hematologic malignancy.
* Severe or uncontrolled comorbid condition, including but not limited to significant cardiac or pulmonary disease, decompensated liver disease, or end-stage renal disease.
* Active uncontrolled bacterial, viral, or fungal infection.
* Active gastrointestinal disorder associated with significant bleeding or impaired drug absorption.
* Significant neurologic or psychiatric disorder that may interfere with study participation or compliance.
* Known hypersensitivity to selinexor or any of its components.
* Receipt of another investigational agent or participation in another interventional clinical trial within 4 weeks before enrollment.
* Recent receipt of cytotoxic chemotherapy, radiotherapy, immunotherapy, or other cytoreductive treatment before study entry.
* History of substance abuse, alcohol dependence, or illicit drug use that may interfere with adherence to study requirements.
* Another active malignancy requiring systemic treatment.
* Clinically significant bleeding disorder, severe coagulopathy, or requirement for long-term therapeutic anticoagulation.
* Receipt of a live vaccine within 30 days before the first dose of study drug, or planned receipt of a live vaccine during the study.
* Known active infection with human immunodeficiency virus or active viral hepatitis.
* Estimated life expectancy of less than 12 weeks.
* Inability to provide informed consent due to cognitive impairment or severe psychiatric illness.
* Any condition that, in the investigator's judgment, would make the participant unsuitable for participation in this study.