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The goals of treatment for patients with myelofibrosis should be to improve length and quality of life. Clinical trials must be designed with these goals in mind, with endpoints focused on overall survival and symptom reduction, as opposed to surrogate endpoints such as spleen volume reduction. The treatment landscape for MF is evolving rapidly. The most effective therapies or combinations of therapies will likely simultaneously impact both the malignant hematopoietic stem cell and mechanisms of aberrant fibrogenesis that drive this dise