Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis

Inclusion Criteria: Recruitment Part: * Documented diagnosis of pre-fibrotic primary myelofibrosis (pre-fibrotic PMF), overt PMF, post-polycythemia MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF) confirmed by bone marrow biopsy * Have been tested or have results available for phenotypic driver mutations (JAK2/CALR/MPL) and high molecular risk (HMR) mutations using a broad myeloid malignancies targeted gene panel. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Able to provide informed consent * Adequate organ function * Donor search initiated or patient is agreeable to donor search * Meet the definition/criteria for high-risk myelofibrosis Study Arm Allocation: * Grade of fibrosis on bone marrow biopsy available according to World Health Organization (WHO) criteria * Results available for phenotypic driver mutations (JAK2/CALR/MPL) and targeted sequencing results using a broad myeloid malignancy panel with a minimal requirement to include results on High molecular risk (HMR) mutations such as ASXL1/EZH2/IDH1/IDH2/SRSF2/U2AF1/TP53 * ECOG performance status 0-2 * Adequate organ function * Information on donor search and donor type available Exclusion Criteria: Recruitment Part: * Blasts in peripheral blood or bone marrow ≥10% * For patients already on ruxolitinib at study entry, and meet the criteria of ruxolitinib failure * Previous history of transformation to blast phase or acute myeloid leukemia * Received allogeneic stem cell transplant for myeloproliferative neoplasm * Presence of an active uncontrolled infection * Myocardial infarction in the preceding 3 months * Active hepatitis A, B or C * Known human immunodeficiency virus (HIV) positive * History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer * Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation. * Pregnant or breastfeeding women Study Arm Allocation: * Blasts in peripheral blood or bone marrow ≥10% * Meet the criteria of ruxolitinib failure * Presence of an active uncontrolled infection * Myocardial infarction in the preceding 3 months * Active hepatitis A, B or C * Known HIV positive * History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer * Pregnant or breastfeeding women * Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation. * Time between registration and allocation of study arm \>24 weeks