Inclusion Criteria:

• - PART 1: JAK INHIBITOR ADMINISTRATION INCLUSION CRITERIA.

• - Age > 18 years.

• - Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary MF as defined by the International Working Group (IWG) for Myeloproliferative Neoplasms Research and Treatment criteria.

• - Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System (DIPSS)-plus scoring system (DIPSS may be used if all data from DIPSS are not available) - Ability to understand and the willingness to sign a written informed consent document (or legally authorized representative) - Patient must be a potential hematopoietic stem cell transplant candidate.

• - PART 2: ALLOGENEIC STEM CELL TRANSPLANT INCLUSION CRITERIA.

• - Meeting criteria for 1st phase as above, at time of initiation of JAK inhibitor, including ability to understand and willingness to sign a written informed consent.

Patients arriving to our institution for transplant and not enrolled in Part 1 may still be enrolled in Part 2 if Part 1 criteria met. These patients will have Part 1 endpoints transcribed from medical records.

• - Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be able to continue until day -4 pre-transplant.

• - Karnofsky performance status score >= 70.

• - Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hour (hr) urine creatinine clearance must be > 60 ml/min.

• - Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis.

• - Transaminases must be < 3 x the upper limit of normal.

• - Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension.

Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded.

• - Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal; may not be on supplemental oxygen.

• - Left ventricular ejection fraction > 40% OR shortening fraction > 26% - Comorbidity Index < 5 at the time of pre-transplant evaluation.

• - DONOR: Patients must be screened prior to transplant for donor-specific anti-HLA antibodies (DSA).

Patients with DSA will be reviewed by the principal investigator and considered for desensitization treatment.

• - DONOR: Children are preferred over siblings and parents.

• - DONOR: Younger donors are preferred over older donors.

• - DONOR: ABO matched donors are preferred over minor ABO mismatched and over major ABO mismatch donors.

Exclusion Criteria:

• - PART 1: JAK INHIBITOR ADMINISTRATION EXCLUSION CRITERIA.

• - Contraindication to receiving a JAK inhibitor including: - Patients who have known hypersensitivity to JAK inhibitors.

• - Clinical or laboratory evidence of significant renal or hepatic impairment including cirrhosis.

• - Active uncontrolled infection.

• - Known human immunodeficiency virus (HIV) positivity.

• - Women who are pregnant or trying to conceive.

• - Caution should be used in patients with platelets < 100 though adjustments in dose can be made to accommodate anyone with platelets > 50.

• - History of prior allogeneic transplant.

• - Leukemic transformation (> 20% blasts) - PART 2: ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION CRITERIA.

• - Uncontrolled viral or bacterial infection at the time of study enrollment.

• - Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval.

• - Known HIV positivity.

• - Pregnant or breastfeeding.

- Availability of an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related donor or an HLA 10 of 10 matched unrelated donor

OUTLINE: JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of hematopoietic cell transplantation (HCT) conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan intravenously (IV) over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo total-body irradiation (TBI) on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then orally (PO) for 6 months, mycophenolate mofetil PO twice daily (BID) or three times daily (TID) beginning day 5 for 6 weeks, and granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) beginning day 7 until neutrophil recovery is > 1,500/mm^3. All patients undergo magnetic resonance imaging (MRI), computed tomography (CT), bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) on the trial. After completion of study treatment, patients are followed up between day 80-100, at 1 year, and then up to 5 years.

Arms

Experimental: Treatment (JAK inhibitor, conditioning, GVHD prophylaxis)

JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3. All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.

Interventions

Drug: - Cyclophosphamide

Given IV

Drug: - JAK Inhibitor

Given PO

Drug: - Fludarabine

Given IV

Biological: - Recombinant Granulocyte Colony-Stimulating Factor

Given SC

Drug: - Melphalan

Given IV

Drug: - Mycophenolate Mofetil

Given PO

Procedure: - Peripheral Blood Stem Cell Transplantation

Given IV

Drug: - Tacrolimus

Given IV and PO

Radiation: - Total-Body Irradiation

Undergo TBI

Procedure: - Computed Tomography

Undergo CT

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Procedure: - Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Procedure: - Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Procedure: - Biospecimen Collection

Undergo blood sample collection

Procedure: - Echocardiography

Undergo ECHO

Procedure: - Multigated Acquisition Scan

Undergo MUGA