Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis

Eligibility 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 (or legally authorized representative). 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 willing to continue until 9-12 months post-transplant as tolerated
• * 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
• * 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