JAK Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis

Inclusion Criteria

PART 1:

• PART 1: Disease criteria
• Diagnosis of primary MF (PMF) as defined by the 2008 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) or DIPSS-plus scoring system
• PART 1: Ability to understand and the willingness to sign a written informed consent document
• PART 1: Patient must be a potential hematopoietic stem cell transplant candidate

PART 2:

• PART 2: 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
• PART 2: Received ruxolitinib for at least 8 weeks immediately prior to conditioning and be able to continue until Day -4 pre-transplant
• PART 2: Performance status score
• Karnofsky >= 70
• PART 2: Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hr urine creatinine clearance must be > 60 ml/min
• PART 2: Total serum bilirubin must be 3 mg/dL, and symptomatic biliary disease will be excluded
• PART 2: Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal
• May not be on supplemental oxygen
• PART 2: Left ventricular ejection fraction > 40% OR
• PART 2: Shortening fraction > 26%
• PART 2: Comorbidity Index 5/6 match > 4/6 match); additional CB units then may be selected to achieve the required cell dose, as outlined below; if a second unit is required, this unit will be the unit that most closely HLA matches the patient and meets minimum size criteria outlined below of at least 1.5 x 10^7 total nucleated cells (TNC)/kg (i.e. a smaller, more closely matched unit will be selected over a larger, less well matched unit as long as minimum criteria are met)
• If two CB units are used:
• The total cell dose of the combined units must be at least 3.0 x 10^7 TNC per kilogram recipient weight
• Each CB unit MUST contain at least 1.5 x 10^7 TNC per kilogram recipient weight
• Algorithm for determining single versus double unit cord blood transplant:
• Match grade 6/6: TNC dose >= 2.5 x 10^7/kg
• Match grade 5/6, 4/6: TNC dose >= 4.0 (+/- 0.5) x 10^7/kg
• DONOR: General comments:
• Units will be selected first based on the TNC dose and HLA matching
• Cluster of differentiation (CD)34+ cell dose will not be used for unit selection unless 2 units of equal HLA-match grade are available; in this case, the unit with the larger CD34+ cell dose (if data available) should be selected
• A CB unit that is 5/6 mismatched but homozygous at the locus of mismatch should be chosen over a 5/6 unit with bidirectional mismatch even if the latter unit is larger (has more cells); this also applies to 4/6 units; this is only applicable to choosing units within a given match grade
• Other factors to be considered:
• Within the same HLA match grade, matching at DR takes preference
• Cord blood banks located in the United States are preferred
• Up to 5% of the cord blood product(s), when ready for infusion, may be withheld for research purposes as long as thresholds for infused TNC dose are met; these products will be used to conduct studies involving the kinetics of engraftment and immunobiology of double cord transplantation

Exclusion Criteria

PART 1:

• PART 1: Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
• PART 1: Uncontrolled viral, bacterial, or fungal infections at the time of study enrollment
• PART 1: History of prior allogeneic transplant
• PART 1: Pregnant or breastfeeding (only if patients have not been star