Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis

You may be eligible if

• Diagnosis of primary or secondary Myelofibrosis with transplant indication by DIPSS-plus (\> intermediate -1);
• Age 18-70; patients \>/= age 50 must have an comorbidity score (HCT-CI) \</= 4 (Sorror). The Principal Investigator is the final arbiter for comorbidity;
• Patients can be in chronic phase (CP) with BM blast count \</= 10% or after progression to AML and achieved \</= 5% BM blasts (morphologic CR prior to transplant);
• Lack of an HLA matched donor or need to proceed fast to transplantation when a patient does not have an immediately available matched unrelated donor (typed by high-resolution in the registry);
• Performance status \>/=70% (Karnofsky); patients \> 50 years should have adequate cognitive function; any concerns regarding cognitive function should be addressed by a Geriatrician/Neurologist;
• Adequate organ function: ALT/AST/billirubin \</= 5X UNL, creatinine clearance \> 50mls/min (calculated with Cockroft-Gault formula); LVEF \>/= 50%, DLCOc \>/= 50%;
• Prior treatment with JAK2 inhibitor therapy is not excluded. Patients on a JAK2 inhibitor may continue through conditioning until Day -3 then tapered at the discretion of the investigator.
• Exclusion:
• Evidence of portal hypertension with varices, ascites, or hepatic encephalopathy;
• -\>10% bone marrow blasts at transplant if no history of AML and \>5% if had previous progression to AML;
• HIV positive; active hepatitis B or C;
• Patients with active infections. The PI is the final arbiter of the eligibility;
• Liver cirrhosis;
• Prior CNS involvement by tumor cells;
• Severe pulmonary hypertension (PHT) (On echo or right side cardiac catheterization);
• History of another primary malignancy that has not been in remission for at least 3 years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully excised melanoma in situ \[Stage 0\], curatively treated localized prostate cancer, and cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear);
• Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization;
• Noncompliance - Inability or unwillingness to comply with medical recommendations regarding therapy or follow-up, including smoking tobacco. Smoking cessation is a standard teaching practice prior to admission for all patients undergoing stem cell transplant. Any patient who refuses to stop smoking prior to transplant will not be eligible for this study.