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

Inclusion Criteria:

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) Patients can be in chronic phase (CP) with BM blast count 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 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.