To learn if giving ruxolitinib and busulfan before a stem cell transplant can help to reduce spleen size and help the transplant to succeed.

Primary Objective

1) Compare the proportion of patients alive, disease free, engrafted, and without poor graft function at 100 days post-transplant with the historical rate of 45%.

Secondary Objectives:

1. Overall survival
2. Progression-free survival
3. Graft vs host disease relapse free survival
4. Relapse rate
5. Non-relapse Mortality
6. Time to Neutrophil and platelet engraftment
7. Time to red cell transfusion independence
8. Graft failure
9. Acute and chronic GVHD
10. Grade 3 -5 Toxicity
11. Incidence of poor graft function5
12. Need for growth factors (myeloid or thrombopoietic) at 100 days
13. Spleen response around day -7, -1, 30, and 100 days
14. Need for transfusions at 100 days
15. Time to discontinuation of immunosuppressives

Exploratory Objectives:

1. Immune reconstitution
2. Cytokine profile

Inclusion Criteria:

1. Participants 18 years to less than or equal to 75 years.

2. Able to provide written consent.

3. Primary or secondary Myelofibrosis (may have received Jak inhibitors including ruxolitinib)

4. Enlarged spleen by palpation or imaging. For the purpose of this study, splenomegaly is defined as any clinically palpable spleen or spleen larger than 12 cms on imaging.

5. Has a fully matched (8/8:HLA A, B, C, DRB1) related or matched unrelated donor.

6. Adequate renal function, including:

   a. Serum creatinine </= 1.5 mg/dL or estimated Glomerular Filtration Rate (eGFR using the CKI-EPI equation) >/= 40 ml/min/1.73 m2.

7. Adequate liver function, including:

   1. ALT/AST \