Inclusion Criteria:

• - Diagnosis of primary of secondary myelofibrosis with transplant indication by Dynamic International Prognostic Scoring System (DIPSS)-plus (> intermediate-1) - Patients >= age 50 must have a comorbidity score (hematopoietic cell transplant-comorbidity index [HCT-CI]) < 4 (Sorror) - Patients can be in chronic phase (CP) with bone marrow (BM) blast count =< 15% as long as no evidence of disease acceleration per principal investigator (PI) and treating physician's opinion or after progression to acute myeloid leukemia (AML) and achieved =< 5% BM blasts (morphologic complete remission [CR] prior to transplant) - Lack of an human leukocyte antigen (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.

• - Alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin =< 5 X upper limit of normal (ULN) - Measured creatinine clearance > 60 mls/min.

• - Left ventricular ejection fraction (LVEF) >= 50% - Corrected carbon monoxide diffusing capability (DLCOc) >= 50% - No active infections.

• - Prior treatment with JAK2 inhibitor therapy is not excluded; a JAK2 inhibitor will need to be stopped 1-2 days prior to starting conditioning regimen.

• - DONOR: Documented informed consent per local, state and federal guidelines.

• - DONOR: Genotypically haploidentical as determined by HLA typing.

• - Preferably a non-maternal HLA haploidentical relative due to data of high incidence of graft failure with use of maternal HLA haploidentical cells.

• - Eligible donors include biological parents, siblings or half-siblings, children, or cousins in rare instances.

• - DONOR: Absence of pre-existing donor-specific anti-HLA antibodies (DSA) in the recipient; Patients with pre-existing DSA could undergo desensitization per City of Hope (COH) standard operating procedures [SOP] and should have DSA < MFI of 2000 prior to conditioning at discretion of PI.

• - DONOR: Infectious disease screening performed within 30 days prior to stem cell mobilization per federal guidelines and is: - Seronegative for HIV 1+2 antibody (Ab) and/or HIV polymerase chain reaction (PCR), human T-cell leukemia virus (HTLV) I/II Ab, hepatitis B virus surface antigen (HBsAg), hepatitis B virus surface antibody (HBcAb), hepatitis C virus (HCV) Ab.

• - Negative rapid plasma reagin (RPR) for syphilis.

• - DONOR: Women of childbearing potential (WOCBP): Urine pregnancy testing performed within 7 days prior to stem cell mobilization.

• - DONOR: Is approved and completed evaluation prior to recipient initiation of the preparative regimen per institutional guidelines.

Exclusion Criteria:

• - Evidence of severe portal hypertension with evidence of decompensation either with bleeding varices, large volume ascites, or hepatic encephalopathy.

• - In a bone marrow biopsy 4 weeks prior to start of conditioning on study: - > 15% bone marrow blasts at transplant if no history of AML and per PI and treating physician's opinion of disease acceleration.

• - > 5% if had previous progression to AML.

• - Human immunodeficiency virus (HIV) positive; active hepatitis B or C.

• - Patients with active infections; the PI is the final arbiter of the eligibility.

• - Patients with evidence of severe pulmonary hypertension by echocardiogram and confirmed by a subsequent right side cardiac catheterization pre-enrollment.

• - Liver cirrhosis.

• - Prior central nervous system (CNS) involvement by tumor cells.

• - 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 papanicolaou [PAP] smear) - Positive beta human chorionic gonadotropin (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.

• - DONOR: Has undergone solid organ, stem cell, bone marrow or blood transplantation.

• - DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy.

• - DONOR: Active infection.

• - DONOR: Thrombocytopenia < 150,000 cells /mm^3 at baseline evaluation.

• - DONOR: Sero-positive for HIV-1 & 2 antibody, HTLV-I & II antibody, hepatitis B virus (HBV) and HCV.

• - DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.

• - DONOR: Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy.

- DONOR: WOCBP: Pregnant or =< 6 months breastfeeding

PRIMARY OBJECTIVE:

• I. To evaluate the safety and tolerability of reduced-intensity (fludarabine/melphalan) haploidentical hematopoietic cell transplantation (Haplo-HCT) followed by post-transplant cyclophosphamide (PTCy) in patients with advanced myelofibrosis (MF), as assessed by the evaluation of toxicities, including type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

• I. To summarize and evaluate hematologic (neutrophil and platelet) recovery.

• II. To evaluate and describe cytokine release syndrome (CRS) post haploidentical HCT in the setting of advanced myelofibrosis, as assessed by grade, frequency, severity, duration and reversibility (outcome).

• III. To estimate graft failure-free survival (GFS) at 100-days post-transplant.

• IV. To estimate overall survival (OS), progression-free survival (PFS) and cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100-days, 1-year, and 2-year post transplant.

• V. To estimate the cumulative incidence of acute graft-versus-host disease (GvHD), grade II-IV, at 100-days post-transplant (per Keystone Consensus modification of the Glucksberg criteria).

• VI. To estimate the cumulative incidence of chronic GvHD at 1-year and 2-year post transplant (per National Institutes of Health [NIH] Consensus Criteria).

• VII. To characterize the severity and extent of acute and chronic GvHD.

EXPLORATORY OBJECTIVE:

• I. To conduct correlative studies and describe inflammatory cytokine levels and GVHD biomarker levels in plasma and T cell differentiation/functions in patients enrolled onto the trial.

OUTLINE: Patients receive melphalan intravenously (IV) over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo total body irradiation (TBI) on day -1 and hematopoietic cell transplantation (HCT) on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then orally (PO) for 6 months followed by a taper, mycophenolate mofetil PO thrice daily (TID) until day 35, and glycosylated recombinant human G-CSF AVI-014 (G-CSF) IV daily until absolute neutrophil count > 1,500/mm^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed for up to 2 years.

Arms

Experimental: Treatment (combination chemotherapy, TBI, HCT)

Patients receive melphalan IV over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo TBI on day -1 and HCT on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then PO for 6 months followed by a taper, mycophenolate mofetil PO TID until day 35, and G-CSF IV daily until absolute neutrophil count > 1,500/mm^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.

Interventions

Procedure: - Allogeneic Hematopoietic Stem Cell Transplantation

Undergo HCT

Drug: - Cyclophosphamide

Given IV

Drug: - Fludarabine

Given IV

Biological: - Glycosylated Recombinant Human G-CSF AVI-014

Given IV

Other: - Laboratory Biomarker Analysis

Correlative studies

Drug: - Melphalan

Given IV

Drug: - Mycophenolate Mofetil

Given PO

Drug: - Tacrolimus

Given IV or PO

Radiation: - Total-Body Irradiation

Undergo TBI