RIC alloBMT With Post-transplant Cyclophosphamide for Refractory Systemic Sclerosis

Recipient Inclusion Criteria: All patients with moderate-to-severe SSc will be considered for this trial, including women and minorities. SSc is too rare a disease in children for it to be feasible to include them. Patients must meet the following criteria to be eligible for participation in this clinical trial: 1. 2013 ACR/EULAR Criteria for Systemic Sclerosis 2. Active diffuse cutaneous disease with an mRSS ≥ 20 - including increasing skin score, new body areas involved, increased thickening in previously affected body areas, severe pruritus, tendon friction rubs OR concern for active interstitial lung disease (ILD) with FVC\<70% of predicted, new fibrosis/GGO on HRCT, and/or falling FVC \>10% of predicted 3. Lack of response to first line therapy including mycophenolate mofetil at maximum tolerated dose (up to 1.5 grams BID) after 10 weeks and/or equivalent degree of immunosuppression/immunomodulatory therapy with MTX, CYC, IVIG, or rituximab. Lack of response can include physician judgement based on review of records and patient report. 4. Age \>18 years and ≤ 65 years 5. Patients should be eligible for transplantation according to the BMT Policy Manual. 6. Female patients (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months post-transplant. Effective birth control is defined as the following: * Abstinence * Consistently use birth control pills or patch * Use injectable birth control (for example, Depo-Provera or Norplant) * Have tubal sterilization * Have placement of an IUD 7. Use of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam every time you have vaginal sex. Male patients (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant. Effective birth control methods include: * Abstinence * Vasectomy or female partner who had a tubal ligation * Use of condoms with contraceptive foam 8. Adequate organ function\* defined as: 1. Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 45%. without evidence of pulmonary arterial hypertension (defined as resting pulmonary arterial systolic pressure (PASP) \> 40 mmHg or mean pulmonary arterial pressure (mPAP) \> 25 mmHg). 2. Hepatic: Total bilirubin \< 3.0 x the upper limit of normal (ULN) (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.0 x ULN. 3. Renal: estimated creatinine clearance ≥ 40 mL/minute (using the Cockcroft-Gault formula and actual body weight). Cockcroft-Gault formula, based on ideal body weight (IBW): Creatinine clearance (CrCl) = (140 - age) x IBW (kg) x 0.85 for females/polymerase chain reaction (PCr) x 72 d. Pulmonary: DLCO (corrected/adjusted for hemoglobin) \> 40% and forced expiratory volume (FEV1) \> 50% predicted (without administration of bronchodilator) and FVC \> 50% predicted. * Patients not meeting eligibility for adequate organ function may still be eligible for the study if deemed reasonably safe and clinically appropriate by the investigator following consultation with the appropriate specialist (e.g., cardiology, nephrology, or pulmonology). 9. Karnofsky performance score\>70% 10. Patients with a history of hepatitis B virus (HBV) infection must be on suppressive therapy, if indicated, with undetectable HBV viral load within 6 months. 11. Patients with a history of hepatitis C virus (HCV) infection must have received prior treatment or must be receiving treatment currently with undetectable HCV viral load within 6 months. Donor inclusion criteria: 1. HLA-matched or -haploidentical, parent, child, sibling, or half-sibling of the recipient 2. Eligible as per donor selection in FDA 21 Code of Federal Regulations (CFR) Part 1271 3. Meets all requirements for bone marrow donor selection criteria as described in the standard Johns Hopkins BMT Policies and Procedures.Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need as determined by the principal investigators. Medically healthy with no clinically significant findings in the physical examination, medical history, vital signs which, in the judgment of the investigator, would inappropriately jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; 4. No history of any clinically significant immunosuppressive or autoimmune disease including hematologic malignancy or history of solid organ or allogeneic bone marrow transplantation; 5. Ability to understand and provide informed consent for all study procedures including bone marrow harvest. Recipient Exclusion Criteria: 1. Pregnant, breast feeding, or considering becoming pregnant during the course of the study; 2. Requiring IV antimicrobial treatment or hospitalization within 7 days prior to study enrollment for known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds); 3. History of human immunodeficiency virus (HIV) infection; 4. Active or unresolved gastric antral vascular ectasia (GAVE) syndrome; 5. Active or unresolved scleroderma renal crisis; 6. Clinically significant pulmonary hypertension, interstitial lung disease, or other cardiopulmonary disease with inadequate organ function as defined above\*\*; 7. Any illness or condition which, in the judgment of the investigator, would inappropriately jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; 8. Known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; 9. Prisoners or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness; 10. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; 11. History of significant allergic reactions, hypersensitivity, or intolerance attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study. * Patients not meeting eligibility for adequate organ function may still be eligible for the study if deemed reasonably safe and clinically appropriate by the investigator following consultation with the appropriate specialist (e.g., cardiology, nephrology, or pulmonology).