Allogeneic Hematopoietic Cell Transplantation for Severe Systemic Sclerosis

Inclusion Criteria: * Patients eligible for the study must have a human leukocyte antigen (HLA)-identical sibling or HLA-matched unrelated bone marrow donor available and willing to donate. * Patients with severe SSc as defined by the American College of Rheumatology and at high-risk for a fatal outcome based on the following prognostic factors in groups 1-5: * Group 1: Patients must have 1) both a and b below; and 2) at least one of c, d or e: * a. diffuse cutaneous scleroderma with skin score of greater than or equal to 16 (modified Rodnan scale \[mRSS\]). * b. duration of systemic sclerosis less than or equal to 7 years from the onset of first non-Raynaud's symptom. * c. presence of interstitial lung disease (either forced vital capacity \[FVC\] or corrected diffusing capacity of the lung for carbon monoxide \[DLCOcorr\] less than 70 % of predicted) and evidence of alveolitis (abnormal bronchoalveolar lavage (BAL) or high resolution chest computed tomography \[CT\] scan) after treatment with intravenous cyclophosphamide greater than or equal 2 grams given over at least a 3 month period; for patients not able to adequately complete pulmonary function tests (PFT), there must be evidence of progressive disease on chest CT. * d. left heart failure with left ventricular ejection fraction (LVEF) \< 50% (that has responded to treatment targeted to scleroderma); 2nd or 3rd atrioventricular (AV) block with other evidence of cardiomyopathy related to SSc; myocardial disease not secondary to SSc must be excluded by a cardiologist. * e. history of SSc-related renal disease that is not active at the time of screening; history of scleroderma hypertensive renal crisis is included in this criterion. * Group 2: Progressive pulmonary disease as defined by a decrease in the FVC or DLCOcorr by 15 percent or greater compared to a prior FVC or DLCOcorr in the previous twelve month period; in addition, patients may have either less skin involvement than group 1 (mRSS less than 16) and the FVC or DLCOcorr is less than 70% or both FVC and DLCOcorr greater than or equal to 70% if they have diffuse cutaneous disease (mRSS greater than 16) at screening for the study; patients must also have evidence of alveolitis as defined by abnormal chest CT or BAL; for patients not able to adequately complete PFT, there must be evidence of progressive disease on chest CT. * Group 3: Have progressive active SSc after prior autologous transplant based on the presence of progressive pulmonary disease; this will be defined by a decrease in the FVC or DLCO adjusted since prior autologous transplant of 15 percent or greater of the pre-transplant percent predicted value, in addition to evidence of alveolitis as defined by chest CT changes or BAL. If patients had prior autologous HCT on the "Scleroderma: Cyclophosphamide Or Transplantation" (SCOT) clinical trial, they must have failed based on the defined study endpoints and be approved by the protocol principal investigator (PI). * Group 4: Patients who meet group 1 inclusion criteria but may have FVC or DLCO-adjusted less than 70% plus have had an adverse event on cyclophosphamide preventing its further use (specifically hemorrhagic cystitis, leukopenia with white blood cell \[WBC\]\< 2000 or absolute neutrophil count \[ANC\] \< 1000 or platelet count \< 100,000). * Group 5: Diffuse scleroderma with disease duration less than or equal to 2 years since development of first sign of skin thickening plus modified Rodnan skin score greater than or equal to 25 plus erythrocyte sedimentation rate (ESR) \> 25 mm/1st hour and/or hemoglobin (Hb) \< 11 g/dL, not explained by causes other than active scleroderma. * Unless patients have a DLCO-adjusted less than 45%, patients in all groups must have failed either oral or intravenous cyclophosphamide regimen defined as: IV cyclophosphamide administration for at least \> 3 months between first and last cyclophosphamide dose at a total cumulative IV dose of at least 2 grams, oral cyclophosphamide administration for \> 4 months regardless of dose, or combination of oral and IV cyclophosphamide for at least \> 6 months independent of dose. * DONOR: HLA genotypically identical sibling or unrelated donor; unrelated donors are required to be matched by standard molecular methods at the intermediate resolution level at HLA-A, B, C and DRB1 and the allele level at DQB1. * DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines * DONOR: Bone marrow is the preferred cell source Exclusion Criteria: * Fertile men or women unwilling to use contraceptive techniques during and for 12 months following transplant * Evidence of ongoing active infection * Pregnancy * Patients with a creatinine clearance \< 60 ml/min/1.73 m\^2 body surface area * Uncontrolled clinically significant arrhythmias * Clinical evidence of significant congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class III or IV) * LVEF \< 45% by echocardiogram * Severe pulmonary dysfunction with a hemoglobin corrected DLCO \< 30% or FVC \< 40% of predicted or O2 saturation \< 92% at rest without supplemental oxygen * Significant uncontrolled pulmonary hypertension defined as: Pulmonary artery peak systolic pressure \> 55 mmHg by echocardiogram, or pulmonary artery peak systolic pressure 45-55 mmHg by echocardiogram and mean pulmonary artery pressure by right heart catheterization exceeding 25 mmHg at rest (or 30 mmHg with exercise); or NYHA/World Health Organization (WHO), Class III or IV * Active hepatitis or liver biopsy evidence of cirrhosis or periportal fibrosis; liver function tests: total bilirubin \> 2 x the upper limit of normal and/or serum glutamic pyruvate transaminase (SGPT) and SGPT \> 4 x the upper limit of normal * Patients with poorly controlled hypertension * Patients whose life expectancy is severely limited by illness other than autoimmune disease * Patients with poorly controlled bleeding from gastric antral vascular ectasia (GAVE) or other gastrointestinal (GI) sites * Untreated psychiatric illness, drug/alcohol abuse * Inability to give voluntary informed consent or guardian's informed consent * Demonstrated lack of compliance with prior medical care * Malignancy within the 2 years prior to treatment, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ; treatment must have been completed (with the exception of hormonal therapy for breast cancer) with cure/remission status verified for at least 2 years at time of treatment * Human immunodeficiency virus (HIV) seropositivity * DONOR: Identical twin * DONOR: Current pregnancy * DONOR: HIV seropositivity * DONOR: Deemed medically unable to undergo bone marrow harvesting * DONOR: Current serious systemic illness including uncontrolled infections * DONOR: Failure to meet institutional criteria for donation as described in the Standard Practice Guidelines