Cardiac Safe Transplants for Systemic Sclerosis

Inclusion Criteria: 1. Age 18 - 65 years old at the time of pre-transplant evaluation 2. An established diagnosis of systemic sclerosis 3. Diffuse cutaneous systemic sclerosis with involvement proximal to the elbow or knee and a modified Rodnan Skin Score of ≥ 14 (see Appendix A) AND Any one of the following: 1. DLCO \< 80% of predicted or decrease in lung function (DLCO, DLCO/VA or FVC) of 10% or more over 12 months. 2. Pulmonary fibrosis or alveolitis on CT scan or chest x-ray (ground glass appearance of alveolitis). 3. Abnormal EKG (non-specific ST-T wave abnormalities, low QRS voltage, or ventricular hypertrophy), or pericardial effusion or pericardial enhancement without constriction on MRI 4. Gastrointestinal tract involvement confirmed on radiological study. Radiologic findings of scleroderma are small bowel radiographs showing thickened folds with dilated loops, segmentation, and flocculation +/- diverticula, or pseudodiverticula. A hide-bound appearance may be present (e.g. dilated and crowded circular folds). GI involvement may also be confirmed by D-xylose malabsorption, patulous esophagus on high-resolution computed tomography (HRCT), or esophageal manometry. OR Limited cutaneous systemic sclerosis (SSc) (modified Rodnan Skin Score \<14) with lung involvement defined as active alveolitis on bronchoalveolar lavage (BAL), ground-glass opacity on CT scan, a DLCO \< 80% predicted, or decrease in lung function (DLCO/VA, DLCO, FVC) of 10% or more in last 12 months. Other Inclusion Criteria for "CAST" Conditioning Regimen (presence of any of the following): 1. Septal flattening or D-sign on MRI (without deep breathing) 2. PASP \>40 mm Hg or \>45 mm Hg with fluid challenge\* 3. mPAP \>25 mm Hg or \>30 mm Hg with fluid challenge\* 4. Non-ischemia diffuse ventricular hypokinesis or non-ischemia wall hypokinesis * Fluid challenge is 1000 ml normal saline over 10 minutes. Fluid challenge will not be done if right atrial pressure is \>13 mm Hg at rest or pulmonary capillary wedge pressure is \>20 mm Hg at rest. Exclusion Criteria: 1. Active ischemic heart disease or untreated coronary artery disease 2. Untreated life-threatening cardiac arrhythmia on EKG or 24-hour holter 3. Pericardial effusion \> 1 cm on cardiac MRI unless successful pericardiocentesis has been performed 4. LVEF \<35% 5. End-stage lung disease characterized by TLC\<45% of predicted value, or DLCO hemoglobin corrected \< 30 % predicted. 6. Creatinine clearance \<40 by 24-hour urine 7. History of breast implants that have not been removed (unless they cannot be surgically removed due to risks of surgery) 8. Liver cirrhosis, transaminases \>2x of normal limits, or bilirubin \> 2.0 unless due to Gilbert's disease 9. Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment 10. Prior history of malignancy 11. Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy 12. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible 13. Major hematological abnormalities such as platelet count \< 100,000/ul or absolute neutrophil count (ANC) \< 1000/ul 14. HIV positive 15. Hepatitis B or C positive 16. PASP \>50 mmHg without fluid challenge 17. mPAP \>34 mmHg without fluid challenge 18. Coronary artery disease not reversed by cardiology and interventional radiology