Cardiac Safe Transplants for Systemic Sclerosis
Cardiac Safe Transplants for Systemic Sclerosis
This study is designed to treat systemic sclerosis (scleroderma) patients with an autologous
 stem cell transplant using a regimen of immune suppressant drugs and chemotherapy that is
 less toxic to your heart.
The autologous hematopoietic stem cell transplant used in this research study is an
 investigational procedure that uses cyclophosphamide and fludarabine (chemotherapy), rabbit
 anti-thymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be
 causing your disease), and rituximab (a biologic drug that targets B cells of your immune
 system). After use of these treatments, the patient will receive their own previously
 collected blood stem cells (autologous stem cell transplant). The ability of these
 experimental treatments to stop relapses and progression (worsening) of your systemic
 sclerosis will be assessed.
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