Inclusion Criteria:

- GROUP 1:

- Patients must have 1) both a and b below; and 2) at least one of c, or d

- a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to
the elbows and knees and/or involving the torso in addition to distal
extremity involvement; a skin score will be obtained but not used to
determine eligibility

- b) Duration of systemic sclerosis =< 7 years from the onset of first
non-Raynaud's symptom; for those patients with disease activity between 5-7
years from the onset of first non-Raynaud's symptom, recent progression or
activity of disease must be documented

- c) Presence of SSc-related pulmonary disease with forced vital capacity
(FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide
(DLCO) < 70% of predicted AND evidence of alveolitis by high-resolution
chest computed tomography (CT) scan and/or by bronchoalveolar lavage (BAL)
(if high resolution computed tomography [HRCT] fails to show ground glass,
then BAL for diagnosis of alveolitis must be confirmed); alveolitis by BAL
cell count will be defined based on a BAL cell differential count (> 3%
neutrophils and/or > 2% eosinophils) from any lavaged lobe

- d) History of SSc-related renal disease that may not be active at the time
of screening; stable serum creatinine must be documented for a minimum of 3
months post-renal crisis at the time of the baseline visit; history of
scleroderma hypertensive renal crisis is included in this criterion and is
defined as follows:

- History of new-onset hypertension based on any of the following (measurements
must be repeated and confirmed at least 2 hours apart within 3 days of first
event-associated observation, with a change from baseline):

- Systolic blood pressure (SBP) >= 140 mmHg

- Diastolic blood pressure (DBP) >= 90 mmHg

- Rise in SBP >= 30 mmHg compared to baseline

- Rise in DBP >= 20 mmHg compared to baseline

- AND one of the following 5 laboratory criteria:

- Increase of >= 50 % above baseline in serum creatinine

- Proteinuria: >= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5

- Hematuria: >= 2+ by dipstick or > 10 red blood cell
(RBC)s/hematopoietic-promoting factor (HPF) (without menstruation)

- Thrombocytopenia: < 100,000 platelets/mm^3

- Hemolysis: by blood smear or increased reticulocyte count

- The above definition of SSc hypertensive renal crisis is independent of whether
concomitant anti-hypertensive medications are used

- Subjects who present with solely skin and renal disease in the absence of other
organ involvement, except classic SSc renal crisis as described above and
including non-hypertensive renal crisis, must see a nephrologist to confirm that
their renal disease is secondary to only SSc

- Note: Subjects may be re-screened if they fail to meet inclusion criteria on
initial evaluation

- GROUP 2:

- Progressive pulmonary disease as defined by a decrease in the FVC or
DLCO-adjusted by 10 or 15 percent or greater, respectively, from a prior FVC or
DLCO-adjusted in the previous 18-month period

- Patients will have diffuse cutaneous disease and may have both FVC and DLCOcorr
>= 70% at screening for the study

- Patients must also have evidence of alveolitis as defined by abnormal chest
computed tomography (CT) or bronchoalveolar lavage (BAL)

- GROUP 3: Diffuse scleroderma with disease duration =< 2 years since development of
first sign of skin thickening plus modified Rodnan skin score >= 25 plus either

- Erythrocyte sedimentation rate (ESR) > 25 mm/1st hour and/or hemoglobin (Hb) <
11 g/dL, not explained by causes other than active scleroderma

- Lung involvement (either FVC or DLCO < 80% and evidence of interstitial lung
disease by CT scan or alveolitis by BAL)

- GROUP 4: Diffuse scleroderma with disease duration =< 2 years and skin score >= 30

- GROUP 5:

- Limited cutaneous scleroderma and SSc-related pulmonary disease with FVC < 80%
or hemoglobin-adjusted DLCO < 70% of predicted

- AND evidence of alveolitis by high-resolution chest CT scan and/or by BAL (if
HRCT fails to show ground glass, then BAL for diagnosis of alveolitis must be
confirmed)

- Alveolitis by BAL cell count will be defined based on a BAL cell differential
count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe

- GROUP 6: Progressive gastrointestinal disease as defined by all of the following
items:

- Disease duration of scleroderma =< 2 years.

- Documented severe malabsorption syndrome requiring nutritional support; severe
malabsorption syndrome is > 10% weight loss and on total parenteral nutrition
(TPN) or enteral feedings

- High score on distention/ bloating scale (>= 1.60 out of 3.00) on
gastrointestinal (GI) questionnaire

Exclusion Criteria:

- Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their
ability to receive cytoreductive therapy and compromise their survival; this
includes, but is not restricted to, subjects with any of the following:

- Pulmonary dysfunction defined as:

- Severe pulmonary dysfunction with (1) a hemoglobin corrected DLCO < 45% of
predicted at the Clinical Review, (2) a hemoglobin-correct DLCO < 40% of
predicted at the Baseline Screening visit, or (3) FVC < 45% of predicted at the
Clinical review or Baseline Screening visit, or

- Partial pressure (pO2) < 70 mmHg or pCO2 >= 45 mmHg without supplemental oxygen,
or

- O2 saturation < 92% at rest without supplemental oxygen as measured by forehead
pulse oximeter

- Significant pulmonary artery hypertension (PAH) defined as:

- Peak systolic pulmonary artery pressure > 50 mmHg by resting echocardiogram will
require right heart catheterization; if pulmonary artery pressure (PAP) is not
evaluable on echocardiogram due to lack of a Tricuspid regurgitant jet, then
normal anatomy and function as evidenced by normal right atrium and ventricle
size, shape and wall thickness and septum shape must be documented to rule-out
PAH; otherwise, right heart catheterization is indicated; prior history of PAH
but controlled with medications will not exclude patients from the protocol; PAH
is considered controlled with medications if peak systolic pulmonary artery
pressure is < 45 mmHg or mean pulmonary artery pressure by right heart
catheterization is < 30 mmHg at rest

- Mean pulmonary artery pressure by right heart catheterization exceeding 30 mmHg
at rest; if mean PAP is elevated and pulmonary vascular resistance and
transpulmonary gradient are normal then the patient is eligible for the protocol

- New York Heart Association (NYHA)/World Health Organization Class III or IV

- Cardiac: Uncontrolled clinically significant arrhythmias; clinical evidence of
significant congestive heart failure (CHF) (NYHA Class III or IV); left ventricular
ejection fraction (LVEF) < 50% by echocardiogram or prior insertion of a pacemaker or
cardioverter-defibrillator

- History/presence of arrhythmia (even controlled) on chemical anti-arrhythmic(s) must
have cardiac consult prior to randomization to ensure the subject could safely
proceed with protocol requirements

- Significant renal pathology defined as:

- Estimated creatinine clearance (CrCl) < 40 mL/min (using Cockcroft-Gault formula
based on actual body weight) and serum creatinine > 2.0 mg/dL; OR

- Active, untreated SSc renal crisis at the time of enrollment; presence of
nephrotic range proteinuria (defined as >= 3.5 gms/24 hours, or
protein:creatinine ratio >= 3.5), active urinary sediment, urinary RBCs > 25 per
HPF, or red cell casts require further investigation by a nephrologist to rule
out glomerulonephritis, overlap syndromes, or other causes of renal disease in
all subjects; subjects with glomerulonephritis or overlap syndromes will be
excluded

- Hepatic: Active hepatitis (alanine aminotransferase [ALT], aspartate aminotransferase
[AST], or bilirubin > 2 times the upper limit of normal [ULN]) or evidence of
moderate to severe periportal fibrosis by liver biopsy

- Active or clinically significant Gastric Antral Vascular Ectasia (GAVE, "watermelon
stomach")

- Unwilling or unable to discontinue disallowed disease-modifying antirheumatic drugs
(DMARDs) for treatment of SSc at time of randomization

- History or presence of a 2nd autoimmune disease requiring immunosuppressive therapy
that has substantial risk of immunosuppressive treatment beyond transplant with the
following exceptions:

- History and/or presence of Sjogren's Syndrome is allowed

- Stable myositis (A history of myositis that is clinically stable as defined by
lack of progressive proximal muscle weakness and a stable or decreasing creatine
phosphokinase [CPK] < 3 x ULN) is allowed

- The presence of anti-double stranded (ds)-deoxyribonucleic acid (DNA) without
clinical systemic lupus erythematosus in a patient with a diagnosis of otherwise
"pure" SSc is allowed

- Concomitant rheumatoid arthritis without extra-articular disease characteristic
of rheumatoid arthritis is allowed

- Active uncontrolled infection that would be a contraindication to safe use of
high-dose therapy

- Positive study for Hepatitis B surface antigen or Hepatitis B or C confirmed by
polymerase chain reaction (PCR)

- Positive serology for human immunodeficiency virus (HIV)

- Absolute neutrophil count (ANC) < 1500 cells/uL

- Platelets < 100,000 cells/uL

- Hematocrit < 27%

- Hemoglobin < 9.0 g/dL

- Malignancy within the 2 years prior to randomization, 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 randomization

- Presence of other comorbid illnesses with an estimated median life expectancy < 5
years

- Evidence of myelodysplasia (MDS); subjects with history of receiving any prior
chemotherapy and/or radiotherapy for the treatment of malignant disease, history of
greater than 2 months total prior cyclophosphamide for any condition (regardless of
dose and route) and/or subjects presenting with abnormal peripheral blood counts
require unilateral bone marrow aspiration for pathology, flow cytometry,
cytogenetics, and fluorescence in situ hybridization (FISH) MDS panel (per
institutional profile) to rule out MDS

- Pregnancy

- Inability to give voluntary informed consent

- Unwilling to use contraceptive methods for at least 15 months after starting
treatment