Scleroderma: Cyclophosphamide or Transplantation

The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted ), renal failure (chronic dialysis \> 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction \<30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.

Time frame: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.

Time frame: 48 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant's hemoglobin was \<13 or \>17 gm/dL, and altitude (Calgary site only). Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>15% in DLCO % Predicted indicated disease improvement, a decrease of \>15% indicated disease worsening, and a change of \<=15% was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant's hemoglobin was \<13 or \>17 gm/dL, and altitude (Calgary site only). Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>15% in DLCO % Predicted indicated disease improvement, a decrease of \>15% indicated disease worsening, and a change of \<=15% was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>10% in FVC % Predicted indicated disease improvement, a decrease of \>10% indicated disease worsening, and a change of \<=10% was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>10% in FVC % Predicted indicated disease improvement, a decrease of \>10% indicated disease worsening, and a change of \<=10% was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome. Analysis was based on an ordinal response variable, defined as follows: a decrease of \>0.4 from baseline in the HAQ-DI score was considered disease improvement, an increase of \>0.4 was considered disease worsening, and any change less than 0.4 was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome. Analysis was based on an ordinal response variable, defined as follows: a decrease of \>0.4 from baseline in the HAQ-DI score was considered disease improvement, an increase of \>0.4 was considered disease worsening, and any change less than 0.4 was considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity. Analysis was based on an ordinal response variable, defined as follows: if the baseline mRSS was \<=20, a decrease \>=5 points from baseline indicated disease improvement and an increase \>= 5 points indicated disease worsening; if the baseline mRSS was \>20, then a decrease of \>25% indicated disease improvement and an increase of \>25% indicated disease worsening. Participants who do not meet the disease criteria outlined above were considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity. Analysis was based on an ordinal response variable, defined as follows: if the baseline mRSS was \<=20, a decrease \>=5 points from baseline indicated disease improvement and an increase \>= 5 points indicated disease worsening; if the baseline mRSS was \>20, then a decrease of \>25% indicated disease improvement and an increase of \>25% indicated disease worsening. Participants who do not meet the disease criteria outlined above were considered no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. Analysis was based on ordinal response, defined as follows for each component: a \>= 10 point increase indicated disease improvement, a \>= 10 point decrease indicated disease worsening, and a change \<10 points indicated no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. Analysis was based on ordinal response, defined as follows for each component: a \>= 10 point increase indicated disease improvement, a \>= 10 point decrease indicated disease worsening, and a change \<10 points indicated no change. Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Number of participants who experienced any event of myositis that occurred from randomization to Month 54 post-randomization. Documented myositis occurred if the participant had 1) elevated creatine phosphokinase (CPK), electromyography, and/or biopsy and 2) required \> 30 mg per day prednisone for over 1 month or another therapy such as methotrexate (MTX) for treatment of myositis. Additionally, any adverse event reported as myositis was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Number of participants who experienced any event of myositis that occurred from randomization to Month 54 post-randomization. Documented myositis occurred if the participant had 1) elevated creatine phosphokinase (CPK), electromyography, and/or biopsy and 2) required \> 30 mg per day prednisone for over 1 month or another therapy such as methotrexate (MTX) for treatment of myositis. Additionally, any adverse event reported as myositis was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.

Time frame: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.

Time frame: 48 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in diffusion in liters of carbon monoxide (DLCO) % predicted or \>20% in forced vital capacity (FVC) % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted ), renal failure (chronic dialysis \> 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction \<30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).

Time frame: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted ), renal failure (chronic dialysis \> 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction \<30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).

Time frame: 48 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted ), renal failure (chronic dialysis \> 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction \<30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Infectious complications include any events that code to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class of Infections and infestations or events that a site has classified as an infectious event. These can include bacteremia, septicemia, fungemia, fever associated with infection, infectious pneumonia, idiopathic pneumonia syndrome, clinical infection (i.e. infection diagnosed with clinical features without identification of an organism) and other local/organ site-specific infections.

Time frame: Randomization through end of study follow-up (up to Month 72 post-randomization).

Population: Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.

Initiation of disease-modifying antirheumatic drugs (DMARDs). Participants were not expected to receive additional disease-modifying therapy for systemic sclerosis (SSc) in the absence of disease progression. In general, this includes the administration of any therapy clearly given for the purpose of treating the underlying SSc. It does not include concomitant treatments permitted in the protocol, such as use of methotrexate (15 g or less), anti-malarials, or minocycline for arthritis only. Systemic corticosteroids given at \> 10 mg/day (prednisone or prednisone equivalent), without clearly defined non-SSc indications, and methotrexate given for non-arthritis indications are examples of qualifying DMARDs.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Initiation of disease-modifying antirheumatic drugs (DMARDs). Participants were not expected to receive additional disease-modifying therapy for systemic sclerosis (SSc) in the absence of disease progression. In general, this includes the administration of any therapy clearly given for the purpose of treating the underlying SSc. It does not include concomitant treatments permitted in the protocol, such as use of methotrexate (15 g or less), anti-malarials, or minocycline for arthritis only. Systemic corticosteroids given at \> 10 mg/day (prednisone or prednisone equivalent), without clearly defined non-SSc indications, and methotrexate given for non-arthritis indications are examples of qualifying DMARDs.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for \>= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening was defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication, or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for \>= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for \>= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening will be defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for \>= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure \> 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure \> 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization was done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was \> 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure \> 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure \> 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization would be done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was \> 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Infectious complications include any events that code to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class of Infections and infestations or events that a site has classified as an infectious event. These can include bacteremia, septicemia, fungemia, fever associated with infection, infectious pneumonia, idiopathic pneumonia syndrome, clinical infection (i.e. infection diagnosed with clinical features without identification of an organism) and other local/organ site-specific infections.

Time frame: Randomization through end of study follow-up (up to Month 72 post-randomization).

Population: Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.

Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.

Time frame: Randomization through end of study follow-up (up to Month 72 post-randomization).

Population: Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.

Documented scleroderma renal crisis (hypertensive or non-hypertensive) occurring from randomization to Month 54 post-randomization was summarized. A hypertensive scleroderma renal crisis occurred if a participant obtained both of the following: New-onset hypertension, defined as systolic blood pressure (SBP) \>= 140 mmHg, diastolic blood pressure (DBP) \>= 90 mmHg, a rise in SBP \>= 30 mmHg compared to baseline, or a rise in DBP \>= 20 mmHg compared to baseline, and one of the following features: 1) increase of \>= 50 % above baseline in serum creatinine, 2) proteinuria (\>= 2+ by dipstick confirmed by protein:creatinine ratio \> 2.5), 3) hematuria (\>= 2+ by dipstick or \> 10 RBCs/HPF, without menstruation), 4) thrombocytopenia (\< 100,000 plts/mm3), or 5) hemolysis (determined by blood smear or increased reticulocyte count). Additionally, any adverse event reported as a scleroderma renal crisis was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Documented scleroderma renal crisis (hypertensive or non-hypertensive) occurring from randomization to Month 54 post-randomization was summarized. A hypertensive scleroderma renal crisis occurred if a participant obtained both of the following: New-onset hypertension, defined as systolic blood pressure (SBP) \>= 140 mmHg, diastolic blood pressure (DBP) \>= 90 mmHg, a rise in SBP \>= 30 mmHg compared to baseline, or a rise in DBP \>= 20 mmHg compared to baseline, and one of the following features: 1) increase of \>= 50 % above baseline in serum creatinine, 2) proteinuria (\>= 2+ by dipstick confirmed by protein:creatinine ratio \> 2.5), 3) hematuria (\>= 2+ by dipstick or \> 10 RBCs/HPF, without menstruation), 4) thrombocytopenia (\< 100,000 plts/mm3), or 5) hemolysis (determined by blood smear or increased reticulocyte count). Additionally, any adverse event reported as a scleroderma renal crisis was included in the analysis.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.

Time frame: Randomization through end of study follow-up (up to Month 72 post-randomization)

Population: Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.

Time to absolute neutrophil count (ANC) engraftment is defined as the number of days post-transplant until required levels of ANC are attained (for the mHSCT arm only). If engraftment did not occur within 28 days post-transplant, then the variable was set to 28 days. ANC engraftment required an ANC of \> 500 cells/microliter, maintained for 3 consecutive days.

Time frame: 28 days post-transplant

Population: Per-protocol (PP) - mHSCT arm only. The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm.

Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Time frame: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Time frame: 48 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Time frame: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Time frame: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.