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High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study

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ClinicalTrials.gov Identifier: NCT00288626
Recruitment Status : Completed
First Posted : February 8, 2006
Results First Posted : April 4, 2017
Last Update Posted : September 19, 2017
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: Granulocyte-colony stimulating factor (G-CSF) and prednisone
Drug: Carmustine, etoposide, cytarabine, and melphalan (BEAM)
Procedure: Autologous hematopoietic stem cell transplant
Enrollment 25
Recruitment Details 36 participants were screened and 25 of those participants were enrolled at 3 sites in the US between August 2006 and August 2009. 24 participants were transplanted with the cellular product between February 2007 and April 2010
Pre-assignment Details  
Arm/Group Title HDIT and HCT
Hide Arm/Group Description Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥ 2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Period Title: Overall Study
Started 24
Completed 17
Not Completed 7
Reason Not Completed
Death             3
Withdrawal by Subject             4
Arm/Group Title HDIT and HCT
Hide Arm/Group Description Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT)and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
36.5  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
16
  66.7%
Male
8
  33.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
23
  95.8%
Unknown or Not Reported
1
   4.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
23
  95.8%
More than one race
1
   4.2%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
Expanded Disability Status Scale (EDSS) at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 24 participants
4.4  (.64)
[1]
Measure Description: Kurtzke’s Expanded Disability Status Scale (EDSS) assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS).
Number of Gadolinium-Enhanced Lesions at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Lesions per scan
Number Analyzed 24 participants
2.3  (5.8)
[1]
Measure Description: Multiple sclerosis disease-related lesions were assessed by gadolinium-enhanced magnetic resonance imaging (MRI). More lesions indicate more severe disease.
T1 Lesion Volume at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliliters
Number Analyzed 24 participants
1.2  (2.7)
[1]
Measure Description: A T1-weighted magnetic resonance imaging (MRI) scan assessed the volume of T1 lesions.
T2 Lesion Volume at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliliters
Number Analyzed 24 participants
11.1  (13.7)
[1]
Measure Description: A T2-weighted magnetic resonance imaging (MRI) scan assessed the volume of T2 lesions in the brain.
Normalized Brain Volume at Screening   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 24 participants
1.6  (0.1)
[1]
Measure Description: Magnetic resonance imaging (MRI) scan techniques measured ventricular volumes and grey and white matter brain volumes
1.Primary Outcome
Title Event-Free Survival Probability During the 5 Years After Transplant
Hide Description Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood’s formula for standard error.
Time Frame 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT).
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
0.692
(0.502 to 0.821)
2.Secondary Outcome
Title Event-Free Survival Probability During the 3 Years After Transplant
Hide Description Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood’s formula for standard error.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT).
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants received Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
0.784
(0.601 to 0.890)
3.Secondary Outcome
Title Survival From Treatment-Related Mortality
Hide Description The probability that a participant did not experienced a treatment-related death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood’s formula for standard error was used to calculate 90% confidence intervals. Participants that did not experience a treatment-related death were censored at the time of last follow-up. A treatment-related death was defined as death that occurred at any time after study entry and that was possibly, probably, or definitely related to the cellular product or possibly, probably, or definitely related to mobilization of autologous peripheral blood hematopoietic progenitor cells with G-CSF and prednisone or to the high-dose immunosuppressive therapy. There were no treatment-related mortality events in the study.
Time Frame From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT).
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥ 2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
1.0
(1.0 to 1.0)
2 Years Post Transplant
1.0
(1.0 to 1.0)
3 Years Post Transplant
1.0
(1.0 to 1.0)
4 Years Post Transplant
1.0
(1.0 to 1.0)
5 Years Post Transplant
1.0
(1.0 to 1.0)
4.Secondary Outcome
Title Overall Survival
Hide Description The probability that a participant did not experienced a death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood’s formula for standard error was used to calculate 90% confidence intervals. Participants that did not die were censored at the time of last follow-up.
Time Frame From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
1.0
(1.0 to 1.0)
2 Years Post Transplant
1.0
(1.0 to 1.0)
3 Years Post Transplant
0.957
(0.794 to 0.991)
4 Years Post Transplant
0.911
(0.742 to 0.971)
5 Years Post Transplant
0.863
(0.683 to 0.945)
5.Secondary Outcome
Title Survival From MS-Related Mortality
Hide Description The probability that a participant did not experienced a MS-related death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood’s formula for standard error was used to calculate 90% confidence intervals. Participants that did not experience a MS-related death were censored at the time of last follow-up. A MS-related death was defined as death that occurred at any time after study entry and that was possibly, probably, or definitely related to disease progression.
Time Frame From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
1.0
(1.0 to 1.0)
2 Years Post Transplant
1.0
(1.0 to 1.0)
3 Years Post Transplant
0.957
(0.794 to 0.991)
4 Years Post Transplant
0.957
(0.794 to 0.991)
5 Years Post Transplant
0.906
(0.728 to 0.970)
6.Secondary Outcome
Title Percent of Participants Who Experienced All-Cause Morbidity
Hide Description Morbidity is the occurrence of NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 adverse event grade 3 or higher.
Time Frame From the time of enrollment until completion of the 5-year follow-up, an average of 6 years.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
100
7.Secondary Outcome
Title Percent of Participants Who Experienced All-Cause Morbidity Within 12 Months of Post-HCT
Hide Description Morbidity is the occurrence of NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 adverse event grade 3 or higher.
Time Frame From the time of Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) to 1 year after HCT.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT).
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: Percentage of Participants
95.8
8.Secondary Outcome
Title Time to Neutrophil Engraftment
Hide Description Neutrophil engraftment, or neutrophil count recovery, is defined as an Absolute Neutrophil Count (ANC) > 500/ μL for 2 consecutive measurements on different days. Normal range is 1500 to 8000/μL. Reference: http://www.medicinenet.com
Time Frame From time of graft infusion to time of engraftment, up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: Days
10.8  (1.1)
9.Secondary Outcome
Title Time to Platelet Engraftment
Hide Description Platelet engraftment, or platelet count recovery, is defined as Platelets > 20,000/μL for two consecutive measurements on different days with no platelet transfusions in the preceding 7 days. Normal range is 150,000-450,000/μL. Reference: http://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/centers_excellence/womens_cardiovascular_health_center/patient_information/health_topics/platelets.html.
Time Frame From time of graft infusion to time of engraftment, up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: Days
18.5  (3.4)
10.Secondary Outcome
Title Event-Free Survival Probability After Transplant
Hide Description Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood’s formula for standard error.
Time Frame 1, 2, and 4 years after HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
0.958
(0.802 to 0.992)
2 Years Post Transplant
0.828
(0.650 to 0.920)
4 Years Post Transplant
0.738
(0.550 to 0.857)
11.Secondary Outcome
Title MS Progression-Free Survival Probability After Transplant
Hide Description

MS progression is measured as number of days from transplant to first Kurtzke’s Expanded Disability Status Scale (EDSS) increase of more than 0.5 relative to the baseline measurement. EDSS assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS).

Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood’s formula for standard error.

Time Frame 1 to 5 years after HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
1.0
(1.0 to 1.0)
2 Years Post Transplant
0.913
(0.747 to 0.972)
3 Years Post Transplant
0.913
(0.747 to 0.972)
4 Years Post Transplant
0.913
(0.747 to 0.972)
5 Years Post Transplant
0.913
(0.747 to 0.972)
12.Secondary Outcome
Title MRI Activity-Free Survival Probability After Transplant
Hide Description MS disease activity is measured as days from transplant to first occurrence of >= 2 new MS lesions on Magnetic resonance imaging (MRI) relative to baseline. Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood’s formula for standard error.
Time Frame 1 to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
0.958
(0.802 to 0.992)
2 Years Post Transplant
0.958
(0.802 to 0.992)
3 Years Post Transplant
0.958
(0.802 to 0.992)
4 Years Post Transplant
0.910
(0.739 to 0.971)
5 Years Post Transplant
0.863
(0.681 to 0.945)
13.Secondary Outcome
Title MS Relapse-Free Survival Probability After Transplant
Hide Description

MS clinical relapse is defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit or disability, and lasting over 48 hours. Clinical relapse was determined by the participant’s neurologist and was measured as days from transplant to new or worsening neurological symptom relative to baseline.

Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood’s formula for standard error.

Time Frame 1 to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
0.958
(0.802 to 0.992)
2 Years Post Transplant
0.915
(0.752 to 0.973)
3 Years Post Transplant
0.869
(0.695 to 0.947)
4 Years Post Transplant
0.869
(0.695 to 0.947)
5 Years Post Transplant
0.869
(0.695 to 0.947)
14.Secondary Outcome
Title Disease-Modifying Therapy Survival Probability After Transplant
Hide Description Treatment with disease-modifying therapy was measured by the number of days from transplant to the first treatment with an additional disease-modifying therapy. Examples of therapy include interferon beta-1a, glatiramer acetate, natalizumab, alemtuzumab, other immunosuppressive medications, or experimental therapies directed against MS activity. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood’s formula for standard error.
Time Frame 1 to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Probability
1 Year Post Transplant
1.0
(1.0 to 1.0)
2 Years Post Transplant
1.0
(1.0 to 1.0)
3 Years Post Transplant
1.0
(1.0 to 1.0)
4 Years Post Transplant
1.0
(1.0 to 1.0)
5 Years Post Transplant
0.950
(0.767 to 0.990)
15.Secondary Outcome
Title Change From Baseline in Extended Disability Status Scale (EDSS)
Hide Description Kurtzke’s Expanded Disability Status Scale (EDSS) assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS). Change from baseline was computed as the value at the time point minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening. A change of > 0.5 in EDSS was a treatment-failure criterion.
Time Frame 6 months to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
6 Months Post Transplant -0.3  (1.0)
1 Year Post Transplant -0.7  (0.9)
2 Years Post Transplant -0.8  (1.1)
3 Years Post Transplant -0.8  (1.1)
4 Years Post Transplant -0.6  (1.2)
5 Years Post Transplant -0.9  (1.0)
16.Secondary Outcome
Title Change From Baseline in Number of Gadolinium-Enhanced Lesions
Hide Description Multiple sclerosis disease-related lesions were assessed by gadolinium-enhanced magnetic resonance imaging (MRI). Change from baseline was computed as the value at the time point minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening.
Time Frame 8 weeks to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: Lesions per scan
8 Weeks Post Transplant -2.1  (4.9)
6 Months Post Transplant -2.3  (6.0)
1 Year Post Transplant -2.5  (6.1)
2 Years Post Transplant -2.5  (6.1)
3 Years Post Transplant -1.3  (2.2)
4 Years Post Transplant -2.2  (6.7)
5 Years Post Transplant -2.7  (7.0)
17.Secondary Outcome
Title Number of New T2-Weighted Lesions From Baseline
Hide Description A T2-weighted magnetic resonance imaging (MRI) scan was used to determine the number of new T2 lesions in the brain relative to Baseline. A value of 0 means that the participant didn’t worsen. Values greater than 0 indicate an increase in disease activity from baseline.
Time Frame 6 Months to 5 years after HCT
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Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: Lesions per scan
6 Months Post Transplant 0.2  (0.5)
1 Year Post Transplant 0.2  (0.5)
2 Years Post Transplant 0.2  (0.5)
3 Years Post Transplant 0.1  (0.3)
4 Years Post Transplant 0.4  (1.2)
5 Years Post Transplant 0.1  (0.3)
18.Secondary Outcome
Title Change From Baseline in T2-Weighted Lesion Volume
Hide Description A T2-weighted magnetic resonance imaging (MRI) scan was used to assess the volume of T2 lesions in the brain. Change from baseline was computed as the value at the time point minus the baseline value.
Time Frame 8 weeks to 5 years after HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: milliliters
8 Weeks Post Transplant -0.8  (1.9)
6 Months Post Transplant -0.7  (1.5)
1 Year Post Transplant -1.0  (1.6)
2 Years Post Transplant -1.6  (3.0)
3 Years Post Transplant -1.9  (3.1)
4 Years Post Transplant -1.9  (3.2)
5 Years Post Transplant -2.3  (3.6)
19.Secondary Outcome
Title Change From Baseline in T1-Weighted Lesion Volume
Hide Description A T1-weighted magnetic resonance imaging (MRI) scan was used to assess the volume of T1 lesions in the brain. Change from baseline was computed as the value at the time point minus the baseline value.
Time Frame 8 weeks to 5 years after HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: milliliter
8 Weeks Post Transplant -0.1  (0.4)
6 Months Post Transplant 0.0  (0.4)
1 Year Post Transplant 0.2  (0.4)
2 Years Post Transplant 0.3  (0.7)
3 Years Post Transplant 0.4  (0.6)
4 Years Post Transplant 0.4  (0.7)
5 Years Post Transplant 0.3  (0.7)
20.Secondary Outcome
Title Percent Change From Screening in Brain Volume
Hide Description Magnetic resonance imaging (MRI) scan techniques measured ventricular volumes and grey and white matter brain volumes. Change from screening was computed as the value at the time point minus the screening value.
Time Frame 8 weeks to 5 years after HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received High-Dose Immunosuppressive Therapy (HDIT) and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT)
Arm/Group Title HDIT and HCT
Hide Arm/Group Description:
Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until ≥2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to >500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: Percent Change
8 Weeks Post Transplant -0.8  (0.8)
6 Months Post Transplant -1.1  (0.9)
1 Year Post Transplant -1.2  (1.1)
2 Years Post Transplant -1.6  (1.4)
3 Years Post Transplant -2.2  (1.4)
4 Years Post Transplant -2.0  (1.4)
5 Years Post Transplant -2.3  (1.6)
Time Frame From the time the participant signed informed consent until the participant completed the 5-year follow-up, an average of 6 years
Adverse Event Reporting Description Adverse events were reported for all participants enrolled. One participant in the group did not receive a transplant and was followed for safety only, no other analyses were performed for this participant.
 
Arm/Group Title HDIT and HCT
Hide Arm/Group Description Participants recv'd Granulocyte Colony Stimulating Factor (G-CSF) by injection for 4-5 days to increase the number of blood stem cells in the blood stream by mobilizing them from the bone marrow. Leukapheresis was performed until > 2.0 x 10^6 CD34+ hematopoietic progenitor cells (HPCs) per kg were collected and frozen for future use. After ≥7 days following the last G-CSF dose, patients were hospitalized and received high-dose immunosuppression (HDIT) and immunosuppressive agent thymoglobulin 2.5 mg/kg over the course of 6 days. HDIT consisted of carmustine 300mg/m^2, etoposide 200 mg/m^2 cytarabine 200 mg/m^2, and melphalan 140 mg/m^2. CD34+ HPCs were thawed and infused according to institutional best practice for blood component transfusion over approximately 30 minutes. Patients were hospitalized until recovery of ANC to > 500/uL for at least 2 days. Prednisone was administered (0.5 mg/kg/day) from Days 7 to 21 after HCT and tapered over 2 weeks to prevent engraftment syndrome.
All-Cause Mortality
HDIT and HCT
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
HDIT and HCT
Affected / at Risk (%) # Events
Total   16/25 (64.00%)    
Blood and lymphatic system disorders   
Leukopenia  1  2/25 (8.00%)  3
Lymphopenia  1  3/25 (12.00%)  3
Cardiac disorders   
Atrioventricular block  1  1/25 (4.00%)  1
Cardio-respiratory arrest  1  1/25 (4.00%)  1
Congenital, familial and genetic disorders   
Arteriovenous malformation  1  1/25 (4.00%)  1
Eye disorders   
Vision blurred  1  1/25 (4.00%)  1
Gastrointestinal disorders   
Constipation  1  1/25 (4.00%)  1
General disorders   
Chest pain  1  1/25 (4.00%)  1
Fatigue  1  1/25 (4.00%)  1
Pyrexia  1  2/25 (8.00%)  4
Hepatobiliary disorders   
Gallbladder obstruction  1  1/25 (4.00%)  1
Immune system disorders   
Engraftment syndrome  1  1/25 (4.00%)  1
Infections and infestations   
Acinetobacter infection  1  1/25 (4.00%)  1
Bacteraemia  1  1/25 (4.00%)  1
Cellulitis  1  1/25 (4.00%)  1
Chronic sinusitis  1  1/25 (4.00%)  1
Epstein-Barr virus infection  1  1/25 (4.00%)  1
Meningitis aseptic  1  1/25 (4.00%)  1
Pneumonia  1  1/25 (4.00%)  2
Sepsis  1  1/25 (4.00%)  1
Urinary tract infection  1  1/25 (4.00%)  2
Investigations   
Alanine aminotransferase increased  1  1/25 (4.00%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/25 (4.00%)  1
Hyperuricaemia  1  1/25 (4.00%)  1
Hypokalaemia  1  2/25 (8.00%)  2
Musculoskeletal and connective tissue disorders   
Back pain  1  1/25 (4.00%)  1
Pain in extremity  1  2/25 (8.00%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer in situ  1  1/25 (4.00%)  1
Nervous system disorders   
Anoxic encephalopathy  1  1/25 (4.00%)  1
Headache  1  1/25 (4.00%)  1
Hemiparesis  1  2/25 (8.00%)  2
Motor dysfunction  1  1/25 (4.00%)  1
Multiple sclerosis  1  3/25 (12.00%)  3
Neurological symptom  1  1/25 (4.00%)  1
Pregnancy, puerperium and perinatal conditions   
Pregnancy  1  1/25 (4.00%)  1
Psychiatric disorders   
Depression  1  1/25 (4.00%)  2
Mania  1  1/25 (4.00%)  1
Suicide attempt  1  2/25 (8.00%)  2
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/25 (4.00%)  3
Dyspnoea  1  1/25 (4.00%)  1
Pneumonitis  1  1/25 (4.00%)  2
Pulmonary embolism  1  2/25 (8.00%)  2
Respiratory arrest  1  1/25 (4.00%)  1
Respiratory failure  1  1/25 (4.00%)  1
Vascular disorders   
Deep vein thrombosis  1  1/25 (4.00%)  1
Jugular vein thrombosis  1  1/25 (4.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HDIT and HCT
Affected / at Risk (%) # Events
Total   25/25 (100.00%)    
Blood and lymphatic system disorders   
Anaemia  1  4/25 (16.00%)  5
Febrile neutropenia  1  2/25 (8.00%)  2
Leukopenia  1  22/25 (88.00%)  31
Lymphopenia  1  25/25 (100.00%)  48
Neutropenia  1  23/25 (92.00%)  27
Thrombocytopenia  1  19/25 (76.00%)  25
Endocrine disorders   
Hypothyroidism  1  2/25 (8.00%)  2
Gastrointestinal disorders   
Abdominal pain  1  2/25 (8.00%)  2
Diarrhoea  1  5/25 (20.00%)  5
Gastritis  1  2/25 (8.00%)  2
Nausea  1  10/25 (40.00%)  10
General disorders   
Chest pain  1  2/25 (8.00%)  2
Infections and infestations   
Bacteraemia  1  3/25 (12.00%)  5
Bronchitis  1  2/25 (8.00%)  2
Catheter site infection  1  2/25 (8.00%)  2
Cytomegalovirus infection  1  6/25 (24.00%)  6
Herpes zoster  1  7/25 (28.00%)  8
Infection  1  2/25 (8.00%)  2
Influenza  1  2/25 (8.00%)  2
Pharyngitis  1  2/25 (8.00%)  2
Sinusitis  1  5/25 (20.00%)  7
Upper respiratory tract infection  1  5/25 (20.00%)  9
Urinary tract infection  1  7/25 (28.00%)  12
Injury, poisoning and procedural complications   
Radius fracture  1  2/25 (8.00%)  3
Investigations   
Alanine aminotransferase increased  1  5/25 (20.00%)  6
Metabolism and nutrition disorders   
Hyperglycaemia  1  4/25 (16.00%)  5
Musculoskeletal and connective tissue disorders   
Neck pain  1  2/25 (8.00%)  2
Osteopenia  1  2/25 (8.00%)  2
Nervous system disorders   
Headache  1  3/25 (12.00%)  6
Multiple sclerosis  1  2/25 (8.00%)  2
Peripheral sensory neuropathy  1  2/25 (8.00%)  2
Skin and subcutaneous tissue disorders   
Rash  1  4/25 (16.00%)  4
Vascular disorders   
Hypotension  1  2/25 (8.00%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.0
24 of the 25 planned transplants occurred. One of the enrolled participants developed adverse events that caused withdrawal from the study before the planned transplant.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
Phone: 301-594-7669
Publications of Results:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00288626     History of Changes
Other Study ID Numbers: DAIT ITN033AI
DAIT SCMS2
First Submitted: February 7, 2006
First Posted: February 8, 2006
Results First Submitted: December 6, 2016
Results First Posted: April 4, 2017
Last Update Posted: September 19, 2017