Allogeneic Transplantation For Severe Osteopetrosis

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00775931
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research is to explore what we believe may be a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors.

Condition or Disease	Intervention/Treatment	Phase
Severe Osteopetrosis	Procedure: umbilical cord blood transplantation; Drug: Campath-1H; Radiation: Total Lymphoid Irradiation; Drug: Cyclophosphamide; Drug: Busulfan; Drug: Fludarabine monophosphate; Procedure: marrow graft transplantation	Phase 2/Phase 3

Detailed Description

This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: marrow graft transplant conditioning Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.	Drug: Campath-1H; Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.; Other Names: Alemtuzumab ; Radiation: Total Lymphoid Irradiation; Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).; Other Names: TLI ; Drug: Busulfan; patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.; Other Names: Busulfex ; Drug: Fludarabine monophosphate; Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.; Other Names: Fludara ; Procedure: marrow graft transplantation; Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.; Other Names: HSCT
Active Comparator: cord blood transplant conditioning Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.	Procedure: umbilical cord blood transplantation; Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.; Other Names: UCBT ; Drug: Campath-1H; Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.; Other Names: Alemtuzumab ; Drug: Cyclophosphamide; Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.; Other Names: Cytoxan ; Drug: Busulfan; patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.; Other Names: Busulfex

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Achieved Donor Cell Engraftment [Day 100]

Secondary Outcome Measures

1. Transplant Related Mortality at 100 Days [day 100]

2. Transplant Related Toxicity [Day 100 post transplant]

3. Incidence of Grade II - IV Acute Graft-versus-host Disease [by Day 100 after transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Day to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.

1. Bones that are uniformly markedly dense based on skeletal survey

2. No history that would suggest autosomal dominant inheritance

3. Evidence of hematologic changes that are attributed to the underlying disease, including

• the need for ongoing transfusions, OR

• the presence of progressive anemia or thrombocytopenia, OR

• a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR

• persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.

Exclusion Criteria:

• Patients >45 years of age

• Evidence of hepatic failure

• Pulmonary dysfunction sufficient to significantly increase the risk of transplant.

• Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.

• Cardiac compromise sufficient to substantially increase the risk of transplantation

• Severe, stable neurologic impairment.

• Human immunodeficiency virus (HIV) positivity.

• Pregnant or lactating females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of MInnesota, Fairview	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Paul Orchard, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00775931
• Other Study ID Numbers: MT2008-20; 0808M42261
• First Posted: Oct 20, 2008
• Last Update Posted: Jul 31, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Masonic Cancer Center, University of Minnesota: osteopetrosis
• Additional relevant MeSH terms: Osteopetrosis; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Alemtuzumab

Study Results

Participant Flow

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
Period Title: Overall Study
STARTED	6	1
COMPLETED	6	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning	Total
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving	Total of all reporting groups
Overall Participants	6	1	7
Age (Count of Participants)
<=18 years	4 66.7%	0 0%	4 57.1%
Between 18 and 65 years	2 33.3%	1 100%	3 42.9%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 33.3%	0 0%	2 28.6%
Male	4 66.7%	1 100%	5 71.4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Achieved Donor Cell Engraftment
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
Measure Participants	6	1
Count of Participants [Participants]	5 83.3%	0 0%

2. Secondary Outcome

Title	Transplant Related Mortality at 100 Days
Time Frame	day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
Measure Participants	6	1
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Transplant Related Toxicity
Time Frame	Day 100 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
Measure Participants	6	1
Count of Participants [Participants]	3 50%	1 100%

4. Secondary Outcome

Title	Incidence of Grade II - IV Acute Graft-versus-host Disease
Time Frame	by Day 100 after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Graft Transplant Conditioning	Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.	Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
Measure Participants	6	1
Count of Participants [Participants]	2 33.3%	0 0%

Adverse Events

Arm/Group Title	Marrow Graft Transplant Conditioning		Cord Blood Transplant Conditioning
Arm/Group Description	Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Fludarabine monophosphate: Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.		Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving
All Cause Mortality
	Marrow Graft Transplant Conditioning		Cord Blood Transplant Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Marrow Graft Transplant Conditioning		Cord Blood Transplant Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		0/1 (0%)
Cardiac disorders
Myocarditis	1/6 (16.7%)		0/1 (0%)
General disorders
Multi-Organ Failure	1/6 (16.7%)		0/1 (0%)
Acute Graft versus Host Disease	1/6 (16.7%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Marrow Graft Transplant Conditioning		Cord Blood Transplant Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Autoimmune Hemolytic Anemia	1/6 (16.7%)		0/1 (0%)
Blood Clot in Bladder Wall	0/6 (0%)		1/1 (100%)
Large Splenic Infarct	0/6 (0%)		1/1 (100%)
Cardiac disorders
Complete Heart Block	1/6 (16.7%)		0/1 (0%)
Pericardial Effusion	5/6 (83.3%)		1/1 (100%)
Placement of Epicardial Ventricular Pacing Wire	1/6 (16.7%)		0/1 (0%)
Eye disorders
Papilledema and Retinal Hemorrhages Leading to Blindness	1/6 (16.7%)		0/1 (0%)
Subconjunctival Hemorrhages	1/6 (16.7%)		0/1 (0%)
Gastrointestinal disorders
Partial Small Bowel Obstruction	1/6 (16.7%)		0/1 (0%)
Small Bowel Ascites	0/6 (0%)		1/1 (100%)
Infections and infestations
Acute Sinusitis	0/6 (0%)		1/1 (100%)
Bacterial Infection, Blood	4/6 (66.7%)		0/1 (0%)
Bacterial Infection, Respiratory	1/6 (16.7%)		1/1 (100%)
Bacterial Infection, Feces	1/6 (16.7%)		1/1 (100%)
Cystitis	2/6 (33.3%)		0/1 (0%)
Fungal Infection, Blood	2/6 (33.3%)		0/1 (0%)
Fungal Infection, Respiratory	3/6 (50%)		1/1 (100%)
Fungal Infection, Feces	0/6 (0%)		1/1 (100%)
Fungal Infection, Urine	1/6 (16.7%)		0/1 (0%)
Sinus Infection	1/6 (16.7%)		0/1 (0%)
Upper Respiratory Infection	1/6 (16.7%)		0/1 (0%)
Viral Infection, Blood	2/6 (33.3%)		1/1 (100%)
Viral Infection, Myocardium	1/6 (16.7%)		0/1 (0%)
Metabolism and nutrition disorders
Hyperglycemia	1/6 (16.7%)		0/1 (0%)
Nervous system disorders
Further Decompression of Lateral and Third Ventricles	1/6 (16.7%)		0/1 (0%)
Intracranial Hemorrhage	1/6 (16.7%)		0/1 (0%)
Intraparenchymal Bleed	1/6 (16.7%)		0/1 (0%)
Posterior Reversible Encephalopathy Syndrome	1/6 (16.7%)		0/1 (0%)
Seizure	1/6 (16.7%)		0/1 (0%)
Renal and urinary disorders
Requires Continuous Veno-Venous Hemofiltration, NOS	1/6 (16.7%)		0/1 (0%)
Requires Hemodialysis, NOS	1/6 (16.7%)		1/1 (100%)
Hyperechogenic Renomegaly with Ascites	0/6 (0%)		1/1 (100%)
Renal Failure	1/6 (16.7%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	2/6 (33.3%)		0/1 (0%)
Atelectasis	0/6 (0%)		1/1 (100%)
Requires Intubation, NOS	5/6 (83.3%)		1/1 (100%)
Low Lung Volumes	0/6 (0%)		1/1 (100%)
Pneumonia	5/6 (83.3%)		1/1 (100%)
Pulmonary Hemorrhage	1/6 (16.7%)		1/1 (100%)
Pulmonary Hypertension	1/6 (16.7%)		0/1 (0%)
Reactive Airway Disease	1/6 (16.7%)		0/1 (0%)
Respiratory Failure	2/6 (33.3%)		0/1 (0%)
Vascular disorders
Capillary Leak	1/6 (16.7%)		0/1 (0%)
Hypertension	1/6 (16.7%)		0/1 (0%)
Obstruction of Left Proximal Internal Jugular Vein	1/6 (16.7%)		0/1 (0%)

Limitations/Caveats

Because the disease being treated on this study is rare, our intent was to only report these outcomes in context with other protocols. At some point in the future if we have enough patients we will analyze the data.

More Information

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.