Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)

• Sponsor: HealthCore-NERI (Other)
• Overall Status: Completed
• CT.gov ID: NCT00627393
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 114
• Locations: 13
• Arms: 3
• Duration (Months): 61
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Neutropenia, a condition characterized by an abnormally low number of infection-fighting white blood cells called neutrophils, commonly develops in people who have undergone chemotherapy or hematopoietic stem cell (HSC) transplantation. The severely reduced immunity of those with neutropenia can put them at risk of entry of life-threatening infections, making the implementation of treatments that increase white blood cell numbers important. Several studies have shown that the transfusion of donor granulocytes, a type of white blood cell that includes neutrophils, is effective in promoting the recovery of adequate numbers of granulocytes. However, granulocyte transfusions can cause side effects, and it is not known whether the success of the therapy outweighs the health risks of the side effects. This study will evaluate the safety and effectiveness of granulocyte transfusions in treating people with a bacterial or fungal infection during neutropenia.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia; Infection	Drug: Standard antimicrobial therapy; Biological: Granulocyte transfusions; Drug: G-CSF/dexamethasone; Device: Apheresis machine	Phase 3

Detailed Description

Thousands of people each year are hospitalized for neutropenia, which continues to cause substantial morbidity and mortality for those affected. Neutropenia is primarily caused by chemotherapy and various other cancer treatments, such as radiation therapy, biotherapy, and HSC transplantation. Signs and symptoms of neutropenia may include high fever, chills, sore throat, and diarrhea. In neutropenia, the number of neutrophils, a type of granulocyte, is greatly reduced, weakening the body's immune system and increasing the risk of infection. Therefore, a method to provide adequate numbers of functional granulocytes to people with neutropenia could be of greatest benefit for recovery. Administration of a combination of two drugs, granulocyte colony-stimulating factor (G-CSF) and dexamethasone, has been show to stimulate the body to produce a large number of granulocytes. Granulocyte transfusions obtained from donors who have received these two drugs may help people with low white blood cell counts fight infections until their own white blood cell counts recover. However, it is not clear whether the benefits of granulocyte transfusions outweigh the risks of side effects. This study will compare the safety and effectiveness of granulocyte transfusions with standard antimicrobial therapy versus the safety and effectiveness of standard antimicrobial therapy alone in increasing granulocyte numbers and in improving survival rates in people with bacterial or fungal infection during neutropenia.

Participation in the research portion of this study will last about 3 months. All participants who were not previously receiving treatment with standard antimicrobial therapy will begin therapy immediately upon study entry. Participants will then be assigned randomly to receive either granulocyte transfusion plus continued antimicrobial therapy or continued antimicrobial therapy alone. All participants will be monitored for a maximum of 42 days, during which they will provide information on medical history and ongoing status of antimicrobial therapy. Daily blood samples to measure white blood cell count will be obtained from participants until samples show that participants are making their own granulocytes. Samples will then be collected weekly until Day 42. There may be additional blood draws depending on the type of infection present in participants.

Granulocyte transfusions will be given daily during the 42-day treatment period, depending on granulocyte donor availability. Blood counts will be checked immediately before and after each transfusion to measure granulocyte levels. Transfusions will be stopped if participants start making their own granulocytes, experience serious side effects, or show a reduction in infection. At Month 3 after study entry, follow-up information will be collected about all participants' health status through reviewing their medical records and contacting their physicians.

Participation for granulocyte donors will last 1 week from the time of donation. Community donors may provide more than one granulocyte donation, but no more than one donation every 3 days. Frequency of donation from a family member will be according to local blood bank criteria with approval from a blood bank physician. Both community donors and family donors are limited to eight donations each year. Twelve hours before each donation, participants will be injected with Neupogen, which contains G-CSF, and they will take one dose of dexamethasone by mouth. Participants will then undergo a blood draw, followed by a procedure using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours and will involve the drawing of blood from each arm, the separation of granulocytes from the red blood cells and plasma in the machine, and the return of the red blood cells and plasma to the participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: High Dose Granulocyte Transfusions for the Treatment of Infection in Neutropenia: The RING Study (Resolving Infection in Neutropenia With Granulocytes)
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Participants will receive granulocyte transfusions in addition to standard antimicrobial therapy	Drug: Standard antimicrobial therapy; Antimicrobial therapy is broadly defined as therapy within the standard of care for a particular infection and should be consistent within a given institution. Participants will undergo the recommended therapy for specific infections for 42 days.; Biological: Granulocyte transfusions; Participants will receive one granulocyte transfusion per day until one of the following occurs: recovery from neutropenia, life-threatening toxicity, resolution or improvement of infection, or Day 42 after treatment. Granulocyte content of each transfusion is targeted to be at least 4 x 10^10 per collection (or proportionately less for participants less than 30 kg in weight).
Active Comparator: 2 Participants will receive standard antimicrobial therapy alone	Drug: Standard antimicrobial therapy; Antimicrobial therapy is broadly defined as therapy within the standard of care for a particular infection and should be consistent within a given institution. Participants will undergo the recommended therapy for specific infections for 42 days.
Other: 3 Participants will donate granulocytes after receiving a combination of two drugs, G-CSF and dexamethasone	Drug: G-CSF/dexamethasone; Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth.; Other Names: Neupogen ; Device: Apheresis machine; Participants will undergo a procedure using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours and will involve the drawing of blood from each arm, the separation of granulocytes from the red cells and plasma in the machine, and the return of the red cells and plasma to the participants.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Are Alive at 42 Days After Treatment and Have Had Microbial Response [Measured at Day 42]

   Microbial response was defined as follows: A negative blood culture test at 42 days after randomization for subjects with fungemia (candidemia or fusariosis) or bacteremia. Improvement of signs and symptoms of infectious disease (complete or partial response) at 42 days after randomization.

Secondary Outcome Measures

1. Alloimmunization, Defined as the Appearance of Anti-human Leukocyte Antigen (HLA) or Antineutrophil Antibodies [Measured at Days 14 and 42]

2. Serious Granulocyte Transfusion Reactions, Including Febrile, Allergic, and Pulmonary Reactions (Transfusion Arm Only) [Measured within 6 hours after end of transfusion]

3. Graft Versus Host Disease Among Recipients of Allogeneic Stem Cell Transplantation [Measured at Day 42]

   Time to GVHD incidence between the two treatment groups was compared using Gray's model that takes into account death as a competing risk.

4. Overall Incidence of Adverse Effects [Measured through Day 42]

5. Fever Resolution [Measured through Day 42]

   Fever resolution between the two treatment groups was compared using Gray's model that takes into account death as a competing risk.

6. Time to Negative Test for Fungal Antigenemia (e.g., Galactomannan Antigenemia Among Participants With Invasive Aspergillosis) [Measured at Days 7, 14, and 42]

7. Time to Negative Blood Culture for Participants With Positive Blood Culture at Baseline [Measured through Day 42]

8. Long-term Survival [Measured at Month 3]

9. Serious Adverse Events in Granulocyte Donors [Measured at Week 1 after G-CSF administration]

10. Donor Availability (Proportion of Scheduled Granulocyte Transfusion Days on Which Granulocytes Were Available) [Measured through study completion]

11. Evaluation of Granulocyte Yield [Measured immediately after each granulocyte donation]

12. Discontinuation of Granulocyte Transfusions Due to Toxicity or Intolerance [Measured through Day 42]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Severe neutropenia (Absolute Neutrophil Count < 500/mm^3) due to marrow failure caused by underlying disease or therapy

• Must have one of the following: fungemia; bacteremia; proven or presumptive invasive tissue bacterial infection; or proven, probable, or presumptive invasive fungal infection

Exclusion Criteria:

• Unlikely to survive 5 days

• Evidence that patient will not be neutropenic at least 5 days

• Previously enrolled in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
2	Johns Hopkins Hospital	Baltimore	Maryland	United States	21267
3	Children's Hospital Boston	Boston	Massachusetts	United States	02115
4	University of Minnesota	Minneapolis	Minnesota	United States	55455
5	Montefiore Medical Center	Bronx	New York	United States	10461
6	Weill Medical College, Cornell University	New York	New York	United States	10021
7	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
8	Chlidren's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
9	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	University of Pittsburgh Presbyterian and Shadyside	Pittsburgh	Pennsylvania	United States	15213
11	University of Washington Medical Center	Seattle	Washington	United States	98195
12	University of Wisconsin at Madison	Madison	Wisconsin	United States	53792
13	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53201

Sponsors and Collaborators

• HealthCore-NERI
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Susan F. Assmann, PhD, HealthCore-NERI
• Principal Investigator: Jan McFarland, MD, Froedtert Hospital
• Principal Investigator: Eliot Williams, MD, University of Wisconsin, Madison
• Principal Investigator: Ellis Neufeld, MD, Children's Hospital Boston/Brigham and Women's Hospital
• Principal Investigator: James Bussel, MD, Weill Medical College, Cornell University
• Principal Investigator: Cassandra Josephson, MD, Emory University
• Principal Investigator: Paul Ness, MD, Johns Hopkins University
• Principal Investigator: Sherrill Slichter, MD, University of Washington
• Study Chair: Thomas Price, MD, Bloodworks
• Principal Investigator: Ronald Strauss, MD, University of Iowa
• Principal Investigator: Jeffrey McCullough, MD, University of Minnesota
• Principal Investigator: James George, MD, University of Oklahoma
• Principal Investigator: Bruce Sachais, MD, PHD, University of Pennsylvania
• Principal Investigator: David Friedman, MD, Children's Hospital of Philadelphia
• Principal Investigator: Darrell Triulzi, MD, University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: HealthCore-NERI
• ClinicalTrials.gov Identifier: NCT00627393
• Other Study ID Numbers: 557; U01HL072268; HL072268; HL072291; HL072196; HL072248; HL072191; HL072305; HL072028; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290
• First Posted: Mar 3, 2008
• Last Update Posted: Apr 17, 2015
• Last Verified: Apr 1, 2014

• Keywords provided by HealthCore-NERI: Granulocyte Transfusions
• Additional relevant MeSH terms: Infections; Communicable Diseases; Neutropenia; Anti-Infective Agents; Anti-Bacterial Agents; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Period Title: Intention-To-Treat Analysis
STARTED	58	56
COMPLETED	49	48
NOT COMPLETED	9	8
Period Title: Intention-To-Treat Analysis
STARTED	49	48
COMPLETED	39	35
NOT COMPLETED	10	13

Baseline Characteristics

Arm/Group Title	Control Arm	Granulocyte Arm	Total
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.	Total of all reporting groups
Overall Participants	58	56	114
Age (Count of Participants)
<=18 years	6 10.3%	4 7.1%	10 8.8%
Between 18 and 65 years	39 67.2%	32 57.1%	71 62.3%
>=65 years	13 22.4%	20 35.7%	33 28.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.1 (19.8)	54.8 (16.3)	51.9 (18.3)
Sex: Female, Male (Count of Participants)
Female	28 48.3%	23 41.1%	51 44.7%
Male	30 51.7%	33 58.9%	63 55.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 8.6%	1 1.8%	6 5.3%
Not Hispanic or Latino	40 69%	44 78.6%	84 73.7%
Unknown or Not Reported	13 22.4%	11 19.6%	24 21.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 6.9%	1 1.8%	5 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.7%	6 10.7%	7 6.1%
White	39 67.2%	40 71.4%	79 69.3%
More than one race	1 1.7%	0 0%	1 0.9%
Unknown or Not Reported	13 22.4%	9 16.1%	22 19.3%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	76.0 (23.8)	78.7 (20.6)	77.3 (22.2)
Cause of neutropenia (participants) [Number]
Chemotherapy only	43 74.1%	44 78.6%	87 76.3%
Infection	7 12.1%	3 5.4%	10 8.8%
HST (or preparation for HST)	8 13.8%	9 16.1%	17 14.9%
ANC prior to randomization (x10^9 cells/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [x10^9 cells/L]	0.046 (0.091)	0.058 (0.096)	0.052 (0.094)
Zubrod score (participants) [Number]
0 to 2	19 32.8%	18 32.1%	37 32.5%
3 to 5	39 67.2%	38 67.9%	77 67.5%
Infection type (participants) [Number]
Bacteremia only	16 27.6%	17 30.4%	33 28.9%
Tissue bacterial infection	15 25.9%	13 23.2%	28 24.6%
Fungemia only	8 13.8%	5 8.9%	13 11.4%
Tissue fungal infection	19 32.8%	21 37.5%	40 35.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Are Alive at 42 Days After Treatment and Have Had Microbial Response
Description	Microbial response was defined as follows: A negative blood culture test at 42 days after randomization for subjects with fungemia (candidemia or fusariosis) or bacteremia. Improvement of signs and symptoms of infectious disease (complete or partial response) at 42 days after randomization.
Time Frame	Measured at Day 42

Outcome Measure Data

Analysis Population Description

All adjudicated or deceased subjects in intention-to-treat analyses.

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	49	48
Number [percentage of participants]	42.9 74%	41.7 74.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Arm, Granulocyte Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Regression, Logistic
	Comments	Ordinary multiple logistic regression including treatment arm, infection strata, underlying disease, zubrod score, respiratory symptoms, and age.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.44 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Control group is the reference group. Model adjusted for infection strata, underlying disease, zubrod score, respiratory symptoms, and age.

2. Secondary Outcome

Title	Alloimmunization, Defined as the Appearance of Anti-human Leukocyte Antigen (HLA) or Antineutrophil Antibodies
Time Frame	Measured at Days 14 and 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Serious Granulocyte Transfusion Reactions, Including Febrile, Allergic, and Pulmonary Reactions (Transfusion Arm Only)
Time Frame	Measured within 6 hours after end of transfusion

Outcome Measure Data

Analysis Population Description

Subjects who received granulocyte transfusions. Six subjects in the control group received granulocyte transfusions in violation of the protocol.

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	6	51
No events reported	5 8.6%	19 33.9%
Grade 1	0 0%	7 12.5%
Grade 2	1 1.7%	14 25%
Grade 3	0 0%	10 17.9%
Grade 4	0 0%	1 1.8%

4. Secondary Outcome

Title	Graft Versus Host Disease Among Recipients of Allogeneic Stem Cell Transplantation
Description	Time to GVHD incidence between the two treatment groups was compared using Gray's model that takes into account death as a competing risk.
Time Frame	Measured at Day 42

Outcome Measure Data

Analysis Population Description

Subjects who had allogeneic stem cell transplantation

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	8	7
Number [proportion of subjects, GVHD incidnence]	0.67	0.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Arm, Granulocyte Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	Competing risks analysis for time to GVHD for subjects with allogeneic HST. The sample size was very small (n=7 in the granulocyte group, and n=8 in the control group).
	Method	Competing Risks
	Comments
Method of Estimation	Estimation Parameter	Log Rank P-Value
	Estimated Value	0.43
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Incidence of Adverse Effects
Time Frame	Measured through Day 42

Outcome Measure Data

Analysis Population Description

All randomized subjects.

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	58	56
0 Event	33 56.9%	30 53.6%
1 Event	21 36.2%	20 35.7%
2 Events	2 3.4%	5 8.9%
3 Events	1 1.7%	0 0%
6 Events	0 0%	1 1.8%
9 Events	1 1.7%	0 0%

6. Secondary Outcome

Title	Fever Resolution
Description	Fever resolution between the two treatment groups was compared using Gray's model that takes into account death as a competing risk.
Time Frame	Measured through Day 42

Outcome Measure Data

Analysis Population Description

Subjects who had fever at baseline.

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	53	47
Number [proportion of subjects, resolved fever]	0.89	0.94

7. Secondary Outcome

Title	Time to Negative Test for Fungal Antigenemia (e.g., Galactomannan Antigenemia Among Participants With Invasive Aspergillosis)
Time Frame	Measured at Days 7, 14, and 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Time to Negative Blood Culture for Participants With Positive Blood Culture at Baseline
Time Frame	Measured through Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Long-term Survival
Time Frame	Measured at Month 3

Outcome Measure Data

Analysis Population Description

All randomized subjects.

Arm/Group Title	Control Arm	Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	58	56
Number [participants]	30 51.7%	20 35.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Arm, Granulocyte Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Log Rank
	Comments	Log-rank test to compare survival distributions between the control group and treatment group.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.293
	Confidence Interval	(2-Sided) 95%; 0.778 to 2.147
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25885
	Estimation Comments	The control group is considered the reference group.

10. Secondary Outcome

Title	Serious Adverse Events in Granulocyte Donors
Time Frame	Measured at Week 1 after G-CSF administration

Outcome Measure Data

Analysis Population Description

237 subjects consented to G-CSF and dexamethasone administration prior to granulocyte donation.

Arm/Group Title	Granulocyte Donors
Arm/Group Description	Participants will donate granulocytes after receiving a combination of two drugs, G-CSF and dexamethasone G-CSF/dexamethasone: Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth. Apheresis machine: Participants will undergo a procedure using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours and will involve the drawing of blood from each arm, the separation of granulocytes from the red cells and plasma in the machine, and the return of the red cells and plasma to the participants.
Measure Participants	237
Myalgia and backpain of unexpected duration	1 1.7%
Abnormal nucleated red blood cell differential	1 1.7%

11. Secondary Outcome

Title	Donor Availability (Proportion of Scheduled Granulocyte Transfusion Days on Which Granulocytes Were Available)
Time Frame	Measured through study completion

Outcome Measure Data

Analysis Population Description

The unit of analysis is patient-days where a granulocyte transfusion was scheduled.

Arm/Group Title	Granulocyte Arm
Arm/Group Description	Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
Measure Participants	56
Measure Patient-days	543
Number [percentage of available granulocyte days]	62.62

12. Secondary Outcome

Title	Evaluation of Granulocyte Yield
Time Frame	Measured immediately after each granulocyte donation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Granulocyte Donors
Arm/Group Description	Participants will donate granulocytes after receiving a combination of two drugs, G-CSF and dexamethasone G-CSF/dexamethasone: Twelve hours before each donation, participants will be injected with G-CSF and will take one dose of dexamethasone by mouth. Apheresis machine: Participants will undergo a procedure using an apheresis machine for granulocyte collection. The procedure will last 3 to 4 hours and will involve the drawing of blood from each arm, the separation of granulocytes from the red cells and plasma in the machine, and the return of the red cells and plasma to the participants.
Measure Participants	237
Measure Granulocyte Donations	340
Median (Inter-Quartile Range) [Granulocyte Yield (billion cells/liter)]	174.75

13. Secondary Outcome

Title	Discontinuation of Granulocyte Transfusions Due to Toxicity or Intolerance
Time Frame	Measured through Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Serious adverse events were reported up to 42 days after randomization.
Adverse Event Reporting Description	Serious adverse events and other adverse events (i.e. granulocyte transfusion related events) data were collected. The number of participants at risk for other adverse events corresponds to the number of participants who received granulocyte transfusions (6 control arm subjects and 51 granulocyte arm subjects).
Arm/Group Title	Control Arm		Granulocyte Arm
Arm/Group Description	Received antimicrobial therapy alone.		Received G-CSF/dexamethasone-mobilized granulocyte transfusions in addition to antimicrobial therapy.
All Cause Mortality
	Control Arm		Granulocyte Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control Arm		Granulocyte Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/58 (43.1%)		26/56 (46.4%)
Blood and lymphatic system disorders
Activated partial thromboplastin time shortened	1/58 (1.7%)		0/56 (0%)
Anaemia	1/58 (1.7%)		0/56 (0%)
Increased blast cell count	1/58 (1.7%)		0/56 (0%)
Increased blood creatinine	1/58 (1.7%)		0/56 (0%)
Febrile neutropenia	1/58 (1.7%)		2/56 (3.6%)
Hydraemia	0/58 (0%)		1/56 (1.8%)
Hyperbilirubinaemia	1/58 (1.7%)		0/56 (0%)
Hypoalbuminaemia	1/58 (1.7%)		0/56 (0%)
Hypocalcaemia	1/58 (1.7%)		0/56 (0%)
Hypokalaemic syndrome	1/58 (1.7%)		0/56 (0%)
Increased prothrombin level	1/58 (1.7%)		0/56 (0%)
Sepsis syndrome	1/58 (1.7%)		2/56 (3.6%)
Cardiac disorders
Atrial fibrillation	1/58 (1.7%)		0/56 (0%)
Cardiomyopathy	1/58 (1.7%)		0/56 (0%)
Cardiopulmonary failure	1/58 (1.7%)		0/56 (0%)
Pericardial effusion	0/58 (0%)		1/56 (1.8%)
Gastrointestinal disorders
Abdominal symptom	0/58 (0%)		1/56 (1.8%)
Gastric haemorrhage	1/58 (1.7%)		0/56 (0%)
Nausea	0/58 (0%)		1/56 (1.8%)
Vomiting	0/58 (0%)		1/56 (1.8%)
General disorders
Chills	0/58 (0%)		1/56 (1.8%)
Encephalopathy	1/58 (1.7%)		0/56 (0%)
Fatigue	0/58 (0%)		1/56 (1.8%)
Hallucination	1/58 (1.7%)		0/56 (0%)
Hypotension	0/58 (0%)		2/56 (3.6%)
Multi-organ failure	4/58 (6.9%)		3/56 (5.4%)
Immune system disorders
Graft versus host disease	0/58 (0%)		1/56 (1.8%)
Infections and infestations
Abdominal infection	1/58 (1.7%)		0/56 (0%)
Abdominal sepsis	1/58 (1.7%)		2/56 (3.6%)
Cytomegalovirus viraemia	0/58 (0%)		1/56 (1.8%)
Febrile infection	1/58 (1.7%)		0/56 (0%)
Fungaemia	2/58 (3.4%)		1/56 (1.8%)
Infection in an immunocompromised host	1/58 (1.7%)		0/56 (0%)
Sepsis neonatal	1/58 (1.7%)		1/56 (1.8%)
Septic shock	1/58 (1.7%)		3/56 (5.4%)
Injury, poisoning and procedural complications
Acute lung injury	0/58 (0%)		1/56 (1.8%)
Metabolism and nutrition disorders
Metabolic disorder	1/58 (1.7%)		0/56 (0%)
Nervous system disorders
Ataxia	0/58 (0%)		1/56 (1.8%)
Psychiatric disorders
Mental status changes	1/58 (1.7%)		1/56 (1.8%)
Reproductive system and breast disorders
Pelvic abscess	0/58 (0%)		1/56 (1.8%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/58 (1.7%)		0/56 (0%)
Bronchopneumonia	0/58 (0%)		1/56 (1.8%)
Pneumothorax	0/58 (0%)		1/56 (1.8%)
Respiratory distress	4/58 (6.9%)		1/56 (1.8%)
Respiratory failure	1/58 (1.7%)		2/56 (3.6%)
Other (Not Including Serious) Adverse Events
	Control Arm		Granulocyte Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		32/51 (62.7%)
Blood and lymphatic system disorders
Hemolysis	0/6 (0%)	0	0/51 (0%)	0
Cardiac disorders
Sinus bradycardia	0/6 (0%)	0	0/51 (0%)	0
Sinus tachycardia	1/6 (16.7%)	3	17/51 (33.3%)	36
General disorders
Hypertension	1/6 (16.7%)	1	9/51 (17.6%)	15
Hypotension	0/6 (0%)	0	10/51 (19.6%)	14
Headache	0/6 (0%)	0	1/51 (2%)	1
Fever	1/6 (16.7%)	2	28/51 (54.9%)	81
Immune system disorders
Allergic reaction/ hypersensitivity	0/6 (0%)	0	5/51 (9.8%)	5
Musculoskeletal and connective tissue disorders
Rigors and Chills	0/6 (0%)	0	15/51 (29.4%)	42
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/6 (0%)	0	3/51 (5.9%)	3
Hypoxia	0/6 (0%)	0	8/51 (15.7%)	16
Wheezing	0/6 (0%)	0	1/51 (2%)	1
Cough	0/6 (0%)	0	0/51 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All publications and presentations resulting from studies from the TMH Network must be approved by the Publications and Presentations Committee before submission. The Sponsor (NERI) and funding agency (NHLBI) both are represented on the P&P Committee along with Network Investigators. Members of the P&P Committee can recommend changes to publications.