High Dose Granulocyte Transfusions for the Treatment of Infection in Neutropenia: The RING Study (Resolving Infection in Neutropenia With Granulocytes)

Brief Summary

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.

Primary Outcomes

Secondary Outcomes

• Graft Versus Host Disease Among Recipients of Allogeneic Stem Cell Transplantation(Measured at Day 42)
• Alloimmunization, Defined as the Appearance of Anti-human Leukocyte Antigen (HLA) or Antineutrophil Antibodies(Measured at Days 14 and 42)
• Time to Negative Blood Culture for Participants With Positive Blood Culture at Baseline(Measured through Day 42)
• Donor Availability (Proportion of Scheduled Granulocyte Transfusion Days on Which Granulocytes Were Available)(Measured through study completion)
• Discontinuation of Granulocyte Transfusions Due to Toxicity or Intolerance(Measured through Day 42)
• Overall Incidence of Adverse Effects(Measured through Day 42)
• Serious Granulocyte Transfusion Reactions, Including Febrile, Allergic, and Pulmonary Reactions (Transfusion Arm Only)(Measured within 6 hours after end of transfusion)
• Fever Resolution(Measured through Day 42)
• Time to Negative Test for Fungal Antigenemia (e.g., Galactomannan Antigenemia Among Participants With Invasive Aspergillosis)(Measured at Days 7, 14, and 42)
• Long-term Survival(Measured at Month 3)
• Serious Adverse Events in Granulocyte Donors(Measured at Week 1 after G-CSF administration)
• Evaluation of Granulocyte Yield(Measured immediately after each granulocyte donation)