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Thomas H. Price - One of the best experts on this subject based on the ideXlab platform.
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WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic Granulocyte Transfusions.
Transfusion, 2018Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Ryan W Harrison, Paul M Ness, Taye H Hamza, Susan F. AssmannAbstract:BACKGROUND Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in Granulocyte Transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily Granulocyte Transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for Granulocyte-specific antibodies using Granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the Granulocyte Transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of Transfusion reactions (either overall or pulmonary), or postTransfusion neutrophil increments. CONCLUSION The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of Granulocyte Transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing Granulocyte Transfusions.
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efficacy of Transfusion with Granulocytes from g csf dexamethasone treated donors in neutropenic patients with infection
Blood, 2015Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Michael Boeckh, Ryan W Harrison, Paul M Ness, Garrett W Nichols, Taye H HamzaAbstract:High-dose Granulocyte Transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for Granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per Transfusion of ≥0.6 × 10(9) Granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of Granulocyte Transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
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a randomized controlled trial on the efficacy of high dose Granulocyte Transfusion therapy in neutropenic patients with infection
Blood, 2014Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Ryan W Harrison, Paul M Ness, Taye H Hamza, Shelley Pulkrabek, Susan AssmanAbstract:Bacterial and fungal infections continue to be a major problem in patients with prolonged severe neutropenia. Early controlled trials suggested that Granulocyte Transfusions were modestly effective in this setting, but the doses provided were later considered inadequate. Recent studies have shown that the dose can be increased substantially by administering G-CSF ± dexamethasone to Granulocyte donors. Although these cells circulate in neutropenic recipients and appear to function normally, the evidence for clinical efficacy has been inconclusive. We report here the result of the RING study, a recently completed randomized controlled trial on the efficacy of high-dose Granulocyte Transfusion therapy, carried out as part of the NHLBI Transfusion Medicine/Hemostasis Clinical Trials Network. Fourteen clinical sites participated. Eligible subjects were those with neutropenia (ANC The target sample size was 236 subjects, designed to provide 80% power to detect a 20% difference in success rates between treatment and control groups; however, only 114 subjects could be enrolled. Patient infections were 36% invasive fungal, 27% invasive bacterial, 11% fungemia, and 26% bacteremia. Subjects in both arms were well matched in terms of demographics, underlying disease, types and sites of infection, and severity of illness. Fifty six subjects were randomized to the Granulocyte arm; 51 received at least one Transfusion; the mean time from eligibility to the first Transfusion was 2.3 +/- 1.2 days. Among these 51 subjects, the median number of Transfusions was 5 (quartiles 3 and 9), given over a median of 6 days (quartiles 4 and 11). The median number of Granulocytes administered per Transfusion was 54.9 x109 (quartiles 26.1 x109, 72.5 x109). Fourteen percent of these patients had > Grade 3 hypoxemia develop during or within six hours after a Granulocyte Transfusion, requiring ventilation in one patient (2%). No deaths were attributed to adverse effects associated with the Transfusions. Among subjects with sufficient data to determine the primary outcome, success rates were 42% (20/48) and 43% (21/49) for the Granulocyte and control groups, respectively (p> 0.99) on Intention to Treat (ITT) analysis, and 49% (17/35) and 41% (16/39), respectively, for subjects who adhered to their assigned treatments (Per Protocol (PP) analysis)(p=0.64). There was also no significant difference between treatment groups in a model of the primary outcome that adjusted for baseline prognostic factors (e.g. ventilator use, high Zubrod score). Differences in primary end point success rates for Granulocyte and control arms did not differ significantly for any infection type whether analyzed by ITT or PP. Outcomes for patients who received the first Transfusion within 2 days of eligibility were similar to outcomes for patients who received the first Transfusion later. For patients who received at least three Granulocyte Transfusions, those who received an average dose per Transfusion of >50x109 Granulocytes had a higher success rate (57.7%)(n=26) than those receiving Because of incomplete patient enrollment, the power of this study to detect a 20% difference in overall success rates was reduced to approximately 40%. Thus it is possible that a true convincing favorable effect was missed, particularly, as suggested, in the subset of patients who received daily Transfusions containing at least 50x109 Granulocytes per Transfusion. Disclosures Off Label Use: In the study being discussed, G-CSF is administered to normal blood donors. This is an off-label use of G-CSF. McCullough:Fresenius/Kabe: Membership on an entity9s Board of Directors or advisory committees. Ness:Terumo BCT: Consultancy.
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Granulocyte Transfusion therapy a new era
Current Opinion in Hematology, 2009Co-Authors: David C. Dale, Thomas H. PriceAbstract:Granulocyte Transfusion therapy is not a new idea; since the 1930’s hematologists have tried to find ways to collect and transfuse enough Granulocytes to prevent and treat infections in severely neutropenic patients. It has been a long road with periods of excitement and disappointment. Without question, the availability of the myeloid growth factors, particularly Granulocyte colony-stimulating factor (G-CSF), and new antibiotics and antifungal agents have improved supportive care. Nevertheless, severe neutropenia remains an important and serious complication of cancer chemotherapy and hematopoietic stem cell transplantation, and the mortality rate is still about ten percent for patients admitted to U S hospital with febrile neutropenia. (1) With prolonged neutropenia, fungal infections are still the most difficult clinical problem. The strongest predictor of recovery from invasive fungal infections in this setting is recovery of neutrophil production by the marrow and an adequate number of blood and tissue neutrophils. (2) Neutrophil Transfusion therapy represents a possible way to bridge the gap between marrow suppression and neutrophil recovery. In the early 1990’s it was established that G-CSF is a powerful mobilizer of Granulocytes from the marrow to the blood in normal donors for Transfusion to severely neutropenic patients. (3) A study by Bensinger, et. al. then established that large numbers of neutrophils can be harvested by centrifuge leukapheresis from normal donors treated with a single dose of G-CSF. (4) When these cells were transfused to neutropenic recipients, they circulated normally and the effect of the Transfusion lasted for at least 24 hours. Subsequent studies established that addition of dexamethasone to G-CSF enhanced the harvest almost two-fold, permitting the collection of approximately 8 × 1010 neutrophils, sufficient cells to raise the circulating count of a severely neutropenic patients to a normal level. (5) Further trials then showed that these cells also could migrate to a site of inflammation and had normal functional characteristics. (6) This was the start of a new era for neutrophil Transfusion therapy. Since these original trials, several studies have suggested that Granulocyte Transfusion from G-CSF/dexamethasone stimulated donors are effective for the treatment of infections in severely neutropenic patients, but there is not yet any definitive proof of clinical benefit. (7) Now for the first time, a phase III randomized controlled clinical trial is underway to evaluate the effectiveness of transfusing large numbers of G-CSF/dexamethasone mobilized Granulocytes under sponsorship of the National Heart, Lung and Blood Institute, NIH, conducted by the Transfusion Medicine/Hemostasis Clinical Trials Network. The study will evaluate neutropenic patients who have undergone dose-intensive chemotherapy or hematopoietic stem cell transplantation within the last 60 days who have proven or probable infections. The objective is to evaluate the benefit of treating patients with G-CSF/dexamethasone mobilized Granulocyte Transfusion as an adjunct to organism-directed antimicrobial therapy. The control group will receive standard care with organism-directed antimicrobial therapy alone. Subjects in the Granulocyte arm will receive daily Transfusions for up to 42 days and all enrolled subjects will be followed for up to three months to evaluate survival benefits. The primary end point is a composite one: survival and a microbial response, both evaluated at 42 days after randomization. One of the most important aspects of this study is the use of community donors. This part of the study plan is based upon observations in preliminary trials that allo-immunization occur slowly if at all in this patient population, permitting many days of Transfusion of cells from a general donor population. Many other aspects of the trial, for example, the cytomegalovirus status of the donor and the recipient, collection techniques, storage duration of the Granulocytes, need for irradiation of the cells to be transfused, timing of Granulocyte Transfusions in relationship to antimicrobial therapy and other factors have been worked out through careful studies over the last several years. This trial will also reinvestigate many of these factors and provide valuable information on contemporary patterns of infection in severely neutropenic patients, particularly on the diagnosis, treatment and outcomes for high risk fungal infections in this setting. The study, called the RING (Resolving Infections in Neutropenia with Granulocytes) study, opened mid-year 2008 and aims to enroll 236 subjects (118 in each arm), based upon estimates of the effectiveness of current treatment and risk of mortality in this population. The Transfusion Medicine/Hemostasis Clinical Trials Network is interested in adding out-of-network participating centers and investigators. Interested parties should contact Dr. Thomas Price (gro.cbsp@ecirpht) or Julie Miller (moc.ecneicsiren@relliMJ) at the New England Research Institue (the study’s data coordinating center).
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Granulocyte Transfusion current status
Seminars in Hematology, 2007Co-Authors: Thomas H. PriceAbstract:Infection associated with therapy-related neutropenia continues to be a major cause of morbidity and mortality. Renewed interest in Granulocyte Transfusion therapy as treatment for this condition has been generated by the observation that large doses of Granulocytes can be obtained from donors who have been stimulated with Granulocyte colony-stimulating factor (G-CSF). Granulocytes collected from these donors have been shown to effectively raise the patient's neutrophil count and appear to function normally as judged both by in vitro and in vivo measures. The evidence for clinical efficacy is limited to that of case reports and small series, and the results are not uniform. Randomized controlled clinical trials are needed to determine whether this therapy is useful in either clearing infections or prolonging survival.
Kai Hübel - One of the best experts on this subject based on the ideXlab platform.
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Granulocyte Transfusion therapy for treatment of infections after cytotoxic chemotherapy.
Onkologie, 2003Co-Authors: Kai Hübel, A. EngertAbstract:Opportunistic fungal infections and antibiotic-refractory bacterial infections remain important causes of morbidity and mortality in neutropenic individuals. Furthermore, the expanding use of dose-intensive cancer treatment strategies has increased the frequency of prolonged neutropenia. Therefore, the Transfusion of Granulocytes should be a logical therapeutic approach. Substantial progress has been made in the field of Granulocyte Transfusion therapy during the past decade. Interest in Granulocyte Transfusion therapy has been rekindled by both the use of hematopoietic growth factors to mobilize neutrophils and modern leukapheresis techniques. Moreover, promising results were observed in the use of community donors and in Granulocyte storage experiments, which could enhance the ability of blood banks for institution of Granulocyte concentrates. Recent clinical trials suggest that Granulocyte Transfusion therapy may be effective and well-tolerated in the neutropenic patient affected by life-threatening infections. These results must be confirmed in controlled, clinical trials.
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Granulocyte Transfusion therapy for infections in candidates and recipients of hpc transplantation a comparative analysis of feasibility and outcome for community donors versus related donors
Transfusion, 2002Co-Authors: Kai Hübel, Thomas H. Price, David C. Dale, Rachel A Carter, Conrad W Liles, Raleigh A Bowden, S D Rowley, Thomas R Chauncey, William I Bensinger, Michael BoeckhAbstract:BACKGROUND: Feasibility, response to Granulocyte Transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank-based unrelated donors program, a prospective Granulocyte study using family donors, and matched control patients without Granulocyte Transfusion therapy. STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received Granulocyte concentrates from unrelated donors, 34 patients (219 collections) received Granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per μL and documented invasive fungal or bacterial infections. RESULTS: There was a median delay of 3 days (range, 0-14) in patients receiving Transfusions from unrelated donors between day of diagnosis of infection and start of Granulocyte Transfusion therapy as compared with a median delay of 5 days (range, 0-25) in patients receiving Transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh Transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan-Meier analysis revealed no difference between all cohorts in overall 6-month survival (p = 0.28, log-rank) or event-free survival (p = 0.17, log-rank). CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of Granulocyte Transfusion therapy.
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current status of Granulocyte neutrophil Transfusion therapy for infectious diseases
The Journal of Infectious Diseases, 2001Co-Authors: Kai Hübel, David C. Dale, Andreas Engert, Conrad W LilesAbstract:The Transfusion of neutrophils, or Granulocyte Transfusion therapy, has long been considered as a logical approach to the treatment of severe bacterial and fungal infections in patients with prolonged neutropenia or intrinsic defects in neutrophil function. However, despite numerous clinical trials, the efficacy and safety of Granulocyte Transfusion therapy remain controversial. Efficacy has been compromised largely by the inability to transfuse sufficient quantities of functionally active neutrophils to patients. The recent use of recombinant Granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in donors before centrifugation leukapheresis has rekindled interest in the potential clinical applications of Granulocyte Transfusion therapy. This review focuses on the use of G-CSF for donor stimulation and summarizes the current status of Granulocyte Transfusion therapy for treatment of infectious diseases.
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Granulocyte Transfusion therapy: update on potential clinical applications.
Current opinion in hematology, 2001Co-Authors: Kai Hübel, David C. Dale, W. Conrad LilesAbstract:The clinical usefulness of Granulocyte Transfusions for treatment or prevention of life-threatening bacterial and fungal infections remains controversial. Clinical benefit has long been limited by insufficient donor stimulation regimens and suboptimal leukapheresis techniques. Methodologic progress, in particular mobilization of neutrophils in healthy donors by administration of G-CSF, has significantly enhanced leukapheresis yields. A newly published study indicates that unrelated community donors can be effectively and safely used as an alternative to related family donors. Furthermore, several recent studies suggest that it may be possible to store Granulocyte concentrates for 24 to 48 hours with adequate preservation of neutrophil function. This review summarizes the current role of Granulocyte Transfusion therapy in infectious diseases and highlights important recent advances.
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Use of G-CSF for Granulocyte Transfusion therapy.
Cytokines cellular & molecular therapy, 2000Co-Authors: Kai Hübel, David C. Dale, Andreas Engert, W. Conrad LilesAbstract:Patients with neutropenia, especially neutropenia following aggressive myeloablative therapy, are at high risk for developing infectious complications caused by bacteria and opportunistic fungi. Infections remain one of the leading causes of treatment failure in patients with cancer. Thus, new and innovative therapeutic strategies are needed for management of neutropenic patients with infection. Because neutrophils represent the first line of host defense, Granulocyte Transfusion therapy should be a logical therapeutic approach. Although such therapy has been employed sporadically for several decades, clinical benefit has been compromised by technical problems and low Granulocyte yields resulting from inadequate donor stimulation. The discovery of Granulocyte colony-stimulatng factor (G-CSF) as a means to elevate blood neutrophil counts when administered to normal donors has rekindled interest in Granulocyte Transfusion therapy. Extensive experience has been gained worldwide with G-CSF in clinical practic...
David C. Dale - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Current Status of Granulocyte (Neutrophil) Transfusion Therapy for Infectious Diseases
2016Co-Authors: Kai Huèbel, David C. Dale, Andreas Engert, Conrad W LilesAbstract:The Transfusion of neutrophils, or Granulocyte Transfusion therapy, has long been considered as a logical approach to the treatment of severe bacterial and fungal infections in patients with prolonged neutropenia or intrinsic defects in neutrophil function. However, despite nu-merous clinical trials, the ef®cacy and safety of Granulocyte Transfusion therapy remain con-troversial. Ef®cacy has been compromised largely by the inability to transfuse suf®cient quan-tities of functionally active neutrophils to patients. The recent use of recombinant Granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in donors before centrifugation leukapheresis has rekindled interest in the potential clinical applications of Granulocyte trans-fusion therapy. This review focuses on the use of G-CSF for donor stimulation and summarizes the current status of Granulocyte Transfusion therapy for treatment of infectious diseases. Neutrophils (polymorphonuclear leukocytes [PMNL]) play an integral role in host defense against potential bacterial and op-portunistic fungal pathogens. The expanding use of dose-inten-sive cancer treatment strategies, such as high-dose chemotherapy and bone marrow and hematopoietic stem cell transplantation
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Granulocyte Transfusion therapy a new era
Current Opinion in Hematology, 2009Co-Authors: David C. Dale, Thomas H. PriceAbstract:Granulocyte Transfusion therapy is not a new idea; since the 1930’s hematologists have tried to find ways to collect and transfuse enough Granulocytes to prevent and treat infections in severely neutropenic patients. It has been a long road with periods of excitement and disappointment. Without question, the availability of the myeloid growth factors, particularly Granulocyte colony-stimulating factor (G-CSF), and new antibiotics and antifungal agents have improved supportive care. Nevertheless, severe neutropenia remains an important and serious complication of cancer chemotherapy and hematopoietic stem cell transplantation, and the mortality rate is still about ten percent for patients admitted to U S hospital with febrile neutropenia. (1) With prolonged neutropenia, fungal infections are still the most difficult clinical problem. The strongest predictor of recovery from invasive fungal infections in this setting is recovery of neutrophil production by the marrow and an adequate number of blood and tissue neutrophils. (2) Neutrophil Transfusion therapy represents a possible way to bridge the gap between marrow suppression and neutrophil recovery. In the early 1990’s it was established that G-CSF is a powerful mobilizer of Granulocytes from the marrow to the blood in normal donors for Transfusion to severely neutropenic patients. (3) A study by Bensinger, et. al. then established that large numbers of neutrophils can be harvested by centrifuge leukapheresis from normal donors treated with a single dose of G-CSF. (4) When these cells were transfused to neutropenic recipients, they circulated normally and the effect of the Transfusion lasted for at least 24 hours. Subsequent studies established that addition of dexamethasone to G-CSF enhanced the harvest almost two-fold, permitting the collection of approximately 8 × 1010 neutrophils, sufficient cells to raise the circulating count of a severely neutropenic patients to a normal level. (5) Further trials then showed that these cells also could migrate to a site of inflammation and had normal functional characteristics. (6) This was the start of a new era for neutrophil Transfusion therapy. Since these original trials, several studies have suggested that Granulocyte Transfusion from G-CSF/dexamethasone stimulated donors are effective for the treatment of infections in severely neutropenic patients, but there is not yet any definitive proof of clinical benefit. (7) Now for the first time, a phase III randomized controlled clinical trial is underway to evaluate the effectiveness of transfusing large numbers of G-CSF/dexamethasone mobilized Granulocytes under sponsorship of the National Heart, Lung and Blood Institute, NIH, conducted by the Transfusion Medicine/Hemostasis Clinical Trials Network. The study will evaluate neutropenic patients who have undergone dose-intensive chemotherapy or hematopoietic stem cell transplantation within the last 60 days who have proven or probable infections. The objective is to evaluate the benefit of treating patients with G-CSF/dexamethasone mobilized Granulocyte Transfusion as an adjunct to organism-directed antimicrobial therapy. The control group will receive standard care with organism-directed antimicrobial therapy alone. Subjects in the Granulocyte arm will receive daily Transfusions for up to 42 days and all enrolled subjects will be followed for up to three months to evaluate survival benefits. The primary end point is a composite one: survival and a microbial response, both evaluated at 42 days after randomization. One of the most important aspects of this study is the use of community donors. This part of the study plan is based upon observations in preliminary trials that allo-immunization occur slowly if at all in this patient population, permitting many days of Transfusion of cells from a general donor population. Many other aspects of the trial, for example, the cytomegalovirus status of the donor and the recipient, collection techniques, storage duration of the Granulocytes, need for irradiation of the cells to be transfused, timing of Granulocyte Transfusions in relationship to antimicrobial therapy and other factors have been worked out through careful studies over the last several years. This trial will also reinvestigate many of these factors and provide valuable information on contemporary patterns of infection in severely neutropenic patients, particularly on the diagnosis, treatment and outcomes for high risk fungal infections in this setting. The study, called the RING (Resolving Infections in Neutropenia with Granulocytes) study, opened mid-year 2008 and aims to enroll 236 subjects (118 in each arm), based upon estimates of the effectiveness of current treatment and risk of mortality in this population. The Transfusion Medicine/Hemostasis Clinical Trials Network is interested in adding out-of-network participating centers and investigators. Interested parties should contact Dr. Thomas Price (gro.cbsp@ecirpht) or Julie Miller (moc.ecneicsiren@relliMJ) at the New England Research Institue (the study’s data coordinating center).
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Granulocyte Transfusion therapy for infections in candidates and recipients of hpc transplantation a comparative analysis of feasibility and outcome for community donors versus related donors
Transfusion, 2002Co-Authors: Kai Hübel, Thomas H. Price, David C. Dale, Rachel A Carter, Conrad W Liles, Raleigh A Bowden, S D Rowley, Thomas R Chauncey, William I Bensinger, Michael BoeckhAbstract:BACKGROUND: Feasibility, response to Granulocyte Transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank-based unrelated donors program, a prospective Granulocyte study using family donors, and matched control patients without Granulocyte Transfusion therapy. STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received Granulocyte concentrates from unrelated donors, 34 patients (219 collections) received Granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per μL and documented invasive fungal or bacterial infections. RESULTS: There was a median delay of 3 days (range, 0-14) in patients receiving Transfusions from unrelated donors between day of diagnosis of infection and start of Granulocyte Transfusion therapy as compared with a median delay of 5 days (range, 0-25) in patients receiving Transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh Transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan-Meier analysis revealed no difference between all cohorts in overall 6-month survival (p = 0.28, log-rank) or event-free survival (p = 0.17, log-rank). CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of Granulocyte Transfusion therapy.
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current status of Granulocyte neutrophil Transfusion therapy for infectious diseases
The Journal of Infectious Diseases, 2001Co-Authors: Kai Hübel, David C. Dale, Andreas Engert, Conrad W LilesAbstract:The Transfusion of neutrophils, or Granulocyte Transfusion therapy, has long been considered as a logical approach to the treatment of severe bacterial and fungal infections in patients with prolonged neutropenia or intrinsic defects in neutrophil function. However, despite numerous clinical trials, the efficacy and safety of Granulocyte Transfusion therapy remain controversial. Efficacy has been compromised largely by the inability to transfuse sufficient quantities of functionally active neutrophils to patients. The recent use of recombinant Granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in donors before centrifugation leukapheresis has rekindled interest in the potential clinical applications of Granulocyte Transfusion therapy. This review focuses on the use of G-CSF for donor stimulation and summarizes the current status of Granulocyte Transfusion therapy for treatment of infectious diseases.
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Granulocyte Transfusion therapy: update on potential clinical applications.
Current opinion in hematology, 2001Co-Authors: Kai Hübel, David C. Dale, W. Conrad LilesAbstract:The clinical usefulness of Granulocyte Transfusions for treatment or prevention of life-threatening bacterial and fungal infections remains controversial. Clinical benefit has long been limited by insufficient donor stimulation regimens and suboptimal leukapheresis techniques. Methodologic progress, in particular mobilization of neutrophils in healthy donors by administration of G-CSF, has significantly enhanced leukapheresis yields. A newly published study indicates that unrelated community donors can be effectively and safely used as an alternative to related family donors. Furthermore, several recent studies suggest that it may be possible to store Granulocyte concentrates for 24 to 48 hours with adequate preservation of neutrophil function. This review summarizes the current role of Granulocyte Transfusion therapy in infectious diseases and highlights important recent advances.
Conrad W Liles - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Current Status of Granulocyte (Neutrophil) Transfusion Therapy for Infectious Diseases
2016Co-Authors: Kai Huèbel, David C. Dale, Andreas Engert, Conrad W LilesAbstract:The Transfusion of neutrophils, or Granulocyte Transfusion therapy, has long been considered as a logical approach to the treatment of severe bacterial and fungal infections in patients with prolonged neutropenia or intrinsic defects in neutrophil function. However, despite nu-merous clinical trials, the ef®cacy and safety of Granulocyte Transfusion therapy remain con-troversial. Ef®cacy has been compromised largely by the inability to transfuse suf®cient quan-tities of functionally active neutrophils to patients. The recent use of recombinant Granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in donors before centrifugation leukapheresis has rekindled interest in the potential clinical applications of Granulocyte trans-fusion therapy. This review focuses on the use of G-CSF for donor stimulation and summarizes the current status of Granulocyte Transfusion therapy for treatment of infectious diseases. Neutrophils (polymorphonuclear leukocytes [PMNL]) play an integral role in host defense against potential bacterial and op-portunistic fungal pathogens. The expanding use of dose-inten-sive cancer treatment strategies, such as high-dose chemotherapy and bone marrow and hematopoietic stem cell transplantation
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Granulocyte Transfusion therapy for infections in candidates and recipients of hpc transplantation a comparative analysis of feasibility and outcome for community donors versus related donors
Transfusion, 2002Co-Authors: Kai Hübel, Thomas H. Price, David C. Dale, Rachel A Carter, Conrad W Liles, Raleigh A Bowden, S D Rowley, Thomas R Chauncey, William I Bensinger, Michael BoeckhAbstract:BACKGROUND: Feasibility, response to Granulocyte Transfusion therapy, and clinical outcome were compared among HPC transplant recipients enrolled in a prospective study of a community blood bank-based unrelated donors program, a prospective Granulocyte study using family donors, and matched control patients without Granulocyte Transfusion therapy. STUDY DESIGN AND METHODS: Overall, 40 patients (327 collections) received Granulocyte concentrates from unrelated donors, 34 patients (219 collections) received Granulocyte concentrates from related donors, and 74 patients served as controls. Study entry criteria for patients included an absolute neutrophil count (ANC) of less than 200 per μL and documented invasive fungal or bacterial infections. RESULTS: There was a median delay of 3 days (range, 0-14) in patients receiving Transfusions from unrelated donors between day of diagnosis of infection and start of Granulocyte Transfusion therapy as compared with a median delay of 5 days (range, 0-25) in patients receiving Transfusions from related donors (p = 0.01). The ANC increment after the first, second, and seventh Transfusions in patients who had community donors was significantly higher or comparable to patients who had family donors. Overall, clinical outcome was comparable between the three patient groups. Kaplan-Meier analysis revealed no difference between all cohorts in overall 6-month survival (p = 0.28, log-rank) or event-free survival (p = 0.17, log-rank). CONCLUSION: These results suggest that future efficacy trials should consider inclusion of unrelated community donors for timely institution of Granulocyte Transfusion therapy.
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current status of Granulocyte neutrophil Transfusion therapy for infectious diseases
The Journal of Infectious Diseases, 2001Co-Authors: Kai Hübel, David C. Dale, Andreas Engert, Conrad W LilesAbstract:The Transfusion of neutrophils, or Granulocyte Transfusion therapy, has long been considered as a logical approach to the treatment of severe bacterial and fungal infections in patients with prolonged neutropenia or intrinsic defects in neutrophil function. However, despite numerous clinical trials, the efficacy and safety of Granulocyte Transfusion therapy remain controversial. Efficacy has been compromised largely by the inability to transfuse sufficient quantities of functionally active neutrophils to patients. The recent use of recombinant Granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in donors before centrifugation leukapheresis has rekindled interest in the potential clinical applications of Granulocyte Transfusion therapy. This review focuses on the use of G-CSF for donor stimulation and summarizes the current status of Granulocyte Transfusion therapy for treatment of infectious diseases.
Ronald G. Strauss - One of the best experts on this subject based on the ideXlab platform.
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WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic Granulocyte Transfusions.
Transfusion, 2018Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Ryan W Harrison, Paul M Ness, Taye H Hamza, Susan F. AssmannAbstract:BACKGROUND Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in Granulocyte Transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily Granulocyte Transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for Granulocyte-specific antibodies using Granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the Granulocyte Transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of Transfusion reactions (either overall or pulmonary), or postTransfusion neutrophil increments. CONCLUSION The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of Granulocyte Transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing Granulocyte Transfusions.
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efficacy of Transfusion with Granulocytes from g csf dexamethasone treated donors in neutropenic patients with infection
Blood, 2015Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Michael Boeckh, Ryan W Harrison, Paul M Ness, Garrett W Nichols, Taye H HamzaAbstract:High-dose Granulocyte Transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for Granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per Transfusion of ≥0.6 × 10(9) Granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of Granulocyte Transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
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a randomized controlled trial on the efficacy of high dose Granulocyte Transfusion therapy in neutropenic patients with infection
Blood, 2014Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Ryan W Harrison, Paul M Ness, Taye H Hamza, Shelley Pulkrabek, Susan AssmanAbstract:Bacterial and fungal infections continue to be a major problem in patients with prolonged severe neutropenia. Early controlled trials suggested that Granulocyte Transfusions were modestly effective in this setting, but the doses provided were later considered inadequate. Recent studies have shown that the dose can be increased substantially by administering G-CSF ± dexamethasone to Granulocyte donors. Although these cells circulate in neutropenic recipients and appear to function normally, the evidence for clinical efficacy has been inconclusive. We report here the result of the RING study, a recently completed randomized controlled trial on the efficacy of high-dose Granulocyte Transfusion therapy, carried out as part of the NHLBI Transfusion Medicine/Hemostasis Clinical Trials Network. Fourteen clinical sites participated. Eligible subjects were those with neutropenia (ANC The target sample size was 236 subjects, designed to provide 80% power to detect a 20% difference in success rates between treatment and control groups; however, only 114 subjects could be enrolled. Patient infections were 36% invasive fungal, 27% invasive bacterial, 11% fungemia, and 26% bacteremia. Subjects in both arms were well matched in terms of demographics, underlying disease, types and sites of infection, and severity of illness. Fifty six subjects were randomized to the Granulocyte arm; 51 received at least one Transfusion; the mean time from eligibility to the first Transfusion was 2.3 +/- 1.2 days. Among these 51 subjects, the median number of Transfusions was 5 (quartiles 3 and 9), given over a median of 6 days (quartiles 4 and 11). The median number of Granulocytes administered per Transfusion was 54.9 x109 (quartiles 26.1 x109, 72.5 x109). Fourteen percent of these patients had > Grade 3 hypoxemia develop during or within six hours after a Granulocyte Transfusion, requiring ventilation in one patient (2%). No deaths were attributed to adverse effects associated with the Transfusions. Among subjects with sufficient data to determine the primary outcome, success rates were 42% (20/48) and 43% (21/49) for the Granulocyte and control groups, respectively (p> 0.99) on Intention to Treat (ITT) analysis, and 49% (17/35) and 41% (16/39), respectively, for subjects who adhered to their assigned treatments (Per Protocol (PP) analysis)(p=0.64). There was also no significant difference between treatment groups in a model of the primary outcome that adjusted for baseline prognostic factors (e.g. ventilator use, high Zubrod score). Differences in primary end point success rates for Granulocyte and control arms did not differ significantly for any infection type whether analyzed by ITT or PP. Outcomes for patients who received the first Transfusion within 2 days of eligibility were similar to outcomes for patients who received the first Transfusion later. For patients who received at least three Granulocyte Transfusions, those who received an average dose per Transfusion of >50x109 Granulocytes had a higher success rate (57.7%)(n=26) than those receiving Because of incomplete patient enrollment, the power of this study to detect a 20% difference in overall success rates was reduced to approximately 40%. Thus it is possible that a true convincing favorable effect was missed, particularly, as suggested, in the subset of patients who received daily Transfusions containing at least 50x109 Granulocytes per Transfusion. Disclosures Off Label Use: In the study being discussed, G-CSF is administered to normal blood donors. This is an off-label use of G-CSF. McCullough:Fresenius/Kabe: Membership on an entity9s Board of Directors or advisory committees. Ness:Terumo BCT: Consultancy.
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Rebirth of Granulocyte Transfusions: should it involve pediatric oncology and transplant patients?
Journal of pediatric hematology oncology, 1999Co-Authors: Ronald G. StraussAbstract:Abstract Several methodologic advances, particularly use of recombinant Granulocyte colony stimulating factor to stimulate donors, have made it possible to collect extraordinarily large numbers of normal neutrophils for Transfusion into neutropenic patients with life-threatening infections. Because larger doses of neutrophils can be transfused, renewed interest has arisen in the use of neutrophil (Granulocyte) Transfusions to treat adult oncology patients and progenitor cell transplant recipients, in whom neutropenia complicated by severe infections persists as a significant problem, despite combination antibiotic therapy, recombinant cytokines, myeloid growth factors, and use of mobilized peripheral blood progenitor cells. In this commentary, consideration is given as to whether pediatric oncology and transplant patients might benefit from modern Granulocyte Transfusion therapy. If children are found to experience significant morbidity or mortality from neutropenic infections despite modern supportive care, it is logical to explore the efficacy, potential toxicity, and cost-effectiveness of Granulocyte Transfusion therapy by properly designed, randomized clinical trials.
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Granulocyte Transfusion therapy.
Hematology oncology clinics of North America, 1994Co-Authors: Ronald G. StraussAbstract:Although the efficacy of therapeutic Granulocyte Transfusions as treatment for progressive infections in severely neutropenic patients is supported by the medical literature, this form of therapy is not widely accepted because it has been extremely difficult to transfuse an adequate dose of compatible Granulocytes. Recently, the possibility has been raised to greatly increase the number of Granulocytes collected by stimulating normal donors with recombinant Granulocyte colony-stimulating factor. Accordingly, it is reasonable to reassess the possible role for Granulocyte Transfusions as therapy for progressive bacterial, yeast, and fungal infections.
