Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropenia
Pammi M, Brocklehurst P
Cochrane Database of Systematic Reviews. 2011;((10):):CD003956.
BACKGROUND Neonates have immature granulopoiesis, which frequently results in neutropenia after sepsis. Neutropaenic septic neonates have a higher mortality than non-neutropenic septic neonates. Therefore, granulocyte transfusion to septic neutropenic neonates may improve outcomes. OBJECTIVES The primary objective was to determine the effect of granulocyte or buffy coat transfusions as adjuncts to antibiotics, after confirmed or suspected sepsis in neutropenic neonates, on all-cause mortality during hospital stay and neurological outcome at >= year of age. Secondary objectives were to determine the effects of granulocyte transfusions on length of hospital stay in survivors to discharge, adverse effects and immunologic outcomes at >= year of age. SEARCH STRATEGY The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE and CINAHL, proceedings of the PAS conferences and ongoing trials at clinicaltrials.gov and clinical-trials.com were searched in July 2011. SELECTION CRITERIA Studies where neutropenic neonates with suspected or confirmed sepsis were randomised or quasi-randomised to granulocyte or buffy coat transfusions at any dose or duration, and reporting any outcome of interest were included. DATA COLLECTION AND ANALYSIS Relative risk (RR) and risk difference (RD) with 95% confidence intervals using the fixed effects model were reported for dichotomous outcomes. Pre-specified subgroup analyses were performed. MAIN RESULTS Four trials were eligible for inclusion. Forty-four infants with sepsis and neutropenia were randomised in three trials to granulocyte transfusions or placebo/no transfusion. In another trial, 35 infants with sepsis and neutropenia on antibiotics were randomised to granulocyte transfusion or IVIG.When granulocyte transfusion was compared with placebo or no transfusion, there was no significant difference in 'all-cause mortality' (three trials; typical RR 0.89, 95% CI 0.43 to 1.86; typical RD -0.05, 95% CI -0.31 to 0.21).When granulocyte transfusion was compared with intravenous immunoglobulin (one trial), there was a reduction in 'all-cause mortality' of borderline statistical significance (RR 0.06, 95% CI 0.00 to 1.04; RD -0.34, 95% CI -0.60 to -0.09; NNT 2.7, 95% CI 1.6 to 9.1).Pulmonary complications were the only adverse effect reported in the trials that used buffy coat transfusions. None of the trials reported on neurological outcome at one year of age or later, length of hospital stay in survivors to discharge or immunological outcome at one year of age or later. AUTHORS' CONCLUSIONS Currently, there is inconclusive evidence from randomised controlled trials (RCTs) to support or refute the routine use of granulocyte transfusions in neutropenic, septic neonates. Researchers are encouraged to conduct adequately powered multi-centre trials of granulocyte transfusions in neutropenic septic neonates.
Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis
Cairo MS, Worcester CC, Rucker RW, Hanten S, Amlie RN, Sender L, Hicks DA
Journal of Pediatrics. 1992;120((2, Pt 1):):281-5.
We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis.
Buffy coat transfusions in neutropenic neonates with presumed sepsis: a prospective, randomized trial
Baley JE, Stork EK, Warkentin PI, Shurin SB
Neonatal sepsis, accompanied by neutropenia, is associated with a high mortality. To determine whether granulocyte transfusions improve the survival of critically ill neutropenic infants, we prospectively randomized 25 infants to transfusion and nontransfusion groups, matching for birth weight (less than or equal to 1,500 g or greater than 1,500 g). Infants with necrotizing enterocolitis were randomized separately. Neutropenia was established by two successive absolute neutrophil counts less than or equal to 1,500 cells prior to randomization. The transfusion (n = 12) and nontransfusion (n = 13) groups did not differ with respect to clinical or hematologic characteristics. In 23 of 25, bone marrow aspirations were performed to determine the percentage of neutrophil storage pool. Granulocyte transfusions of buffy coats from single units of whole blood (0.1 to 0.9 X 10(9) polymorphonuclear leukocytes per kilogram) were given daily until the absolute neutrophil count increased to more than 1,500/microL. Only five infants, mostly those with necrotizing enterocolitis, required more than one transfusion. A circulating immature to total neutrophil ratio (I:T) greater than or equal to 0.80 was not predictive of an infant with a neutrophil storage pool less than or equal to 7%, and neither an I:T less than 0.80 nor a neutrophil storage pool greater than 7% were predictive of survival. Granulocyte transfusions did not improve survival when either comparing the whole group, those 17 infants with cultures positive for bacteria or viruses, the 19 infants with a circulating I:T greater than or equal to 0.80, or the nine infants with a neutrophil storage pool less than or equal to 7%.(ABSTRACT TRUNCATED AT 250 WORDS)
Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion
Wheeler JG, Chauvenet AR, Johnson CA, Block SM, Dillard R, Abramson JS
A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection. Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells). These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3). The remaining 11 (group 1) were observed. Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions. There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days. No complications of transfusion were noted. No difference in the rate of peripheral neutrophil increase was found among the three groups. The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome. Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old. The role of neutrophil transfusions in these patients remains unclear.
Improved survival of newborns receiving leukocyte transfusions for sepsis
Cairo MS, Rucker R, Bennetts GA, Hicks D, Worcester C, Amlie R, Johnson S, Katz J
To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Pretreatment demographic, clinical, and laboratory variables that were found to be insignificant in prognosis between newborns who received transfusions and newborns who did not receive transfusions included weight, gestational and postnatal age, hypoxia, acidosis, hypotension, initial absolute granulocyte count (AGC), initial levels of immunoglobulins (IgA, IgG, and IgM), and total hemolytic complement. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group (13/13, 100%) compared with the group that did not receive transfusions (6/10, 60%, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)