Therapeutic transfusions of granulocytes collected by simple bag method for children with cancer and neutropenic infections: results of a single-centre pilot study

BACKGROUND AND OBJECTIVES: Granulocyte transfusion therapy (GTX) can be effective for life-threatening infections unresponsive to conventional antimicrobial therapies in severely neutropenic children with cancer. We developed a new granulocyte collection method, named the 'bag method', in which apheresis, hydroxyethyl starch (HES) or dexamethasone are not used. We undertook a pilot study to determine the feasibility and the safety of GTX collected by the bag method for children with cancer and life-threatening infections. MATERIALS AND METHODS: A total of 25 GTX were administered to 13 patients (median age 3 years, range: 0.3-17; median weight 10.6 kg, range: 4.5-49.8) with neutropenia-related infections. Thirteen blood-relative donors received granulocyte colony-stimulating factor (G-CSF) (5-10 microg/kg), subcutaneously, 14 h before collection. Major end-points were granulocyte yields, post-transfusion absolute neutrophil counts (ANC) in patients, donor and patient safety, and clinical outcome on day 30. RESULTS: The median yield of ANC per 400 ml of processed whole blood was 6.2 x 10(9) (range: 2.5-15.0 x 10(9)). Patients received a mean of 6.4 +/- 0.8 x 10(8) granulocytes per kg of body weight per transfusion. The 1-h and 24-h post-transfusion ANC rose to 607 +/- 124/microl and 704 +/- 300/microl, respectively, from the baseline of 21/microl before the first GTX. Adverse reactions were observed in five of 13 donors (bone pain, headache, vasovagal reaction; all < or = grade 2) and in two of 25 transfusions of 13 patients (transient hypoxia; grade 3). Ten patients had favourable responses, and infection resolved in nine patients. CONCLUSIONS: The bag method without apheresis relieves the physical load of donors and enables patients with a low body weight to provide an adequate dose of granulocytes.     

Granulocyte transfusion

PURPOSE OF REVIEW: Granulocyte transfusions have been used for more than four decades. Several issues have complicated the analysis of previous studies, including the utilization of improved antimicrobials, the effects of recipient alloimmunization and variable cell dose. The use of granulocyte colony-stimulating factor for donor stimulation has revived interest in granulocyte transfusion. The aim of this review is to evaluate the most recent studies in granulocyte transfusion therapy and their clinical applicability. RECENT FINDINGS: Granulocyte colony-stimulating factor use has increased the granulocyte yield by approximately fourfold. Multiple recent studies have shown that granulocyte transfusions can be helpful in controlling severe infections progressing despite the use of appropriate antibiotics, with a response rate of 40-80% with variability in results depending on patient characteristics. This benefit is limited to a small patient population as the incidence of prolonged reversible neutropenia is relatively small. Severe side effects have been rare in those studies. SUMMARY: Granulocyte transfusions are beneficial in neutropenic patients with severe uncontrolled infection. The underlying disease process is the major determinant of outcome in these patients. Because granulocyte transfusions are not commonly used, centers are not currently able to provide transfusions in a timely fashion. Nonalloimmunized patients can receive cells from nonmatched ABO compatible donors, while alloimmunized patients should receive granulocytes from either HLA-matched donors or donors selected by leukoagglutination or lymphocytotoxicity crossmatching. Further studies are needed to clarify the optimal starting time and frequency of transfusions, and the best method for identifying donor-recipient compatibility.     

Granulocyte transfusion as a treatment for enterococcal meningoencephalitis after allogeneic bone marrow transplantation from an unrelated donor

Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated. A 37-year-old man developed enterococcal meningoencephalitis during a severely granulocytopenic pre-engraftment period after BMT. Despite therapy with appropriate antibiotics, cultures of blood and cerebro-spinal fluid (CSF) continued to grow Enterococcus faecalis, and he developed rapid mental deterioration and seizure. Granulocytes were collected from his HLA-mismatched, ABO-matched sibling with subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) and oral dexamethazone. Transfusion of 4.4 x 10(10) granulocytes resulted in a 12-h post-transfusion granulocyte increment of 2.0 x 10(9)/l, and maintained peripheral blood granulocyte counts above 0.5 x 10(9)/l for 3 days. A rapid increase of granulocytes in CSF was also observed, and cultures of blood and CSF became negative after GTX. A transient worsening of seizure was observed as a potential side effect of GTX. The patient subsequently developed septic shock because of Pseudomonas aeruginosa and died. Further studies are warranted to evaluate the clinical efficacy of GTX for the treatment of uncontrolled infections in granulocytopenic stem cell transplant recipients.     

Efficacy and safety of G-CSF mobilized granulocyte transfusions in four neutropenic children with sepsis and invasive fungal infection

Background: Bacterial and fungal infections are serious complications of cancer therapy. Especially during longstanding neutropenia, patients are at risk for life-threatening infections. The aim of this study was to assess the effect and safety of G-CSF mobilized granulocyte transfusions (GTX) in four neutropenic pediatric patients with sepsis. Patients and Methods: The patients were between 4.6–17.5 years old and their diagnoses included very severe aplastic anemia, non-Hodgkin's lymphoma (NHL) and acute myeloid leukemia. Before GTX, all patients had fever despite antibiotic and antimycotic therapy, neutropenia (absolute neutrophil count ANC < 500/μl), increasing C-reactive protein (CRP) values, hypotension requiring dopamine infusion and three patients needed supplemental oxygen. The granulocyte donors received G-CSF (Neupogen™, 5 μg/kg body weight) 12 h prior to granulocyte apheresis. Results: In total, 40 GTX were performed (range 2–28 per patient). The mean increase of the granulocyte count 1 h after GTX was 1,310/μl (range 200–2,950/μl). Within the period of GTX the CRP values decreased in all patients. During or 24 h after the last GTX, the hypotension resolved and supplemental oxygen was stopped. One GTX was discontinued because of oxygen desaturation. Conclusion: GTX were a safe therapeutic measure with beneficial effects on serious infections in neutropenic children. Received: September 25, 2001 · Revision accepted: March 13, 2002 L. Grigull (corresponding author)     

Use of fresh‐frozen plasma at Royal Darwin Hospital: a retrospective audit

Background: The aim of the study was to assess the appropriateness of use of fresh‐frozen plasma (FFP) at Royal Darwin Hospital against the National Health and Medical Research Council and Australian and New Zealand Society for Blood Transfusion guidelines. Methods: A retrospective review of blood product request forms, online pathology storage system data, pathology records and clinical notes between 1 January 2006 and 31 December 2006 was carried out. The appropriateness of requests was assessed against existing guidelines. The percentage of appropriate and inappropriate FFP transfusions was obtained. Results: Six hundred and forty‐eight of 950 units (68%) of FFP were used with an appropriate indication as per National Health and Medical Research Council/Australian and New Zealand Society for Blood Transfusion guidelines. Of the remaining units, 14% (137 units) was given without a clear indication and a decision of appropriateness could not be established for 17% (165 units) because of inadequate clinical or pathology information (e.g. coagulation results). Multiple issues around prescribing practice were identified. Conclusion: There is significant use of FFP at Royal Darwin Hospital without clear clinical indication. The employment of a transfusion nurse to monitor use of FFP (and other blood products) and provide education is aimed at improving transfusion efficiency and patient safety.     

Granulocyte transfusion in the G-CSF era

Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of granulocytes delivered. Collection of granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20 to approximately 30 x 10(9) neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8 x 10(10) cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.     

Clinical outcome of granulocyte transfusion therapy for the treatment of refractory infection in neutropenic patients with hematological diseases

Neutropenic patients with hematological diseases are prone to severe infections. Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic approach for these problems. However, the efficacy and complications of GTX have not been well identified. We retrospectively analyzed the clinical outcomes of GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions for 47 patients, 72.3% of these patients’ infections were effectively improved, and the overall survival rates at 30 and 120 days were 66.0 and 57.5%, respectively. The patients who experienced neutrophil recovery within 10 days after their therapy initiation had a better response and long-term survival period (14/15, 93.3%, vs 20/32, 62.5%, P?=?0.037). Higher-dose granulocytes (>?2.55?×?10⁸/kg) might improve the effective rate of infection in the patients who had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P?=?0.049). In addition, GTX benefited the patients who suffered from pulmonary bacterial infections (16/20, 80%) compared with the bloodstream infection group (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data showed that GTX did not affect the incidence of graft-versus-host disease (GVHD) and cytomegalovirus viremia when patients received further HSCT treatment. Collectively, GTX was an adjunct treatment modality for severely neutropenic patients who were likely to experience hematopoietic recovery. More randomized trials are needed to verify the efficacy and complications of GTX therapy.     

Granulocyte transfusions in children with chronic granulomatous disease and invasive aspergillosis

The transfusion of granulocytes to restore host defenses in severely granulocytopenic patients or in patients with defective granulocyte functions has been studied for more than 60 years. However, inadequate dosage of cells and inconsistent efficacy has limited the usage of these transfusions. Recently, the use of mobilizing agents such as granulocyte colony stimulating factors and dexamethasone has renewed interest in these treatment modalities. The present study is conducted to determine an appropriate method of enriched granulocyte collection with Fresenius AS.TEC.204 cell separator (Fresenius, Bad Homburg, Germany) and to evaluate the preliminary clinical results of granulocyte transfusion therapy in patients with chronic granulomatous disease and invasive Aspergillosis in parallel with in vitro granulocyte function. Three patients who have been treated for chronic granulomatous disease and invasive Aspergillosis received a total of 20 granulocyte transfusions. To mobilize granulocytes, healthy donors were given 450 microg of granulocyte colony-stimulating factor (G-CSF) subcutaneously and 8 mg of dexamethasone orally approximately 12 h before collection. Five microg/kg/day of G-CSF was also subcutaneously administered prior to granulocyte transfusions. The first patient received 4; the second, 14 and the third, 2 transfusions. The granulocyte count given to these patients ranged between 0.4 and 3.0 x 10(9)/kg. Most transfusions were well tolerated. The nitroblue tetrazolium (NBT) tests that were done 16-24 h after the transfusion showed 14-46% dye reduction. Two of the three patients survived the infection. Granulocyte transfusions from G-CSF and dexamethasone stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially with disseminated invasive Aspergillosis.     

Granulocyte concentrate function during preservation: effect of temperature.

Granulocyte concentrates collected from normal donors are necessarily stored for varying intervals up to the time of transfusion. However, information regarding the fate of collected cells and the optimal mode of storage in vitro in the interval between collection and transfusion is far from complete. We studied granulocyte function during preservation of granulocyte concentrates for up to 72 hr. The initial and most consistent alteration in granulocyte function during storage was failure of random migration and chemotaxis after 24 hr of storage (50% and 61% of normal, respectively). By 48 hr the respiratory burst was decreased by 42%, whereas at 48 hr phagocytic and bactericidal activities were nearly normal. Defects in migration and respiratory burst are not due to delayed activation of these functions but to absolute decreases in maximum rates of migration and oxygen consumption. Comparison of granulocyte concentrate storage at 6 degrees C versus room temperature indicated at 24 hr an improved (p greater than 0.02) but still abnormal (p greater than 0.02) chemotactic response with 24 degrees C storage and at 48 hr no difference in migration but a slight advantage in bacterial killing at 6 degrees C storage. These studies show that severe impairment of granulocyte function occurs within 24 hr of collection by centrifugal means; consequently, granulocyte concentrates should be transfused as soon as possible after collection.     

Provision of a Panel of Anti-Toxoplasma-Negative Blood Donors

Toxoplasma gondii has been reported to cause complications only in immunosuppressed patients receiving leucocyte transfusion, when severe acute toxoplasmosis has been reported with associated mortality. At the North London Blood Transfusion Centre (NLBTC) we have screened 392 plasmapheresis donors (using toxoreagent latex agglutination test manufactured by Eiken) to provide a panel of blood donors negative for antibody to toxoplasma for seronegative recipients. A toxoplasma-negative panel of donors would only be required for those rare instances when granulocyte concentrates are indicated for transfusion of seronegative recipients. The toxoreagent test classified the 392 blood donors as 36% positive, 23% weakly reactive and 41% negative; these negative sera were retested with toxoreagent and 17% of them reacted weakly but none were positive. The toxoreagent 'weakly-reactive' sera (all of which were Sabin-Feldman dye test negative) can probably best be accounted for by the exacting screening conditions under which we operated to ensure seronegativity in our special donor panel. 40% of the antibody-positive donors were female and 34% male. Seropositivity increased with age.     

Granulocyte transfusion: revisited

Neutrophils are the immune system's main cellular defense against bacterial and fungal infections. Transfusion of granulocytes has been considered a therapeutic modality for severe bacterial and fungal infections in patients with prolonged neutropenia and with functional neutrophil disorders. Good theoretic and experimental evidence demonstrating granulocyte transfusion efficacy exists in preventing and treating severe infection. However, clinical evidence has been more difficult to interpret, with efficacy equivocal in many studies and further trials hindered by limitations in collecting adequate doses of leukocytes from healthy steroid-mobilized donors. The development and use of granulocyte colony-stimulating factor to stimulate normal donors has generated renewed interest in granulocyte transfusions. In clinical studies, granulocyte colony-stimulating factor has markedly enhanced the yield of leukocytes collected from normal donors, which may improve clinical outcomes in patients with severe infections and neutropenia who receive granulocyte transfusions. Preliminary clinical evidence, when correct granulocyte dose per patient body weight is optimized, suggests efficacy. However, well-designed randomized clinical trials are necessary to definitively establish granulocyte transfusions as a viable therapeutic modality in the treatment of severe bacterial and fungal infections in patients with functional neutrophil disorders or neutropenia.     

Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines

Background and Objectives Transfusion‐related acute lung injury (TRALI) is associated with the passive transfusion of leucocyte antibodies in blood products. Blood Transfusion Services have adopted a number of different strategies for reducing the incidence of TRALI, but, while these have been successful, TRALI has not been completely eliminated. Many Transfusion Services have introduced leucocyte antibody screening of donors to further reduce TRALI. This report describes the results of donor leucocyte antibody screening within NHS Blood and Transplant and the guidelines that have been developed for Transfusion Services within the United Kingdom (UK) to reduce the incidence of TRALI. Materials and Methods Blood samples from newly recruited female apheresis donors were tested for human leucocyte antigens (HLA) class I and class II antibodies and granulocyte‐specific antibodies. Results A total of 1157 female donors were evaluated. Three hundred and fifteen (27·23%) donors had HLA class I or II antibodies and were returned to red cell component donation. Fifty‐seven (6·77%) of the remaining 842 donors were found to have granulocyte‐specific antibodies of which 11 (1·31%) had HNA‐specific antibodies. A total of 818 donors (70·70%) were accepted for platelet apheresis, 336 donors (29·04%) were returned to red cell component donation, and three donors with HNA‐3a antibodies (0·26%) were deferred from therapeutic donation. Conclusions Female donors with leucocyte antibodies were identified in a stratified screening programme. Donors with antibodies were either directed to red cell donation or deferred. This process, combined with other measures that have already been introduced, is anticipated to further reduce the incidence of TRALI.     

Granulocyte transfusion in the G-CSF era

Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of granulocytes delivered. Collection of granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20～30×10⁹ neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8×10¹⁰ cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.     

Granulocyte transfusions: current status

Since granulocyte transfusions first became widely used in clinical medicine, there have been advances in the treatment of acute leukemia and improvement in prevention and management of infection in neutropenic patients. Improved understanding now exists concerning prognosis of infections in such patients, and advances have been made in procurement of granulocytes. Granulocyte transfusions should be given for specific indications, and used adjunctively to other established antiinfective therapy. Once initiated, transfusions should be given in adequate doses at daily intervals (at least) with ongoing evaluation and periodic reassessment of the whole antiinfective program. Serious complications of granulocyte transfusion therapy are relatively rare, but the physician should be prepared to manage them intelligently. Research continues in discerning exactly how granulocyte transfusion work, in preservation of granulocytes, and in delineation of immunologic phenomena affecting the efficiacy of such therapy. Granulocyte transfusions will continue to be important in the management of acute leukemia, and other reversible bone marrow failure states, and in marrow transplantation and autotransplantation.     

Improved prognosis for granulocytopenic patients with gram-negative bacteremia

The grave prognosis associated with gram-negative bacteremia occurring in granulocytopenic patients with cancer suggests that granulocyte transfusions are frequently indicated. We have evaluated 67 episodes of gram-negative bacteremia, studied in four consecutive antibiotic trials, in order to correlate prognostic determinants of recovery. These patients had a median absolute granulocyte count of 100/μl at the time of bacteremia. Empiric antibiotic regimens were begun at the first evidence of suspected infection. Granulocyte transfusions were employed only as clinically indicated by inadequate patient response to antibiotic therapy. Among the 29 patients who had an increase in their granulocyte count of ?100/μl over the subsequent 14 days, 27 (93 per cent) recovered whereas among 38 patients who had no appreciable increase in their granulocyte count, 21 (55 per cent) improved (p = 0.006). In this latter group of patients with no granulocyte recovery, the susceptibility of the pathogen(s) to the initial empiric antibiotic regimen was of major importance. None of four patients responded when the pathogen was resistant to both antibiotics initially utilized, six of 14 (44 per cent) patients responded when there was susceptibility to one antibiotic, and 15 of 20 (75 per cent) patients responded when there was susceptibility to both antibiotics (p < 0.025). We conclude that patients with gramnegative bacteremia and persistent granulocytopenia will often respond to antimicrobial therapy alone provided the initial choice of empiric antibiotics is appropriate and that their use is instituted promptly. Granulocyte transfusions need not be added unless clinical evaluation indicates inadequate response.     

Granulocyte function in elderly patients receiving chemotherapy for aggressive non-Hodgkin's lymphoma. Effect of granulocyte colony-stimulating factor

BACKGROUND: Treatment with granulocyte colony-stimulating factor (G-CSF) is given in order to mitigate chemotherapy-induced granulocytopenia and the risk of infectious complications, which constitute a major threat to elderly patients, in particular, with malignant disorders. The aim of this study was to evaluate whether G-CSF therapy would improve granulocyte defence mechanisms against infectious agents in this elderly, high-risk patient population. METHODS: Fourteen elderly (>60 years) patients with aggressive non-Hodgkin's lymphoma were enrolled in the study. Using flow cytometry we studied the expression of CD11b, before and after stimulation with fMLP, and CD16, as well as granulocyte metabolic activation measured as intracellular accumulation of dichlorofluorescein during induction chemotherapy. Eight patients were randomised to receive G-CSF treatment (5 &mgr;g/kg) on days 2-15. Granulocyte studies were done regularly during one 3-week cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CNOP (doxorubicin substituted by mitoxantrone). RESULTS: Patients receiving G-CSF showed a faster restitution of granulocyte counts. Granulocyte CD11b expression following fMLP stimulation in vitro decreased during G-CSF therapy (P<0.005). A less pronounced (but not significant) reduction in CD16 expression was noted in the G-CSF-treated group. In contrast, fMLP-stimulated metabolic activation did not show consistent changes during the treatment cycle. Two episodes of infections during granulocytopenia that required hospitalisation were observed in each group. CONCLUSIONS: G-CSF treatment efficiently accelerated granulocyte recovery following chemotherapy. This probably compensates for the transient functional aberrations in circulating granulocytes observed in this patient group.     

Donor CMV serostatus has no impact on CMV viremia or disease when prophylactic granulocyte transfusions are given following allogeneic peripheral blood stem cell transplantation

We studied the impact of donor cytomegalovirus (CMV) serologic status on CMV viremia and disease when prophylactic granulocyte colony-stimulating factor (G-CSF)-mobilized granulocyte transfusions (GTs) were given following allogeneic peripheral blood stem cell (AlloPBSC) transplantation. A cohort of 83 patients who received 2 prophylactic GTs from ABO-compatible stem cell donors following AlloPBSC transplantation was compared with a cohort of 142 patients who did not. AlloPBSC donors were eligible for granulocyte donation irrespective of their CMV serostatus. Recipients received no prophylactic therapy for CMV. Donor CMV serostatus had no impact on CMV viremia and disease in the 2 cohorts. Our data show that in an era of effective surveillance and preemptive therapy for CMV, AlloPBSC recipients can safely receive 2 transfusions of prophylactic G-CSF-mobilized granulocyte components from CMV-seropositive AlloPBSC donors. This knowledge may help expand the donor pool in areas with a high prevalence of CMV in the general population.     

Granulocyte growth factors in the treatment of non-small cell lung cancer (NSCLC)

Neutropenia and subsequent infections are common events that limit treatment of non-small cell lung cancer (NSCLC). Granulocyte growth factors (G- and GM-CSF) have been introduced in clinical practice and their use has yielded a reduction of the infection risk related to chemotherapy and a dose increase of drug delivery. Randomized clinical trials have shown that granulocyte colony-stimulating factors and, more recently, the longer-acting pegylated granulocyte colony-stimulating factor (pegfilgrastim) effectively reduce the incidence and severity of neutropenia and of its complications. Recommendations for the use of haematopoietic colony-stimulating factors from the American Society of Clinical Oncology (ASCO) have been published in 1994 and updated in 1996, 1997 and 2000. Recently, moreover, National Comprehensive Cancer Network (NCCN) guidelines for the myeloid growth factors in cancer treatment make available. Chemotherapy-associated myelosuppression is a major limitation of anticancer therapy also in early stage, local advanced and metastatic NSCLC. Recently, dose-dense chemotherapy has been shown to improve the outcome in early stage breast cancer and non-Hodgkin's lymphoma. However, few randomized trials have been reported on chemotherapy with or without granulocyte growth factors as primary prophylaxis in NSCLC. Presently, there is no evidence for a benefit in response rate and survival from the use of granulocyte growth factors as support of chemotherapy, in particular, for locally advanced and metastatic NSCLC. In clinical practice, the role of granulocyte growth factors for NSCLC treatment should be limited following the guidelines. An appropriate use of granulocyte growth factors may reduce the overall cost of treatment and improve the quality of life, important aims in the treatment of patients with local advanced or metastatic NSCLC. In the future, we need to identify patients who can benefit from granulocyte growth factors for optimize the schedule and doses, in advanced disease and also, after the recent positive results of adjuvant chemotherapy, in early stages. This review summarizes the present knowledge on the use of granulocyte growth factors in NSCLC.     

Granulocyte transfusions

Laboratory and clinical studies have demonstrated beyond question that granulocyte transfusions can have a beneficial effect on the incidence and course of bacterial infection. The increment of improved survival produced by granulocyte transfusions depends on the effectiveness of the alternative (primarily antibiotic) therapy alone, and this varies with the pattern of bacterial predominance and sensitivity, which is notoriously changeable. The absolute effectiveness of granulocyte transfusion therapy is influenced by the quality of the transfusions and the immune status of both the recipient and the granulocyte donor. The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged. Severely neutropenic patients with established infection unresponsive to antibiotic therapy are appropriate recipients of granulocyte transfusions. Well-designed programs of prophylactic granulocyte transfusions can reduce the occurrence of bacterial infection in neutropenic patients, but there are few clinical situations in which their use is justified. The use of cytomegalovirus-seropositive granulocyte donors for cytomegalovirus-seronegative recipients should be avoided. There is a need for technical advances that will increase the ease and efficiency of granulocyte procurement.     

Transfusion-related acute lung injury associated with interdonor incompatibility for the neutrophil-specific antigen HNA-1a

BACKGROUND AND OBJECTIVES: A patient transfused with two pooled platelet concentrates became breathless. Bilateral infiltrates were seen on chest X-ray. A diagnosis of transfusion-related acute lung injury (TRALI) was made. The patient received 100% oxygen and recovered after 5 days. MATERIALS AND METHODS: Antibody screening, cross-matching for granulocyte and lymphocyte antibodies and typing for granulocyte antigens was undertaken. RESULTS: The patient typed as HNA-1b/HNA-1b. Granulocyte and lymphocyte antibodies were not detected in the patient's serum or in any of the donor sera by cross-match. In antibody screening against typed panel granulocytes, complement-fixing anti-HNA-1a IgM antibodies were detected in the serum of one female donor. Two of the other donors who contributed to the pooled platelet concentrate containing the HNA-1a IgM antibodies typed as HNA-1a/HNA-1b. CONCLUSION: Anti-HNA-1a IgM antibodies may have formed immune complexes with white cell fragments or soluble FcgammaRIII from HNA-1a+ donors in the pooled platelet concentrate and initiated TRALI.