Transfusion-related Alloimmunization Research Articles

Major reduction in occurrence of anti-c and anti-E in pregnancy after more than 10 years of preventive matched transfusion with most benefit for c-matching.

Extension with cE-matching of the transfusion policy for women under 45 years to prevent alloimmunization and hemolytic disease of the foetus and newborn (HDFN) was evaluated. After implementation of cEK-matching, anti-c occurrence decreased from 46.8 to 30.4 per 100 000 pregnancies (RR 0.65, 95% CI 0.54-0.79), while anti-E occurrence decreased from 122.1 to 89.9 per 100 000 pregnancies (RR 0.74, 95% CI 0.66-0.84). The c-negative women showed a higher anti-E occurrence before cEK-matching and a more pronounced decline with the new policy. This indicates that cEK-matched transfusion effectively reduces alloimmunization, and that a cK-matched approach could prevent most transfusion-related alloimmunization and HDFN.

A retrospective observational study to estimate the risk of HLA alloimmunization with blood transfusion: Can the risk be reduced by leucodepletion?

BackgroundIn this retrospective study, our aim was to find the effect of leucodepleted (LD) blood transfusions on the formation of anti-HLA-antibodies when compared to non-leucodepleted (non-LD) transfusions using Luminex-based method. MethodsIn this study, Luminex single antigen bead assay (L-SAB) and HLA typing were performed on 310 patients. Test positivity rates (as MFI - Mean florescence intensity) were analyzed according to the different sensitization events and gender. ResultsOf the 310 patients included in the study, 58.06% (180) patients were male and 41.93% (130) were female. The average age of the patients was 42.86 (±12.37) years. In this study, test positivity rates were significantly lower in the patients who received LD RBC units than in those who received non-LD RBC units (28.43% = 29 of 102 Vs 55.22% = 74 of 134, p < 0.05). In our study, transfusion combined with a history of pregnancy had higher number of significant HLA antibodies compared to cases where transfusion was the only sensitization event (81.81% = 18/22 Vs 39.71% = 85/214, p < 0.05). In addition, anti-HLA-antibodies-MFI were significantly (p < 0.01) higher in non-LD patients compared to LD patients. ConclusionPatients who received LD RBC units had a significantly lower rate of transfusion-associated alloimmunization compared to those who received non-LD RBC units. Multiparous women had a high risk for transfusion-related alloimmunization compared to both nulliparous women and male patient. Furthermore, class I-anti-HLA-antibodies (HLA-B and HLA-A + B) were significantly associated with pregnancy sensitization and/or blood transfusion as a single sensitization.

Red Blood Cell Alloimmunization and Autoimmunization in Blood Transfusion-Dependent Sickle Cell Disease and β-Thalassemia Patients in Al-Ahsa Region, Saudi Arabia.

The risk of developing transfusion-related complications, especially alloimmunization, is an ongoing concern for transfusion-dependent patients. It is important to determine the rate of alloimmunization and autoimmunization in Al-Ahsa Region, Saudi Arabia, where sickle cell disease (SCD) and thalassemia incidence rates are the highest in Saudi Arabia. A cross-sectional study was conducted to review the transfusion history of patients with SCD and thalassemia at the King Fahad Hospital (KFH) in Al-Ahsa, Saudi Arabia. 364 transfusion-dependent patients were included in this study. Alloimmunization rates in patients with SCD and thalassemia were 16.7% and 11.97%, respectively, while autoimmunization rates in patients with SCD and thalassemia were 5.3% and 0.7%, respectively. The most frequent alloantibodies among the study participants were against Kell, Rh blood group systems. Blood transfusion-related alloimmunization and autoimmunization compromise the proper management of chronically transfused patients. Ideally, extended matched phenotyping should be implemented to prevent alloimmunization and reduce the risk of developing blood transfusion-related alloantibodies.

Transfusion-Related Alloimmunization to Red Blood Cell Antigens in Japanese Pediatric Recipients.

Red blood cell (RBC) transfusion to neonates is thought to rarely provoke an immune response. Neonatal testing guidelines suggest that antibody screening is not necessary when the mother has no antibodies. Alternatively, maternal blood samples can be used for antibody screening and cross-matching. However, the guidelines are based on small-scale studies of white-dominant populations. Furthermore, transfusion-related alloimmunization is less well established among children and adolescents as a whole among Japanese and East Asians. To elucidate the incidence of transfusion-related alloimmunization among neonates, children, and adolescents, and whether current guidelines are applicable to Japanese populations, a nationwide retrospective multicenter cohort survey was conducted in 50 tertiary-care hospitals in Japan. Between 2001 and 2015 inclusive, recipients of at least 1 allogeneic RBC transfusion were categorized into groups A-F according to their age at the time of transfusion: (A) neonates <1 month; (B) infants 1 to <12 months; (C) children 1 to <5 years; (D) prepubescents 5 to <10 years; (E) young pubescents 10 to <15 years; and (F) adolescents/young adults 15 to <20 years. Excluding maternally derived antibodies and naturally occurring, cold-reactive, and/or nonspecific antibodies, 69 (0.61%) of 11350 RBC recipients <20 years old formed at least 1 clinically significant alloantibody. The alloimmunization rate differed significantly (P < .0001) by age: none (0%) of 3407 in group A; 11 (0.46%) of 2410 in group B; 18 (0.76%) of 2361 in group C; 9 (0.80%) of 1119 in group D; 12 (1.15%) of 1043 in group E; and 19 (1.88%) of 1010 in group F. Clearly different incidences of alloimmunization emerged in group A compared to B, C, D, E, or F, as confirmed by logistic regression analysis adjusted by numbers of donor exposure. Alloimmunization did not occur from RBC transfusions within the first month of life and rarely occurred (0.46%-0.80%) after transfusion within the first decade of life. Alloimmunization occurred in 1.15%-1.88% of young pubescents and adolescents/young adults. These findings support the use of guidelines developed in Europe and the United States for East Asian pediatric recipients.

Genetic Association Studies of Red Blood Cell Transfusion Related Alloimmunization: A Systematic Review and Meta-Analysis

Introduction: Blood transfusions are an important treatment modality for patients with either acute or chronic onset anemia such as trauma, sickle cell disease, and hematological malignancies. Transfusion poses a risk for alloimmunization, which may lead to potentially lethal transfusion reactions. A promising strategy to prevent alloimmunization is extensive matching on blood groups, yet this is a costly procedure and should be reserved for patients at highest risk for alloimmunization. Identification of genetic variants that increase the risk for alloimmunization might help to identify high-risk patients and could be used as a screening tool for patients receiving multiple transfusions. Objectives: To summarize all available evidence on genetic risk factors for alloimmunization after blood transfusion. Design: Systematic review with meta-analysis of observational studies. Studies were only included in the meta-analysis if polymorphisms were tested at least 3 times, and if ethnic background of the population and the control populations were comparable between studies. Data sources: The online databases Embase, MEDLINE and the Cochrane Library were search for relevant articles with search terms: 1) transfusion, 2) alloimmunization 3) genetics. The search was last updated March 2018. Eligibility criteria: 1) Primary study that assessed the association of genetic polymorphisms with transfusion related alloimmunization, 2) a human population, 3) studies with at least 50 patients, 4) full text availability. Data extraction: Two reviewers independently screened articles for eligibility, extracted data using a standardized data extraction form. Extracted data included study setting, study population, participant demographics, baseline characteristics, study methodology, comparisons and outcome, and risk of bias. Primary outcome measure: Alloimmunization after one or more blood transfusions. Risk of bias assessment: The quality of the included studies was assessed by the Q-genie tool for genetic association studies. Results: A total of 2045 cases and 24084 controls were derived from 18 genetic case-control studies that were included in this systematic review. Most commonly studied disease group was sickle cell disease (SCD) (8 studies). Three studies included patients with different diseases and seven studies did not report the underlying disease. Eleven studies identified the association of HLA polymorphisms with alloimmunization and 8 studies focused on non-HLA variants. Overall quality of the included studies was moderate (11 studies), 2 studies were of high quality, and 5 studies were ranked as poor. HLA-DRB1*04 (Odds Ratio 7.16, 95%CI 3.87-13.22, P&lt;0.00001) and HLA-DRB1*15 (OR 3.01, 95%CI 1.84-5.53, P&lt;0.0001) were by meta-analysis significantly associated with anti-Fy(a) formation, although there was considerable heterogeneity (I2=78% and 55% respectively). Moreover, HLA-DRB1*10 (OR 2.64, 95%CI 1.41-4.95, P=0.002), HLA*DRB1*11 (OR 2.11, 95%CI 1.34-3.32, P=0.001), and HLA-DRB1*13 (OR 1.71, 95%CI 1.26-2.33, P=0.0006) were overall associated with anti-Kell formation. Heterogeneity was less prominent with an I2 of 0%, 54% and 19% respectively (Figure 1). No other variants were eligible for meta-analysis. Non-HLA variants were tested less extensively, as most variants were reported by only 1 study. Polymorphisms of genes in the immunomodulatory pathways were assessed most frequently. Of these variants, FC-gamma-receptor 2C.nc-ORF was associated with a decreased risk of alloimmunization in SCD (OR 0.26, 95%CI 0.11-0.64, p=0.003). All other associations that were described as significant by the original articles were summarized in Figure 2. Discussion: There is limited evidence supporting the role of genetic risk factors for alloimmunization. The results of our meta-analysis suggest that several HLA polymorphisms potentially influence antigen presentation of the Duffy(a) and Kell antigen. Once confirmed by experimental studies, these polymorphisms could be used as a screening tool for the prevention of alloimmunization among frequently transfused patients. Overall, the effect of genetic variants on alloimmunization has mostly been assessed by small studies, hampering reliable interpretation of the results. Future studies should include large and well-defined cohorts when performing genetic analysis on this complicated subject. Disclosures No relevant conflicts of interest to declare.

Transfusion-related alloimmunization to red cell antigens among pediatric recipients

Aims: Alloimmune response to red cell transfusion has not been widely investigated in pediatric patients. We retrospectively compared the frequency and specificity of red cell antibody formation among pediatric recipients grouped by age, versus an adult control cohort. Methods: A total of 331 pediatric red cell transfusion recipients were studied in four age groups: 0 to 4.9 months (Group A), 5.0 to 11.9 months (Group B), 1.0 to 5.9 years (Group C), and 6.0 to 14.9 years (Group D). Similarly transfused adult males, 20.0 to 59.9 years old, as a control cohort group. Alloimmunization was defined as post-transfusion detection of red cell alloantibodies not detected prior to transfusion. Results: After red cell transfusion, no one in Group A (0 of 106) developed alloantibodies, whereas 8.0% (2 of 25) in Group B, 1.1% (1 of 95) in Group C, and 2.9% (3 of 105) in Group D, versus 2.1% (8 of 380) of adult male controls who developed alloantibodies. However, these differences did not achieve statistical significance. Conclusion: This investigation of alloimmunization in pediatric recipients found no cases in patients younger than five months old, however, the incidence rates of older age groups were statistically indistinguishable from a control cohort of male adults. Until larger studies suggest otherwise, current antibody screening and cross-matching policies should be continued.

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Transfusion-related alloimmunization is a potent barrier to the engraftment of allogeneic hematopoietic stem cells in patients with nonmalignant diseases (NMDs). Memory T cells, which drive alloimmunization, are relatively resistant to commonly used conditioning agents. Alefacept, a recombinant leukocyte function antigen-3/IgG1 fusion protein, targets CD2 and selectively depletes memory versus naive T cells. Three multiply transfused pediatric patients with NMD received a short course of high-dose i.v. alefacept (.25 mg/kg/dose on days −40 and −9 and .5 mg/kg/dose on days −33, −26, −19, and −12) before undergoing unrelated allogeneic transplant in the setting of reduced-intensity pretransplant conditioning and calcineurin inhibitor–based post-transplant graft-versus-host disease (GVHD) prophylaxis. Alefacept infusions were well tolerated in all patients. Peripheral blood flow cytometry was performed at baseline and during and after alefacept treatment. As expected, after the 5 weekly alefacept doses, each patient demonstrated selective loss of CD2hi/CCR7−/CD45RA− effector memory (Tem) and CD2hi/CCR7+/CD45RA− central memory (Tcm) CD4+ and CD8+ T cells with relative preservation of the CD2lo Tem and Tcm subpopulations. In addition, depletion of CD2+ natural killer (NK) cells also occurred. Neutrophil recovery was rapid, and all 3 patients had 100% sorted (CD3/CD33) peripheral blood donor chimerism by day +100. Immune reconstitution (by absolute neutrophil, monocyte, and lymphocyte counts) was comparable with a cohort of historical control patients. All 3 patients developed GVHD but are all now off immune suppression and >2 years post-transplant with stable full-donor engraftment. These results suggest that alefacept at higher dosing can deplete both memory T cells and NK cells and that incorporating CD2-targeted depletion into a reduced-intensity transplant regimen is feasible and safe in heavily transfused patients.

Red blood cell transfusions are associated with HLA class I but not H-Y alloantibodies in children with sickle cell disease.

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion-related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion-related alloimmunization to minor histocompatibility antigens (mHA), such as H-Y antigens, has not been clinically characterized. We conducted a cross-sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H-Y antigens and to HLA class I and class II. Few patients had H-Y antibodies, with no significant differences in the prevalence of any H-Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P=0·046; class II: 7% vs. 8%, P=0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1-22·3). These results are consistent with immunological responder and non-responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion-related alloimmunization.

Chronic Inflammatory Autoimmune Disorders Are a Risk Factor for Blood Group Alloimmunization in Transfused Patients

Background: Alloimmunization to red blood cell (RBC) antigens is a clinically-significant problem, but the mechanisms underlying antibody induction remain poorly understood. Data from murine models has suggested that inflammation can promote blood group alloimmunization. To our knowledge, only one group (Ramsey & Smietana, Transfusion 1995;35:582) has examined the influence of inflammation on RBC alloimmunization; however, study subjects were predominantly female, making it difficult to determine the contribution of inflammation towards transfusion-related alloimmunization. Thus, the aim of our study was to examine whether inflammation associated with chronic autoimmune disorders increases the risk for development of transfusion-related RBC alloantibodies in a primarily male patient cohort.Methods: The transfusion records of alloimmunized patients at a Veterans’ Affairs facility were extracted from a large database of individuals who underwent type and screen testing from 1961 through May, 2014. For alloimmunized patients, the following information was retrospectively collected: 1) demographic data including gender, 2) the number and specificity of alloantibodies reactive at 37°C and/or antihuman globulin phase, and 3) the presence of an underlying chronic inflammatory autoimmune disorder (and the specific diagnosis, as applicable). In addition, the records of 250 randomly-selected patients undergoing RBC administration were reviewed to establish the transfusion rate among individuals with chronic inflammatory autoimmune disorders.Results: Among all patients undergoing type and screen testing at our facility, 220 had one or more detectable alloantibodies. Patients with a chronic inflammatory autoimmune disorder constituted nearly 16% (35/220) of total alloimmunized individuals. These patients formed 50 total alloantibodies (1.4 antibodies per alloimmunized patient). Anti-D (n=10) and anti-K (n=10) were the two most common alloantibodies detected in this group, followed by anti-E (n=8) and anti-C (n=6). Men represented about 86% (30/35) of alloimmunized patients with an autoimmune disorder, indicating that the vast majority of detected antibodies resulted from transfusion rather than pregnancy. The most common autoimmune disorder among alloimmunized patients was psoriasis (9/33; 27%), followed by rheumatoid arthritis (6/33; 18%). Examination of the charts of randomly-selected patients who underwent RBC transfusion showed that 8.4% (21/250) had an underlying chronic inflammatory disorder. The ratio of alloimmunized patients with an autoimmune disease to those without one was significantly different than the ratio of transfused patients with an autoimmune disease to those without one (P=0.012, chi square test; P=0.018, chi square test with Yates’ correction for continuity).Conclusions: Patients with autoimmune diseases represented a substantial portion of individuals with transfusion-associated alloantibodies. Patients with chronic inflammatory disorders formed alloantibodies at nearly double the rate at which they were transfused. As such, precautionary interventions (e.g., extended phenotypic matching for K, E, and C antigens) may be warranted for patients with chronic inflammatory disorders. DisclosuresNo relevant conflicts of interest to declare.

Transfusion Related Alloimmunization In Children: Epidemiology and Effects Of Chemotherapy (TRACE-EC Study)

IntroductionPediatric hematology/oncology patients require numerous transfusions during myelosuppressive chemotherapy which may lead to red cell (RC) alloantibody formation. However, transfusion related alloimmunization in children has not been studied except in the neonatal and hemoglobinopathy populations. Variability of RC alloimmunization rates by cancer diagnosis has not been described and the immunosuppressive effect of chemotherapy on alloimmunization is unknown. One study has shown a reduction in IgM and IgG in pediatric leukemia patients receiving chemotherapy (Martín Ibáñez et al Allergol Immunopathol 2003); hence, one could hypothesize that chemotherapy could suppress the alloimmune response. This study aimed to: 1) report the rate of alloimmunization in children receiving RC transfusions, 2) compare these rates between oncology and non-oncology patients, and 3) compare these rates based on cancer diagnosis and stage. MethodsTRACE-EC was a retrospective observational study using a large database containing patient blood utilization information from 3 academic hospitals. Patient inclusion criteria included: age ≥ 4 months and ≤ 17 years old at the time of receiving ³ 1 non-autologous RC transfusion between April 2002 and November 2011. Diagnoses were identified using ICD10 codes. Patients with immune disorders were excluded. Study patient cohort included patients with malignancies and recipients of hematopoietic stem cell transplant (HSCT) to treat a malignancy; control cohort included non-oncology patients who met the inclusion criteria. Patient and blood utilization data were extracted from the database, and chemotherapy data were obtained by retrospective review of patient medical records. Study patients were stratified for analysis based on cancer diagnosis and stage (surrogate for chemotherapy intensity). Cancer stage was categorized as low level (I, II, standard risk) and high level (III, IV, V, high risk). Control patients with hemoglobinopathy were analyzed separately due to their high alloimmunization rate (Aygun et al. Transfusion 2002). ResultsThere were 1253 patients in the study: 944 in control group; 309 in study group. Females made up 49% of control group and 43% of study group. Mean age was 8.6 years (SD 6.4) in control group, and 7.2 years (SD 5.5) in study group. The frequency of alloimmunization and RC utilization by diagnosis in control and study groups is summarized in Table 1. Overall, a statistical difference in the frequency of alloimmunization was not demonstrated between control patients (4.3%) and study patients (5.5%), p=0.40. When hemoglobinopathy patients were removed from the control group, frequency of alloimmunization decreased to 3.8% (p=0.19). Alloimmunization occurred in 5.4% (10/186) and 5.7% (7/123) of patients with a high level and low level cancer stage respectively, p=0.91. HSCT recipients had a higher rate of alloimmunization than non-HSCT but this was not statistically significant (11.4% vs. 4.5% respectively, p=0.07). Alloimmunization occurred in 4.9% of patients with hematologic malignancies and 7.1% of patients with solid tumors (p=0.44).Table 1Frequency of alloimmunization in control and study group by diagnosis.# patientsTotal # RC transfusions# transfusions/patientMedian (Q1-Q3)# days with transfusion/patientMedian (Q1-Q3)# patients with allo-antibodies (%)CONTROL GROUPThalassemia17160039 (5-132)38 (3-90)3 (17.6)Sickle Cell Disease232383 (1-11)2 (1-9)4 (17.4)Aplastic Anemia375175 (2-10)4 (1-8)2 (5.4)Other86736032 (1-4)1 (1-2)32 (3.7)Overall94459582 (1-5)1 (1-3)41 (4.3)Overall excluding hemoglobino-pathy90441202 (1-4)1 (1-2)34 (3.8)STUDY GROUPHematologic Malignancies22522777 (4-13)5 (3-10)11 (4.9)Solid Tumors8410759 (4-20)9 (4-15)6 (7.1)HSCT4471115 (7-25)10 (6-18)5 (11.4)Non-HSCT26526417 (4-13)5 (3-10)12 (4.5)Overall30933527 (4-15)6 (4-11)17 (5.5) ConclusionsThis is the first study that has looked at the frequency of alloimmunization in transfused pediatric patients by diagnostic category and cancer stage. The study confirmed high alloimmunization rates in hemoglobinopathy patients. No difference in the frequency of alloimmunization was observed based on cancer diagnosis, stage, or HSCT status. Further studies are needed to assess the effect on alloimmunization of the high RC utilization rate shown in cancer patients and HSCT recipients. Disclosures:Heddle:Health Canada: Research Funding; Canadian Blood Services: Membership on an entity's Board of Directors or advisory committees, Research Funding; CIHR: Research Funding.

Molecular analysis of a patient with type I Glanzmann thrombasthenia and clinical impact of the presence of anti-αIIbβ3 alloantibodies

The occurrence of transfusion-related alloimmunization against αIIbβ3 is a major concern in patients with Glanzmann thrombasthenia (GT). However, few data are available about molecular defects of GT patients with anti-αIIbβ3 alloantibodies as well as clinical impact of these antibodies on platelet transfusion. Here, we report a case of type I GT with anti-HLA and anti-αIIbβ3 alloantibodies, who underwent laparoscopic total gastrectomy due to gastric cancer. We found a novel β3 nonsense mutation, 892C > T (Arg272X), and the patient was homozygous for the mutation. Laparoscopic gastrectomy was successfully performed with continuous infusion of HLA-matched platelet concentrates and bolus injection of recombinant factor VIIa at 2 h intervals. Total bleeding was 370 mL and no red-cell transfusion was necessary. Flow cytometric analysis employing anti-αIIbβ3 monoclonal antibody revealed that the transfused platelet count was maintained around 20-30 × 10⁹/L during the operation and 10 × 10⁹/L on the following day. Flow cytometric analysis also showed that transfused platelets retained normal reactivity to ADP stimulation. These results indicate that flow cytometry is useful to assess survival and function of transfused platelets in GT patients with anti-αIIbβ3 antibodies.

Erythrocyte Alloimmunization Analyzed by Gender and Transfusion Status

AbstractAbstract 4407(Purpose) Prior investigations have looked for trends and patterns in post-transfusion erythrocyte alloantibody formation (e.g., Walker et al., Tormey et al., and Hoeltge et al.). While anti-E has consistently been one of the most frequently observed alloantibodies following transfusion, the relative frequency of other antibodies is variably reported. In fact, some authors have reported no relationship between transfusion and alloantibody prevalence (Coles et al. and Domen et al.). Different outcomes might be attributed to antibody detection methods, cohort size, and cohort composition by race (including differences in the racial composition of donor and patient populations). As yet, the significance of gender has not been explicitly investigated in a large cohort of transfused vs. non-transfused patients. This study reports gender differences in erythrocyte alloantibody formation in a nation where blood donor and patient populations are phenotypically similar and relatively homogeneous. (Methods) In response to an open invitation made in November, 2008, 25 Japanese institutions contributed data on 248,785 patients (male:female=1:1.19). Each institution reported results from the previous 3 years. Patients known to have been transfused were placed in the transfused group, whereas patients known not to have been transfused were placed in the non-transfused group. Patients for whom transfusion history was uncertain were excluded. Erythrocyte alloantibodies against D, C, c, E, e, f, Ce, P1, M, N, S, s, Mia, Lea, Leb, Jka, Jkb, Jk3, Fya, Fyb, K, k, Kpa, Kpb, Jsa, Jsb, Dia, Dib, Lua, Lub, Xga and H were analyzed. A patient investigated multiple times was counted as one case. Multiple antibodies in one patient were separately summarized. Antibody incidence was calculated as the percentage of patients in each group with the corresponding antibody. (Results) Erythrocyte antibodies were detected in 3,554 patients (1.43% of all patients, 1.32% of males and 1.52% of females). Including 655 patients with antibodies reported by four more institutions, a total of 4,219 patients with at least one antibody were analyzed. From these, anti-E was observed in 34.7% and 41.3% of male and female transfused patients vs. 8.0% and 21.9% in those not transfused, respectively. Anti-Dia was observed in 3.5% and 4.8% of male and female transfused patients vs. 2.7% and 2.8% in those not transfused. Jka was observed in 2.6% and 4.7% of male and female transfused patients vs. 0.4% and 0.1% in those not transfused. Anti-E+c was observed in 6.6% and 8.4% of male and female transfused patients vs. 0.4% and 2.3% in those not transfused. Emergence of anti-E, anti-Dia and anti-Jka following transfusion was significantly different between males and females (p<0.05, p<0.05 and p<0.01, respectively). (Conclusion) The frequencies of anti-E, anti-Dia, anti-Jka and others depend not only on transfusion history, but also gender. Discordance with other studies suggests that population genetics may also be relevant. These are especially important results in the emerging era of personalized medicine. Hematologists should continue large-scale investigations of transfusion-related alloimmunization to elucidate contributory factors and to optimize patient care.Table 1Erythrocyte alloantibody formation analyzed by gender and transfusion historyantibodytotal(%)male (%)female (%)no transfusionprevious transfusionmale (%)female (%)male (%)female (%)E26.522.229.78.021.934.741.3Lea25.730.721.941.225.516.910.2P110.610.810.523.919.95.55.5M6.25.36.85.37.03.23.3E+c4.13.34.70.42.36.68.4Fyb3.75.02.84.42.34.81.6Dia3.33.43.22.72.83.54.8Leb3.03.22.84.42.42.22.3D1.60.62.40.22.80.81.3Jka1.41.31.40.40.12.64.7C+e1.31.21.40.40.91.82.7others12.613.012.48.712.117.413.9total patients4,2191,8012,418452748651640 Disclosures:No relevant conflicts of interest to declare.

The persistence and evanescence of blood group alloantibodies in men

Non-ABO blood group (BG) alloantibodies can disappear over time, confounding compatibility testing and predisposing patients to delayed hemolytic transfusion reactions. The goal of this study was to analyze BG antibody disappearance after transfusion-related alloimmunization in men. The transfusion service records of 18,750 military veterans at a Department of Veterans Affairs (VA) medical center were screened to identify male patients with one or more BG alloantibodies and who had at least one type and screen performed after initial antibody detection (n = 304). Antibodies were categorized as to whether they were present at a patient's first antibody screening test ("preexisting") or after initial negative testing ("hospital-acquired"). Overall, the evanescence of hospital-acquired antibodies (108/222; 48.6%) was significantly higher (p < 0.0001) than that of preexisting antibodies (36/185; 19.5%). Half (54/108) of evanescent, hospital-acquired alloantibodies disappeared within 6 months of detection, and all disappeared by 10 years. Evanescence of hospital-acquired antibodies was dependent on duration of follow-up testing, because antibodies tested 5 or more years after initial development demonstrated the highest evanescence rate (35/55; 64%; p < 0.01). Some evanescent antibodies (9/407; 2.2% of total antibodies) disappeared and reappeared one or more times without known antigenic reexposure ("multiple evanescence"). Among commonly observed alloantibodies, disappearance varied with antigenic specificity. Approximately two-thirds of BG alloantibodies disappeared within 5 years of induction, a rate higher than previously reported in mixed-sex populations. Evanescence did not appear to be a random, first-order decay process, as evidenced by the lower evanescence rate of preexisting antibodies.

Universal leukoreduction of cellular blood components in 2001? No.

Leukocytes are known to have a number of biologic effects associated with allogeneic blood transfusion ❚Table 1❚. The potential clinical importance of these effects, which are the focus of current debate over the merits of “universal” leukocyte reduction (leukoreduction; cellular components with <5 × 106 leukocytes) include the following: febrile-associated transfusion reactions (FATRs), transfusion-related alloimmunization to platelets, and transfusion-related immunomodulation. Several recent reviews1,2 of this topic, along with commentaries3-6 about the use of leukocytedepleted blood components, have been published. The Blood Products Advisory Committee (BPAC) to the US Food and Drug Administration (FDA) voted 13-0 on September 18, 1998, in favor of universal leukoreduction of blood components,7 but the minutes stated that many committee members agreed there were insufficient good studies, and everyone wanted more data.8 To date, both leukoreduced and nonleukoreduced blood components remain FDA-approved. This commentary will summarize my view of this controversy and the need for additional controlled clinical trials to provide data to resolve this issue. ❚Table 2❚ summarizes the percentage of blood components transfused that were leukoreduced in the United States in 1994 and 1997. The percentages for RBCs (17.6% and 18.3%) and platelets (16.5% and 15.5%) remained static, despite commercial advertisements to clinicians about leukocyte-depletion filters during this period.9 For the first 9 months of 1999, 3,592 (13%) of 27,663 RBC units transfused at our hospital were leukoreduced; our indications for leukoreduction reflect those published previously,4 and are summarized in ❚Table 3❚. FATRs occur in only 0.5% of RBC transfusions; of these, 18% and 8% of patients experience a second or third FATR.10 Approximately 18% of platelet transfusions are

Suppression of transfusion-related alloimmunization in intensively treated cancer patients

A retrospective review of HLA antibody testing and transfusion records of 100 cancer patients who required extensive platelet support revealed that 27 of 100 patients exhibited positive HLA antibody tests; only 13 remained positive on repetitive examination, while 88% of aplastic anemia patients so tested were positive. Sixty-five patients with leukemia, 16 with Ewing's sarcoma, and 19 with recurrent undifferentiated lymphoma were studied. Each patient received at least 10 U of platelets (mean of 72). HLA antibodies were detected in 31% (20/65) of the leukemias, 12% (2/16) of the Ewing's, and 26% (5/19) of the lymphoma patients. Fourteen of the 27 patients who developed antibodies became antibody negative again within 2 mo and remained so. There were no significant differences in quantity of platelet transfusions between antibody-negative patients and alloimmunized patients. A smaller group (n = 8) of aplastic anemia patients followed at the NCl exhibited a frequency of alloimmunization of 88% (7/8) after a mean of 44 U of platelets were transfused. Granulocyte transfusions given therapeutically for granulocytopenia and documented infection did not appear to influence HLA antibody formation. These data indicate that significant immunosuppression occurs in intensively treated cancer patients, as measured by their ability to from antibodies to HLA antigens expressed on the surface of transfused platelets.

Suppression of Transfusion-Related Alloimmunization in Intensively Treated Cancer Patients

A retrospective review of HLA antibody testing and transfusion records of 100 cancer patients who required extensive platelet support revealed that 27 of 100 patients exhibited positive HLA antibody tests; only 13 remained positive on repetitive examination, while 88% of aplastic anemia patients so tested were positive. Sixty-five patients with leukemia, 16 with Ewing's sarcoma, and 19 with recurrent undifferentiated lymphoma were studied. Each patient received at least 10 U of platelets (mean of 72). HLA antibodies were detected in 31% (20/65) of the leukemias, 12% (2/16) of the Ewing's, and 26% (5/19) of the lymphoma patients. Fourteen of the 27 patients who developed antibodies became antibody negative again within 2 mo and remained so. There were no significant differences in quantity of platelet transfusions between antibody-negative patients and alloimmunized patients. A smaller group (n = 8) of aplastic anemia patients followed at the NCl exhibited a frequency of alloimmunization of 88% (7/8) after a mean of 44 U of platelets were transfused. Granulocyte transfusions given therapeutically for granulocytopenia and documented infection did not appear to influence HLA antibody formation. These data indicate that significant immunosuppression occurs in intensively treated cancer patients, as measured by their ability to from antibodies to HLA antigens expressed on the surface of transfused platelets.