Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation.

The use of anti-thymocyte globulin (ATG) has represented the standard of care in graft-versus-host disease (GVHD) prophylaxis in patients undergoing a mismatched unrelated donor (MMUD) transplant. The safety and feasibility of posttransplant cyclophosphamide (PTCY) in this setting have been reported recently, but no study has compared the outcomes of PTCY vs ATG in 9/10 MMUD transplants. Using the registry data of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we performed a matched-pair analysis comparing those 2 strategies in a 9/10 MMUD setting. Ninety-three patients receiving PTCY were matched with 179 patients receiving ATG. A significantly lower incidence of severe acute GVHD was observed with PTCY compared with ATG. Recipients of the former also showed higher leukemia-free survival and GVHD/relapse-free survival (GRFS). When performing a subgroup analysis including patients receiving peripheral blood stem cells, being in complete remission, or receiving the same associated immunosuppressive agents, superiority of PTCY over ATG was confirmed. Similar to the haploidentical setting, use of PTCY is an effective anti-GVHD prophylaxis in the 9/10 MMUD transplant. Use of PTCY may also provide better outcomes in long-term disease control. These results need confirmation in large prospective randomized trials.

Hospital-based transfusion error tracking from 2005 to 2010: identifying the key errors threatening patient transfusion safety.

BACKGROUND: This report provides a comprehensive analysis of transfusion errors occurring at a large teaching hospital and aims to determine key errors that are threatening transfusion safety, despite implementation of safety measures. STUDY DESIGN AND METHODS: Errors were prospectively identified from 2005 to 2010. Error data were coded on a secure online database called the Transfusion Error Surveillance System. Errors were defined as any deviation from established standard operating procedures. Errors were identified by clinical and laboratory staff. Denominator data for volume of activity were used to calculate rates. RESULTS: A total of 15,134 errors were reported with a median number of 215 errors per month (range, 85-334). Overall, 9083 (60%) errors occurred on the transfusion service and 6051 (40%) on the clinical services. In total, 23 errors resulted in patient harm: 21 of these errors occurred on the clinical services and two in the transfusion service. Of the 23 harm events, 21 involved inappropriate use of blood. Errors with no harm were 657 times more common than events that caused harm. The most common high-severity clinical errors were sample labeling (37.5%) and inappropriate ordering of blood (28.8%). The most common high-severity error in the transfusion service was sample accepted despite not meeting acceptance criteria (18.3%). The cost of product and component loss due to errors was $593,337. CONCLUSION: Errors occurred at every point in the transfusion process, with the greatest potential risk of patient harm resulting from inappropriate ordering of blood products and errors in sample labeling.

Record fragmentation due to transfusion at multiple health care facilities: a risk factor for delayed hemolytic transfusion reactions.

BACKGROUND: Patients transfused at more than one health care facility face safety risks, because their transfusion record is fragmented. Blood group antibodies documented at one facility may be unknown to others. Because many antibodies are evanescent, access to prior antibody records is important for preventing incompatible transfusions and delayed hemolytic reactions. The study goal was to quantify multisite transfusion activity and its impact on antibody record accuracy. STUDY DESIGN AND METHODS: Patients (n = 100) undergoing hospital transfusion testing were surveyed to determine the locations and dates of any prior transfusions. Also, transfusion records were examined to determine whether patients (n = 200) known to be alloimmunized at one hospital had antibody testing done at another nearby hospital and, if so, how often the results were discrepant. RESULTS: Twenty-three percent (23/100) of patients undergoing type-and-screen testing reported receiving transfusions at 24 other facilities. Locations of transfusions that occurred elsewhere were 54.2% (13/24) at eight other in-state hospitals, 12.5% in bordering states, 20.8% in more distant states, and 12.5% during military service. Twenty-one percent (42/200) of patients known to be alloimmunized at one hospital had antibody test results on record at another nearby hospital. Antibody discrepancies were noted in 64.3% (27/42) of cases. The most common discrepancy was the failure of one facility to detect an antibody. CONCLUSION: Multisite transfusions were common. For patients seen at both of two nearby hospitals, antibody records were frequently discrepant. The findings support the need for interfacility sharing of transfusion records, particularly at the regional level.

Unmanipulated HLA-mismatched/haploidentical peripheral blood stem cell transplantation for high-risk hematologic malignancies.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high-risk hematologic patients due to the absence of HLA-matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies. STUDY DESIGN AND METHODS: Patients who underwent unmanipulated HLA-mismatched/haploidentical PBSCT from July 2007 to March 2010 with high-risk hematologic malignancies were enrolled for retrospective analysis. RESULTS: Twenty-one patients with high-risk hematologic malignancies underwent unmanipulated HLA-mismatched/haploidentical PBSCT with myeloablative conditioning. The numbers of CD34+ cells infused at transplantation were 4.81 (range, 2.61-11.47)×10(6)/kg. Patients achieved myeloid and platelet engraftment at a median of 16.5 and 20 days, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) on Day 100 was 52.7±10.7%, and the 2-year cumulative incidence of chronic GVHD was 39.5±10.6%. The cumulative incidences of cytomegalovirus antigenemia and hemorrhagic cystitis within 100 days after PBSCT were 59.5±16.7 and 34.8±13.3%, respectively. One hundred-day transplantation-related mortality (TRM) rate and the 2-year cumulative TRM rate were 14.3 and 20.5±7.8%, respectively. The 2-year cumulative overall survival was 62.1±11.4% and the probability of disease-free survival at 2 years was 55.6±10.7% with a 16-month median follow-up. CONCLUSION: Unmanipulated PBSCT is a promising protocol in HLA-mismatched/haploidentical transplant settings.

Antibody development in pediatric sickle cell patients undergoing erythrocytapheresis.

BACKGROUND: Erythrocytapheresis, or red blood cell exchange transfusion (RBCX), with donor red blood cell (RBC) units is now increasingly used in the treatment of acute and chronic complications of sickle cell disease (SCD). As in all transfusions, RCBX carries a risk of immunization against foreign antigen on transfused cells. However, by selecting donor units with RBC phenotypes similar to the patient, the risk of allo- and autoimmunization can be reduced. PROCEDURE: The formation of RBC alloantibodies and/or autoantibodies in 32 multitransfused pediatric SCD patients undergoing monthly RBCX over a 11-year period (12/1998 to 12/2009) was evaluated utilizing a retrospective patient chart review at Kosair Children's Hospital, Louisville, Kentucky. RESULTS: After starting C, E, K antigen-matched RBCX, the rate of clinically significant allo-immunization decreased from 0.189/100 to 0.053/100 U, with a relative risk of 27.9%. Likewise, the rate of autoimmunization decreased from 0.063/100 to 0.035/100 U, with a relative risk of 55.9%. CONCLUSION: After controlling for clinically insignificant antibodies, our auto- and alloimmunization rate was much less than previously reported values. In addition, the incidence of clinically significant allo- and autoimmunization decreased in our patient population after starting minor antigen-matched RBCX. These results suggest that by matching selected RBC phenotypes, there may be an association in the risk of allo- and autoimmunization of multi-transfused SCD patients.

Impact of ABO mismatching on the outcomes of allogeneic related and unrelated blood and marrow stem cell transplantations for hematologic malignancies: IPD-based meta-analysis of cohort studies.

BACKGROUND: The impact of donor-recipient ABO matching on outcomes after allogeneic stem cell transplantation has been a matter of controversy. STUDY DESIGN AND METHODS: Individual patient data-based meta-analysis was conducted with a pooled data set provided through six published and one unpublished cohorts. Outcomes in recipients of peripheral blood or bone marrow transplantation for hematologic malignancies were evaluated. A multivariate Cox model was used to adjust differences in outcomes of patients receiving ABO-matched grafts with those receiving major, minor, or bidirectional mismatched grafts. Considering multiple testing, p values of less than 0.05 and 0.001 were considered significant for the primary and secondary endpoints, respectively. RESULTS: In all, 1208 cases, including 697 ABO-matched and 202 major, 228 minor, and 81 bidirectional mismatched transplants, were analyzed. Overall, adverse impact of ABO matching on overall survival (OS), as a primary endpoint, was not observed (adjusted hazard ratios [95% confidence intervals]: major, 1.03 [0.82-1.30], p = 0.81; minor, 1.19 [0.97-1.47], p = 0.10; bidirectional, 1.25 [0.91-1.72], p = 0.17). Among related stem cell recipients, ABO matching had no significant influence on OS, while the minor and bidirectional mismatched groups among unrelated stem cell recipients exhibited lower OS with marginal significance, especially in patients with acute leukemia, patients who received transplants after 1998, and patients who underwent transplants at Asian centers. CONCLUSIONS: Our meta-analysis demonstrates no adverse association between any ABO mismatching and survival. However, marginally lower OS found in recipients of minor or bidirectional mismatched grafts from unrelated donors suggested the need for larger studies focusing on unrelated transplants.

Cis-AB, the Blood Group of Many Faces, Is a Conundrum to the Novice Eye.

Cis-AB, a rare ABO variant, is caused by a gene mutation that results in a single glycosyltransferase enzyme with dual A and B glycosyltransferase activities. It is the most frequent ABO subgroup in Korea, and it occurs more frequently in the East Asian region than in the rest of the world. The typical phenotype of cis-AB is A2B3, but it can express various phenotypes when paired with an A or B allele, which can lead to misclassification in the ABO grouping and consequently to adverse hemolytic transfusion reactions. While cis-AB was first discovered as having an unusual inheritance pattern, it was later found that both A and B antigens are expressed from the same allele inherited from a single parent; hence, the name cis-AB. Earlier studies relied on serological and familial investigation of cis-AB subjects, but its detection has become much easier with the introduction of molecular methods. This review will summarize the serological variety, genetic basis and inheritance pattern, laboratory methods of investigation, clinical significance, and the blood type of choice for transfusion for the cis-AB blood group.

Safety issues related to the electronic cross-matching of blood in mainland China: A prospective cohort study involving cross-matching of 40,228 blood samples.

Although the electronic cross-matching of blood has been widely applied in some developed countries and regions, concern over the risk of undetected red blood cell (RBC) antibodies has limited its application in mainland China.This study was performed to explore the missed detection rate of RBC antibodies in a Chinese population from 2011 to 2016. If the results of 2 consecutive tests of ABO/RhD blood group identification were consistent and antibody screening results were negative, electronic cross-matching of the blood was performed. In addition, traditional serological cross-matching of blood (polybrene method) and a parallel experiment for electronic cross-matching of blood were performed to analyze the missed detection of unexpected RBC antibodies in blood donors and recipients.Using the polybrene method, 40,228 blood samples were tested by parallel traditional serological cross-matching of blood; among these samples, blood compatibility was found in 40,222 cases, primary incompatibility (incompatibility of the donor's erythrocytes with the recipient's serum) was found in 6 cases, and no secondary incompatibility was found. Identification of antibody specificity was performed using panel cells, and all unexpected RBC antibodies were confirmed as anti-Mur alloantibodies in the MNS system.Further improvements in the erythrocyte antigenic spectrum, especially the Mur antigen in Asian populations, are expected to ensure the safety of implementing electronic cross-matching in China.

Effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats.

BACKGROUND: Novel feline RBC antigens might contribute to decreased efficacy of RBC transfusion and increased incidence of acute transfusion reactions (ATR). OBJECTIVES: To examine the effect of major cross-match in transfusion-naïve anemic cats on the incidence of acute immunologic transfusion reaction and transfusion efficacy for up to 24 hours after transfusion. ANIMALS: Forty-eight client owned transfusion-naïve anemic cats. METHODS: Prospective, randomized, controlled study. All transfusion-naïve cats receiving packed red blood cells (pRBC) transfusions from January 2016 to August 2017 were eligible for inclusion. Cats in the study group received cross-match and blood type compatible pRBCs and cats in the control group received noncross-matched blood type compatible pRBCs. Incidence of ATR and change in PCV after transfusion was recorded. RESULTS: No significant difference in incidence of transfusion reactions between cross-matched and noncross-matched groups (CM+ 4/24; 17%, CM- 7/24; 29%, P = .16). No significant difference between groups in mean change in PCV after transfusion scaled to dose of pRBCs administered at any time point after transfusion (immediate: CM+ 0.62 ± 0.59, CM- 0.75 ± 0.48, P = .41; 1 hour: CM+ 0.60 ± 0.66, CM- 0.74 ± 0.53, P = .43; 12 hours: CM+ 0.70 ± 0.55, CM- 0.66 ± 0.60, P = .81; 24 hours: CM+ 0.64 ± 0.71, CM- 0.55 ± 0.48, P = .70). CONCLUSIONS AND CLINICAL IMPORTANCE: Our results do not support use of the major cross-match test to increase efficacy of, and to decrease adverse events associated with, RBC transfusion in AB blood typed transfusion-naïve cats.

Red blood cell transfusions in cats: 126 cases (1999).

OBJECTIVE: To determine the number of and reasons for RBC transfusions, incidence of acute transfusion reactions, prevalence of blood types, volume of blood administered, change in PCV, and clinical outcome in cats. DESIGN: Retrospective study. ANIMALS: 126 cats that received RBC transfusions. PROCEDURE: Medical records of cats that received whole blood or packed RBC transfusions were reviewed for signalment, blood type, pre- and post-transfusion PCV, volume of blood product administered, clinical diagnosis and cause of anemia, clinical signs of acute transfusion reactions, and clinical outcome. RESULTS: Mean volume of whole blood administered i.v. was 172 mL/kg (7.8 mL/lb) versus 9.3 mL/kg (4.2 mL/lb) for packed RBCs. Ninety-four percent of cats had blood type A. Mean increase in PCV among all cats was 6%. Fifty-two percent of cats had anemia attributed to blood loss, 10% had anemia attributed to hemolysis, and 38% had anemia attributed to erythropoietic failure. Acute transfusion reactions occurred in 11 cats. Sixty percent of cats survived until discharge. CONCLUSIONS AND CLINICAL RELEVANCE: RBC transfusions resulted in an increase in PCV in cats with all causes of anemia in this study. The rate of death was greater than in cats that did not receive transfusions, but seriousness of the underlying disease in the 2 groups may not be comparable. Death rate of cats that received transfusions was not attributable to a high rate of transfusion reactions. Results confirm that pretransfusion blood typing or crossmatching is required to minimize the risk of adverse reactions.

One antigen mismatched related donor bone marrow transplant in a patient with acute lymphoblastic leukaemia and beta-thalassaemia major: potential cure of both marrow disorders.

We report a case of a 34-year-old man with T-ALL and beta-thalassaemia major who underwent a one antigen mismatched related donor bone marrow transplant. Five months post transplant chimeric studies revealed full donor haemopoiesis and the patient remains leukaemia and thalassaemia free at 12 months post transplant. Cumulative risk factors contributing to the increased transplant-related mortality in patients with two different marrow disorders are discussed.

Delayed haemolytic transfusion reaction due to anti-Jkb in a patient with non-Hodgkin's lymphoma-transient nature of anti-Jkb and the importance of early serological diagnosis.

Delayed haemolytic transfusion reactions (DHTRs) are relatively common following blood transfusions. In the UK, DHTRs were responsible for 10.2% of all serious transfusion-related hazards between 1996 and 2003. In most cases, there is minor or no morbidity, and the reaction may go unnoticed. However, in some cases, a large fall in haemoglobin level and major morbidity may occur. Even in such serious cases, the true cause of the patient's clinical deterioration may be unrecognized if serological investigation is not carried out immediately because of the often transient nature of the antibodies involved. Failure to make the correct diagnosis will lead to inappropriate treatment and expose the patient to risk of further serious transfusion reactions. We describe a case of DHTR caused by anti-Jk(b) antibodies, which illustrates the difficulty in diagnosing this common but under-recognized reaction and shows the transient nature of the antibody involved, which became undetectable within 4 weeks.

Implications for urgent transfusion of uncrossmatched blood in the emergency department: The prevalence of clinically significant red cell antibodies within different patient groups.

OBJECTIVE: To define the prevalence of alloantibodies as a factor of age and underlying clinical disease, with particular relevance to the prediction of the safety of uncrossmatched blood in different demographic groups. METHODS: A retrospective review was conducted of all immunohaematological studies on blood samples submitted to the blood bank of a tertiary referral hospital between January 1998 and December 1999. RESULTS: A total of 27 968 antibody screens in 15 966 patients were analysed. When only clinically significant antibodies were considered, the total alloimmunization prevalence was 1.9% and the prevalence of antibodies capable of causing an immediate transfusion reaction was 0.6%. The prevalence of antibodies capable of causing an immediate transfusion reaction was 0.1% in the under 30 years of age group. Clinically significant antibodies were found in 5.1% in the haematology and oncology unit patients. The risk rises with age and female sex. CONCLUSION: We conclude that uncrossmatched blood is associated with low risk in patients < 30 years of age. The knowledge that patients have not been exposed to previous transfusion or pregnancy will reduce the risk even further.