ABO Matching Research Articles

Donor-specific anti-HLA antibodies (DSAs) in patients undergoing allogeneic hematopoietic stem cell transplantation from mismatched donors on behalf of GITMO and AIBT.

Antibodies directed against donor-specific HLA allele(s)/antigen(s) (DSAs) represent a known risk factor for hematopoietic stem cell transplantation (HSCT) engraftment. Still, the overall management needs to be standardized. GITMO and AIBT ran a survey on DSAs in Italian Transplant Programs including mismatched HSCT performed between January 2014 and June 2017. One-thousand-thirty-three patients were proposed for the study, 804 were evaluable. Overall, 355 (44%) were screened: 91/355 (25.6%) showed anti-HLA antibodies, 23 DSAs (6.5%). Female gender and at least 4 previous pregnancies showed an impact on alloimmunization. Eleven patients with DSAs underwent desensitization. In seven cases no desensitization was employed. An alternative donor was selected for five patients. Neutrophil and platelet engraftment were obtained in 93.6% and 86.6% of the whole population, respectively, and were statistically associated with the absence of anti-HLA antibodies, ABO match, a higher number of infused nucleated cells and lack of a-GvHD. In addition, significant factors for platelet engraftment were the use of leuco-depleted transfusions, HLA match, younger age of the patient. Graft failure (GF) was associated with bone marrow stem cell source, and a lower number of infused CD34+. The detection of antibodies directed against both HLA classes, donor and patient age, the hematologic and molecular remission at HSCT, HLA match, ANC and PLTS engraftment, full donor engraftment within 28 days after HSCT, early and late GF, grade>II a-GVHD showed an impact on OS. Anti-HLA antibodies and DSAs were confirmed as risk factors affecting OS. DSAs were managed with various approaches resulting in stable engraftment in 81.9% of patients. Our study supports the clinical relevance of DSAs detection and management in mmHSCT. A standardized approach of DS is warranted.

Application of lacrimal gland ultrasonography in the evaluation of chronic ocular graft-versus-host-disease.

To investigate the effectiveness of lacrimal gland ultrasonography in the assessment of chronic ocular graft-versus-host-disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to establish the correlation between the ocular surface and ultrasonographic results. The cross-sectional study included 57 participants aged 18 and older, who were at least 100 days after allo-HSCT. The study was conducted at the oGVHD clinic of Peking University People's Hospital between March to June 2023. Patients were categorized into groups according to the International Chronic oGVHD (ICCGVHD) consensus group diagnostic criteria or the 2005 National Institutes of Health (NIH) classification criteria for Chronic GVHD. Demographics and transplantation-related information were collected for all participants, including age, gender, donor-recipient HLA matching, donor-recipient ABO matching, donor-recipient gender combination and duration after allo-HSCT. The disease activity of oGVHD and the severity of ocular surface involvement were assessed using various parameters such as Ocular Surface Disease Index (OSDI), Schirmer test, tear film break-up time (BUT), tear meniscus height, corneal/conjunctival staining and meibomian gland dropout. Lacrimal gland structures were assessed by B-mode and Doppler ultrasonography to measure parameters such as the long diameter, thick diameter, homogeneity and parenchymal vascularization. Statistical analyses were performed to determine differences in ocular surface conditions and lacrimal gland ultrasonographic parameters between groups as well as to determine the correlation between ocular surface condition and lacrimal gland ultrasonographic findings. (1) Patients with definite and probable oGVHD exhibited a significantly longer duration after allo-HSCT compared to non-oGVHD patients (H=11.264, p<0.01), The median durations were 247(164,894) days and 525(310,928) days, respectively, compared to 204(169,323.25) days for non-oGVHD patients. (2) Compared to non-oGVHD patients, both definite oGVHD patients and probable oGVHD patients showed lower average of Schirmer test (H=31.188, p<0.01), TBUT (H=11.853, p<0.01), tear meniscus height (H=13.630, p<0.01) and higher average of OSDI (F=27.992, p<0.01), corneal staining scores (χ²=23.66, p<0.05) and temporal conjunctival staining scores (χ²=14.84, p<0.05). (3) The B-mode and Doppler ultrasonography parameters in lacrimal glands including long diameter, thick diameter, homogeneity and parenchymal vascularization did not exhibit significant differences between the three groups. (4) The long diameter in lacrimal ultrasonography had significantly positive correlations with tear meniscus height (r=0.297, p<0.05) and significantly negative correlations with temporal conjunctival staining scores (r=-0.313, p<0.05) and staining total scores (r=-0.285, p<0.05). The thick diameter in lacrimal ultrasonography demonstrated significantly positive correlations with tear meniscus height (r=0.404, p<0.01), and significantly negative correlations with OSDI (r=-0.273, p<0.05), corneal staining scores (r=-0.264, p<0.05), nasal conjunctival staining scores (r=-0.271, p<0.05) and staining total scores (r=-0.312, p<0.05). Homogeneity and parenchymal vascularization were not found to be significantly correlated with ocular surface status. The ocular surface condition in oGVHD patients is worse than that observed in non-GVHD patients. The main manifestations include keratoconjunctival injury and a reduction in tear secretion and tear film stability. These effects appear to be a common result of chemoradiotherapy-induced inflammation and rejection-associated responses. There were no significant differences in the morphology of lacrimal glands as revealed by ultrasonography. This suggests that ocular rejection may not be the primary cause of lacrimal gland changes in oGVHD patients. While ultrasonography can provide insight into tear secretion, its efficacy in diagnosing oGVHD appears limited.

Factors affecting the efficacy of human leukocyte antigen-selected platelet provision: A large retrospective study in the United Kingdom.

A large, retrospective study was designed to interrogate current NHS Blood and Transplant (NHSBT) HLA matching strategies for the provision of HLA selected platelets (HLA SP) and to determine whether additional factors such as ABO blood group matching, patient diagnosis, patient and/or donor age, sex, ethnicity, age of platelet unit at transfusion and possibly seasonal variation also play a role in transfusion efficacy. Data for 56 640 HLA SP transfusions over a 3-year period were collected. Transfusions with missing data for any factor under consideration were excluded, resulting in a cohort of 13 044 transfusions for analysis. Univariable and multivariable regression models were used to determine if any factors influenced an increase in platelet count of ≥10 × 109/L. A stepwise logistic regression was applied, such that each influential factor was adjusted for effects on other factors included in the study. HLA match grade was confirmed as a significant factor in transfusion efficacy, with ABO mismatched units 20% less likely to give an adequate platelet increment (≥10 × 109/L). Platelet donor age, gender and ethnicity were not significant. Conversely, patient diagnosis, ethnicity, gender and age showed significant associations with platelet increments. Some seasonal variation in efficacy of platelet transfusion was also demonstrated. This study has demonstrated the efficacy of HLA SP transfusions in refractory patients with a wide range of diagnoses, the importance of HLA match grade, plus the marginal effect of ABO matching. A wide range of donor-related factors was excluded, while a number of patient-related factors were identified, requiring more extensive investigation in ongoing and independent studies, with implications for donor registry, clinical and laboratory practices.

Going the distance: Geographic effects of the lung transplant composite allocation score

Going the distance: Geographic effects of the lung transplant composite allocation score

Favorable outcome of non-myeloablative allogeneic transplantation in adult patients with severe sickle cell disease: A single center experience of 200 patients.

Allogeneic hematopoietic stem cell transplant (HSCT) for adults with severe sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors predicting event free survival (EFS). Adults with severe SCD undergoing NMA match-related donor allogeneic HSCT from 2015 to 2021 with at least 12 months of follow-up were included. A total of 200 patients were included with a median age of 26 years (14-43) and 56% were male. The median infused CD34 dose was 13.7 (5.07-25.8), respectively. Median absolute neutrophil count engraftment was 19 (13-39) days with 51% of patients receiving GCSF to expedite recovery. A total of 17 patients experienced GF; 3 as primary and 14 as secondary within a median time of 204 days (40-905). A 76% successfully discontinued sirolimus at the last follow-up. Median follow-up for the cohort is 29.2 (2.1-71.4) months. Estimated 3-year EFS and OS were 88.2% (81.9-92.5) and 94.6% (89.2-97.3). At multivariable analysis, minor ABC incompatibility hazard ratio (HR) 4 (1.3-12.1; 0.014) and allo-antibody against non-ABO donor antigens HR 4.3 (1.3-14.1; 0.016) were significant for EFS. No clonal evolution or myeloid malignancies were seen. This largest single-center report of NMA HSCT in adults with severe SCD further delineated its feasibility, potential toxicities, and fertility outcomes. GF remains a major impediment and appears dependent on ABO matching and non-ABO antibodies.

Extended RBC Phenotype Matching Reduces the Incidence of Alloimmunization in Patients with Warm Autoimmune Haemolytic Anaemia (wAIHA)

Background: Warm Autoimmune Haemolytic Anaemia (wAIHA) involves autoantibodies destroying red blood cells, often necessitating transfusions. Alloimmunization, the formation of antibodies against non-self-Red Blood Cells (RBC) antigens, complicates future transfusions. This review evaluates whether extended RBC phenotype matching reduces alloimmunization compared to standard ABO and Rh matching. Methods: Databases (PubMed, Scopus, Cochrane Library and Google Scholar) were searched for studies (2014- 2024) on wAIHA patients comparing basic, partial and full extended RBC phenotype matching. Eligible data were analysed using a random-effects model to assess alloimmunization risk reduction. Manual searches were performed using relevant references. Results: Ten studies, both retrospective and prospective, were included. Basic matching (ABO and Rh) had the highest alloimmunization rate at 32.8% (95% CI: 13.3%-52.2%; I2=95.79%, p&lt;0.001). Partial matching (Rh and Kell) reduced rates to 22.5% (95% CI: 10.4%-34.6%; I2=49.57%, p=0.046), while full matching lowered it to 11.6% (95% CI: 4.5%18.7%; I2=73.65%, p=0.001). Despite heterogeneity, results consistently showed extended matching reduced alloimmunization. Conclusion: Extended RBC phenotype matching significantly lowers alloimmunization risk in wAIHA patients, particularly in chronically transfused cases. However, the variability across studies highlights the need for standardised transfusion practices and further research to confirm these results through larger, randomised controlled trials. Keywords Alloimmunization; RBC phenotype matching; Transfusion; Anaemia; Antibody formation

Clinical and Immunological Factors Associated with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis Patients

Clinical and Immunological Factors Associated with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis Patients

ABO and RhD matching in platelet transfusions: Real‑world data

matching in platelet transfusions varies widely worldwide, since it does not preclude good clinical responses. However, it has been shown that ABO and RhD matching selection for platelet transfusions raises efficacy and safety concerns. The present study aimed to assess and evaluate ABO and RhD matching in platelet transfusions. The present study was part of a national survey that evaluated the platelet units, and ABO and RhD blood group of patients, along with the number of platelet units produced and transfused from May to June, 2015. A total of 13,250 [12,061 random donor platelets (RDPs) and 1,189 single donor platelets (SDPs)] were evaluated. ABO identical platelets were transfused in 58.99±0.88% RDPs and 45.75±2.87% SDPs. ABO major incompatible platelets (with antigen incompatibility) were transfused in 15.92±0.66% RDPs and 24.05±2.47% SDPs. ABO minor incompatible platelets (with plasma incompatibility) were transfused in 19.70±0.71% and 22.96±2.43% RDPs and SDPs, respectively, while a combination of ABO major and minor incompatible platelets (combination of plasma and antigen incompatibility) in 5.38±0.41% and 7.23±1.51%, RDPs and SDPs respectively. A total of 6.69 and 12.29% of RhD-positive RDPs and SDPs were transfused in RhD-negative patients (both P<0.001). On the whole, the analysis of real-world data indicates variations in platelet ABO and RhD matching. Further studies are required to elucidate the real impact in the management of patients, while the upcoming centralization of blood services may also be a decisive step in this direction.

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan.

Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact ofABO compatibility and incompatibility onoutcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positivedirect Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.

Herombopag for Enhancement of Platelet Engraftment in Patients Undergoing Hematopoietic Stem Cell Transplantation

Herombopag for Enhancement of Platelet Engraftment in Patients Undergoing Hematopoietic Stem Cell Transplantation

Is ABO Compatibility Important in Islet Transplantation?

One of the current criteria for clinical islet allotransplantation is ABO blood group compatibility between donor and recipient.1 The distribution of ABH antigens in human pancreata was first examined >40 y ago, revealing expression in acinar and vascular cells but not in islets.2 This underlined the importance of ABO matching in whole pancreas transplantation, but the situation in islet transplantation is more complicated. Although islets in situ appear to be ABH-negative,2 islets prepared for transplant are invariably contaminated with exocrine tissue including acinar cells. Furthermore, it is not known whether the islet isolation and transplantation process itself influence ABH expression. It is therefore somewhat surprising that ABH expression in islet preparations before and after transplant has not been characterized until now. In this issue of Transplantation, Verhoeff et al3 present a detailed immunohistochemical and flow cytometric survey of ABH antigen levels in human pancreatic tissue, isolated human clinical-grade islets, and islets derived from human embryonic stem cells (hESCs). After confirming that ABH antigens are present on acinar cells but not on endocrine and ductal cells in the pancreas, the authors demonstrate that islet preparations consist primarily of ABH-negative endocrine cells but are significantly contaminated with ABH-positive acinar cells. When islets were transplanted into immunodeficient rats, the endocrine component was ABH-negative at 24 wk, whereas remnant acinar tissue stained positive. Pancreatic endocrine progenitors derived from hESCs were ABH-negative and remained so after in vivo maturation following transplantation into rats, although this was not unexpected given that the hESC donor was blood group O. The human-to-immunodeficient rat islet xenograft model used in the latter part of the study does have some limitations. First, the kidney subcapsular site does not accurately reflect the clinical scenario, in which islets are transplanted intraportally.1 Subcapsular delivery co-localizes the islets with acinar tissue fragments and potentially exposes the islets to “bystander” injury and inflammation when anti-ABH antibodies attack the acinar cells. In contrast, intraportal delivery disperses islets and acinar fragments widely throughout the liver microvasculature, which probably minimizes co-localization and thus reduces the likelihood of bystander effects. Furthermore, subcapsular but not intraportal delivery shields the graft from exposure to anti-ABH IgM antibodies. Although these differences are not relevant in the immunodeficient rat model, they may well be relevant in the clinical setting. Second, the immunodeficient rat model does not allow investigation of the importance of the in vivo anti-ABH immune response to islet grafts. I have worked with one of the authors (L.J.W.) to develop a mouse model of anti-A antibody-mediated rejection of transgenic blood group A-expressing cardiac grafts.4 However, these A-transgenic donor mice are unsuitable for examining anti-A–mediated islet graft rejection because expression of the antigen is endothelial cell-restricted and absent on islets. Humanized mouse models may be more appropriate, as suggested by the authors. The take-home message of this interesting paper is that ABO matching is indeed likely to be important in islet allotransplantation—as is the case for HLA matching5—but may become less so if islet purification efficiency improves sufficiently or if hESC-derived islets are used. On the former point, the authors speculate that the restriction of surface expression of ABH antigens to acinar tissue (starkly illustrated by Figure 6A in the paper) provides an opportunity to enrich the purity of A, B, or AB islets by some form of negative selection. Although practicality at scale may be an issue, this is an intriguing proposition that is worthy of further consideration.

Red blood cell alloimmunization among recipients of blood transfusion in India: A systematic review and meta-analysis.

There is a varied prevalence of red cell alloimmunization being reported from different parts of India. This study aimed to estimate the overall prevalence of alloimmunization in India by performing a systematic review of the literature and to establish the most suitable antigen-matching strategy to reduce the red blood cell (RBC) alloimmunization rate among transfusion recipients. A systematic search of all the original articles published in English on RBC alloimmunization among transfusion recipients from India in MEDLINE, SCOPUS, CINAHL and Google Scholar bibliographic databases was conducted. After screening the articles as per inclusion/exclusion criteria, data extraction was done independently by two sets of investigators. Meta-analysis was performed by the binary random-effects model using the restricted maximum likelihood method. A total of 44 studies on RBC alloimmunization, with a cumulative sample size of 309,986 patients, were grouped into hospital-based and multiply-transfused patients, which yielded a prevalence of 0.5 (95% confidence interval; 0.3-0.8) and 4.8 (95% confidence interval; 3.9-5.7) per 100 patients, respectively. As many as 1992 alloantibodies were identified among the 1846 alloimmunized patients. The most common antibody identified was anti-E (127; 31.99%), followed by anti-c (75; 18.89%) in multiply-transfused patients. The rate of alloimmunization was 0.5 per 100 patients tested for antibodies and 4.8 per 100 patients receiving transfusion. Considering E- and c-antigen-matched red cells along with ABO and RhD matching may significantly reduce the overall occurrence of alloimmunization among Indian population who are transfusion-dependent.

Impact of Donor-to-Recipient ABO Mismatch on Outcomes of Antithymocyte Globulin-Based Peripheral Blood Stem Cell-Derived Myeloablative Conditioning Haploidentical Stem Cell Transplantation

Impact of Donor-to-Recipient ABO Mismatch on Outcomes of Antithymocyte Globulin-Based Peripheral Blood Stem Cell-Derived Myeloablative Conditioning Haploidentical Stem Cell Transplantation

Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs.

Donor organ allocation is dependent on ABO matching, restricting the opportunity for some patients to receive a life-saving transplant. The enzymes FpGalNAc deacetylase and FpGalactosaminidase, used in combination, have been described to effectively convert group A (ABO-A) red blood cells (RBCs) to group O (ABO-O). Here, we study the safety and preclinical efficacy of using these enzymes to remove A antigen (A-Ag) from human donor lungs using ex vivo lung perfusion (EVLP). First, the ability of these enzymes to remove A-Ag in organ perfusate solutions was examined on five human ABO-A1 RBC samples and three human aortae after static incubation. The enzymes removed greater than 99 and 90% A-Ag from RBCs and aortae, respectively, at concentrations as low as 1 μg/ml. Eight ABO-A1 human lungs were then treated by EVLP. Baseline analyses of A-Ag in lungs revealed expression predominantly in the endothelial and epithelial cells. EVLP of lungs with enzyme-containing perfusate removed over 97% of endothelial A-Ag within 4 hours. No treatment-related acute lung toxicity was observed. An ABO-incompatible transplant was then simulated with an ex vivo model of antibody-mediated rejection using ABO-O plasma as the surrogate for the recipient circulation using three donor lungs. The treatment of donor lungs minimized antibody binding, complement deposition, and antibody-mediated injury as compared with control lungs. These results show that depletion of donor lung A-Ag can be achieved with EVLP treatment. This strategy has the potential to expand ABO-incompatible lung transplantation and lead to improvements in fairness of organ allocation.

The Effect of Immunized Platelet Transfusion Refractoriness on Allo-HSCT Patients with Malignant Hematological Diseases

The Effect of Immunized Platelet Transfusion Refractoriness on Allo-HSCT Patients with Malignant Hematological Diseases

ABO Mismatch in Allogeneic Hematopoietic Stem Cell Transplant: Effect on Short- and Long-term Outcomes.

The impact of ABO incompatibility (ABO-I) on hematopoietic stem cell transplant outcomes is still debated. We retrospectively investigated 432 consecutive transplants performed at our center (2012-2020). All patients but 6 were affected by hematologic malignancies. The effect of different ABO match combinations on engraftment rate, transfusion support, acute and chronic graft-versus-host disease incidences, nonrelapse mortality (NRM), disease-free survival, and overall survival was assessed in univariate and multivariate analysis. Significance was set at P < 0.05. ABO match distribution among transplants was as follows: 223 ABO-compatible, 94 major ABO-I, 82 minor ABO-I, and 33 bidirectional ABO-I. At univariate analysis, major ABO-I delayed the engraftment of neutrophils, platelets, and erythroid cells. At multivariate analysis, major ABO-I transplants displayed delayed erythroid engraftment (odds ratio [OR], 0.51; 95% confidence intervals [CIs], 0.38-0.70; P < 0.0001) and hindered transfusion independence for both red blood cells (OR, 0.52; 95% CI, 0.37-0.72; P = 0.0001) and platelets (0.60; 95% CI, 0.45-0.86; P = 0.0048). Moreover, major ABO-I transplants received greater amounts of blood products (P < 0.0001 for red blood cells and P = 0.0447 for platelets). In comparison with other ABO matches, major ABO-I was associated with an increased NRM (OR, 1.67; 95% CI, 1.01-2.75; P = 0.0427). No effects of ABO-mismatch were found on graft-versus-host disease, disease-free survival, and overall survival. Major ABO mismatch delays multilineage engraftment hinders transfusion independence and increases NRM. The prognostic impact of transfusion burden in hematopoietic stem cell transplantation deserves to be explored.

Post-Transfusion Overall Survival for HLA- Alloimmunized Platelet Refractorythrombocytopenic Leukemia Patients

Post-Transfusion Overall Survival for HLA- Alloimmunized Platelet Refractorythrombocytopenic Leukemia Patients

Graft Failure Post Allogeneic Stem Cell Transplant: Conditioning Regimen Improves Engraftment and Survival

Graft Failure Post Allogeneic Stem Cell Transplant: Conditioning Regimen Improves Engraftment and Survival

Risk Factors and Outcomes According to Age at Transplant with an HLA Identical Sibling for Sickle Cell Disease

Risk Factors and Outcomes According to Age at Transplant with an HLA Identical Sibling for Sickle Cell Disease

High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group

Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with systemic inflammation and endothelial dysfunction, increasing risk for thromboembolic events (TEE). In 145 adult recipients who developed cGVHD after a matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 32(22%) developed at least 1 TEE event, and 14(10%) developed 2 TEE events. The 5-year cumulative incidence of TEE was 22% (95% CI, 15–29%) with a median time from cGVHD to TEE of 234 days (range, 12–2050). Median time to the development of LE DVT or PE was 107 (range, 12–1925) compared to 450 days (range, 158–1300) for UE DVT. Cumulative incidence of TEE was 9% (95% CI, 0–20%), 17% (95% CI, 9–25%), and 38% (95% CI, 22–55%) in those with mild, moderate, and severe GVHD, respectively. Higher risk for TEE was associated with cGVHD severity (hazard ratio [HR] 4.9, [95% CI, 1.1–22.0]; p = 0.03), non-O-donor to recipient ABO match compared to O-donor to O-recipient match (HR 2.7, [95% CI, 1.0–7.5]; p = 0.053), and personal history of coronary artery disease (HR 2.4, [95% CI, 1.1–5.3]; p = 0.03). TEE was not associated with 2-year non-relapse mortality or 5-year overall survival.