Impact Of ABO Incompatibility Research Articles

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.

Impact of ABO incompatibility and early antibody-mediated rejection on chronic antibody-mediated rejection in kidney transplant patients.

Early antibody-mediated rejection has been reported to increase chronic antibody-mediated rejection and decrease graft survival in kidney transplantation. However, the impact of early antibody-mediated rejection in ABO-incompatible kidney transplantation remains unclear. We retrospectively analyzed living-donor kidney transplantation patients from two Korean centers. Patients were categorized based on ABO compatibility and early antibody-mediated rejection within 1 year. The primary outcome was chronic antibody-mediated rejection. The secondary outcomes were production of de novo donor-specific antibody and composite kidney outcome, defined as graft loss or a decline in estimated glomerular filtration rate to below 30mL/min/1.73 m2. A total of 1639 patients were analyzed, including 1292 patients who underwent ABO-compatible kidney transplantation and 347 patients who underwent ABO-incompatible kidney transplantation. ABO-incompatible kidney transplantation had a lower risk of de novo donor-specific antibody production (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95) and chronic antibody-mediated rejection (HR 0.33, 95% CI 0.12-0.92) with a comparable risk of the composite kidney outcome (HR 1.06, 95% CI 0.71-1.59) compared to ABO-compatible kidney transplantation. When outcomes of ABO-incompatible kidney transplantation were analyzed according to early antibody-mediated rejection, ABO-incompatible kidney transplantation without antibody-mediated rejection had a lower risk of de novo donor-specific antibody production (HR 0.60, 95% CI 0.41-0.88) and chronic antibody-mediated rejection (HR 0.28, 95% CI 0.09-0.91) than ABO-compatible kidney transplantation without antibody-mediated rejection. However, ABO-incompatible kidney transplantation with antibody-mediated rejection showed a higher risk of de novo donor-specific antibody production and similar risk of chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation without antibody-mediated rejection. ABO-incompatible kidney transplantation showed a lower risk of de novo donor-specific antibody production and chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation; however, early antibody-mediated rejection abrogated these beneficial effects of ABO-incompatible kidney transplantation.

Recipient-Specific Antibodies (RSA) in Mismatched Related Transplants May Induce Transplant-Associated Thrombotic Microangiopathy (TA-TMA)

HLA incompatibility increases the risk of transplant-related complications. Specifically, donor-specific antibodies (DSA) in mismatched related transplants (mm-HCT) increase the risk of graft failure. Less is known about the role of recipient-specific antibodies (RSA) detected in donors, as the immune status of the donor is not routinely examined before transplant with regard to anti-HLA antibodies. These antibodies may be transferred together with transplanted cells or produced by memory donor cells. We hypothesize that donor-derived RSA may induce immune-mediated complement activation in the classical pathway (CH50), leading to overproduction of membrane attack complex (MAC) and exacerbation of endothelial damage. Here we present preliminary epidemiological data regarding the presence of DSA and RSA, and the impact of RSA antibodies on transplant-related complications, especially transplant-associated thrombotic microangiopathy (TA-TMA) and acute graft-versus-host disease (aGvHD). Methods We prospectively analyzed the presence of anti-HLA antibodies in 20 pairs of donors and recipients qualified for mm-HCT. All recipients suffered from hematological malignancies and received a myeloablative conditioning regimen and immunosuppression consisting of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients’ and donors’ immunization status were tested with the solid phase method. Tests were carried out using a flow fluorometer across the screening range (Luminex Screen, One Lambda, USA). In the group of positive samples for anti-HLA class I and/or II antibodies, identification of the specificity of the HLA antibodies was performed (Luminex Single Antigen Beads, One Lambda, USA). Reagents enabling the determination of anti-HLA antibodies in the IgG class were used. All results were presented as mean fluorescence intensity (MFI) values. Monitoring of complement activation on days 30, 60, and 100 post-transplant was started after completing epidemiological data in the first 10 pairs. All patients were checked for TA-TMA and GvHD development during routine post-transplant visits. TA-TMA screening included TA-TMA triad: hypertension or kidney injury, LDH increase and decrease in number of platelets or refractoriness to transfusions, and additionally decrease in hemoglobin concentration, proteinuria, and clinical presentation with TA-TMA involved organ damage. Schistocytes as non-objective and nonrepeatable markers were excluded from diagnostic criteria. Results Anti-HLA antibodies were detected in 9/20 (45%) of recipients, and in 9/20 (45%) of the donors despite the lack of any transfusion history in donor group. Neither the presence of DSA nor RSA was affected by gender. RSAs were present more often in donors (7/9; 77%) than DSAs in recipients (2/9; 22%); p=0.052. Data summarizing MFI values and type of antibodies are presented in table 1. Laboratory diagnosis of TA-TMA met 12/20 (60%) patients, with a significant clinical presentation including severe hypertension (3) pericarditis (1), gastrointestinal (5), or neurological (6) impairment in 8/12 (66%). All patients with RSA (7/7; 100%) developed TA-TMA compared to no-RSA group (5/13; 38%) (p<0.01). TA-TMA-mediated organ damage was noticed more often in the RSA population (5/7; 71%) compared to the no-RSA group (3/13, 23%) (p<0.01); (Table 2). A trend for higher activation of CH50 and MAC in RSA compared to a no-RSA group was noted with a mean CH50 93 vs. 82 (p=0,16), and MAC 1428 vs. 1007 (p=0,24) respectively. A trend for higher maximum concentrations of tacrolimus 14 vs 10.7 (p=0.07) was observed in patients with TA-TMA. There was no impact of ABO incompatibility on TA-TMA development. During the time of observation 6 patients (30%) developed aGvHD - grades I, II, and III were diagnosed in 3, 1, and 2 patients respectively. Only 1 patient with RSA developed aGvHD. There was no correlation between RSA and GvHD occurrence (RSA 1/7, no-RSA 5/13, p=0.26) and between aGvHD and TA-TMA. CMV reactivation was documented in 13/20 (65%) patients, with no differences between the RSA and no-RSA groups (p=0.65). Conclusions RSAs occur surprisingly often in the donor population, irrespectively to the donor`s gender and the lack of transfusions history. The exact role of these antibodies is not fully understood; however, our data may suggest their impact on complement activation and TA-TMA induction. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of ABO-Incompatibility and Early Antibody-Mediated Rejection on Kidney Allograft Outcomes

Impact of ABO-Incompatibility and Early Antibody-Mediated Rejection on Kidney Allograft Outcomes

Immuno-hematological monitoring after allogeneic stem cell transplantation: a single-center, prospective study of 104 patients.

The impact of ABO incompatibility on the outcome of hematopoietic stem cell transplantation (HSCT) is still debated. We report the results of a prospective, single-center study evaluating the impact of ABO mismatch on the development of immediate and late immuno-hematological complications, and the efficacy of the protocol used at the "Sapienza" University (Rome, Italy) to manage ABO incompatibility in patients undergoing HSCT. From January 2013 to December 2016, we prospectively analyzed all patients undergoing HSCT. Graft manipulation or desensitization strategies were used according to ABO incompatibility, donor sex and donor transfusion history. Red blood cell and platelet transfusions were given based on immunohematological features. From January 2013 to December 2016, 104 consecutive patients underwent HSCT from a matched related donor (29.81%), matched unrelated donor (53.58%), cord blood (1.9%) or haploidentical donor (14.42%). Forty-nine patients (47%) were ABO-identical and 55 (53%) ABO-incompatible (23 major, 25 minor, 7 bidirectional). Donor engraftment, graft failure or other complications did not differ between ABO compatible or incompatible patients. ABO incompatibility did not show a significant impact on graft-versus-host disease, overall survival or disease-free survival. Factors associated with the need for prolonged red blood cell support were ABO incompatibility (p=0.0395), HLA disparity between donor and recipient (p=0.004) and the onset of hemorrhagic cystitis (p=0.015). In multivariate analysis HLA disparity was the only statistically significant condition (p=0.004). ABO incompatibility does not represent a barrier to allogeneic HSCT. It is, however, associated with prolonged transfusion requirements. Close immunohematological monitoring, as a shared standard procedure, allows appropriate transfusion support to be provided and limits post-HSCT immuno-hematological complications.

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.

Impact of ABO incompatibility on outcomes after haploidentical hematopoietic stem cell transplantation for severe aplastic anemia.

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.

Pediatrik Hematopoetik Kök Hücre Transplantasyonunda ABO Uygunsuzluğunun Önemi

Pediatrik Hematopoetik Kök Hücre Transplantasyonunda ABO Uygunsuzluğunun Önemi

Impact of ABO incompatibility on patients' outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT.

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II–IV acute graft-versus-host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22–4.66; P=0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft-versus-host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II–IV acute graft-versus-host disease rates (HR 2.03; 95% CI: 1.00–4.10; P=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 – 3.18; P=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation.

Effect of ABO incompatibility on T-cell flow cytometry cross-match results prior to living donor kidney transplantation.

Due to its high sensitivity, the flow cytometry cross-match (FCXM) has been described as valuable tool for identifying an optimal donor. We here focused on the impact of ABO incompatibility on FCXM results. We analyzed 29 ABO incompatible and 89 ABO compatible donor-recipient pairs (73 and 175 datasets, respectively) prior to living donor kidney transplantation. In all patients, lymphocytotoxic cross-matches for B and T cells were negative. Recipients with blood group O (A to O and B to O) displayed significantly (P < 0.05) higher T-FCXM results than those with blood group A and B (A to B, B to A and AB to A), respectively. Donor-specific T-FCXM responses (ΔMFI values) were significantly higher (P < 0.05) in ABO incompatible vs. compatible pairs (ABO incompatible recipients with blood group O: 32 ± 6; with blood group A: 19 ± 7; with blood group B: 7 ± 4; recipients with ABO compatibility: 3 ± 2, respectively, data represent mean ± SEM). Consistent with the T-FCXM results donor-specific isohemagglutinins (IgG titers) were significantly higher in recipients with blood group O vs. A, both prior to rituximab treatment and plasmapheresis/immune adsorption (P = 0.004) and immediately prior to transplantation, i.e., after rituximab and antibody-depleting therapies (P = 0.04). ABO incompatibility was associated with higher T-FCXM responses, especially in recipients with blood group O. This finding has major impact on the interpretation of flow cross-match results. Current cut-off values need to be reassessed in the ABO incompatible setting. © 2016 International Clinical Cytometry Society.

Impact of Graft–Recipient ABO Compatibility on Outcomes after Umbilical Cord Blood Transplant for Nonmalignant Disease

Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes after hematopoietic stem cell transplantation. Because the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically overlooked graft characteristic impacted various outcomes after UCB transplantation (UCBT) for nonmalignant disorders (NMDs). A prospectively maintained institutional blood and marrow transplant program database was queried for all patients undergoing first UCBT for NMDs. UCB and recipient ABO compatibility was considered as matched, major mismatched, minor mismatched, or bidirectional mismatched. The impact of ABO incompatibility was assessed on overall survival, graft failure, acute and chronic graft-versus-host disease (GVHD), time to neutrophil and platelet recovery, day 0 to day 100 RBC transfusion burden, and donor hematopoietic chimerism. Through December 2014, 270 patients have undergone first UCBT for various NMDs. In both univariable and multivariable analyses, ABO compatibility status did not appear to impact any outcomes assessed, although a trend toward increased grades III to IV acute GVHD was seen in recipients of major mismatched units. When considering UCBT for treatment of NMDs, ABO compatibility between the donor unit and intended recipient does not appear to be an important consideration in the UCB unit choice.

The Impact of Graft/Recipient ABO Compatibility on Outcomes after Umbilical Cord Blood Transplant for Non-Malignant Disease

Background:Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes following hematopoietic cell transplantation (HCT). As the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically-overlooked graft characteristic impacted various outcomes following UCB transplantation (UCBT) for non-malignant disorders (NMD).Patients and Methods:A prospectively maintained institutional BMT program database was queried for all patients undergoing first UCBT for NMD and their demographic, disease and transplant-related characteristics. For each transplant, UCB and recipient ABO compatibility was considered (1) matched, (2) major mismatched (recipient isoagglutinins against UCB antigen), (3) minor mismatched (UCB isoagglutinins against recipient antigen), or (4) bi-directional mismatched. In double UCBT, only the compatibility status of the dominant unit was considered.The impact of ABO incompatibility was assessed on the following outcomes using Kaplan-Meier and cumulative incidence functions: graft failure, aGvHD (grade II - IV and III - IV), cGvHD, platelet recovery, and overall survival. Cumulative red blood cell transfusion exposure per patient between HCT days 0 and +100 (c-RBC) was obtained from laboratory records. Donor hematopoietic chimerism values on the myeloid fraction of peripheral blood were reviewed at day +100 and most recent time assessed. HLA typing was at the antigen level for HLA-A and -B and allele level at -DRB1; in double UCBT, the matching status of the dominant unit was considered.Results:Through December 2014, 270 patients have undergone first UCBT for various NMD (inherited metabolic disorder = 165; marrow failure = 71; other = 34). The mean age at UCBT was 7.9 years (± 9.6). Most patients had a maximal performance score before UCBT (Lansky/Karnofsky of 100, n = 162; 60%) and were male (n = 164; 61%). Most patients received a single UCB unit (n = 225; 83%) and the majority of grafts were unrelated (n = 253; 94%). The average total nucleated cell dose was 8.0 x 107/kg (± 6). With respect to HLA-matching, 79 (29%) received matched, 133 (49%) single-mismatched and 57 (21%) two-mismatched grafts. Most patients received myeloablative conditioning (n = 209; 77%) and GvHD prophylaxis with cyclosporine and mycophenolate mofetil (n = 150; 56%). Negative CMV serostatus in both the graft and recipient was most common (n = 172; 64%).ABO compatibility for the cohort was as follows: matched, n = 93 (34%); major mismatch, n = 72 (27%); minor mismatch, n = 80 (30%); bi-directional mismatch, n = 23 (9%). ABO compatibility status was indeterminate in 2 transplants. Among all 4 ABO compatibility groups, no significant difference was seen in age, gender, NMD diagnosis category, conditioning intensity, HLA-matching, cell dose, number of UCB units, transplant era, performance score, GvHD prophylaxis, or CMV serostatus. Related UCB unit transplants were more likely to be ABO matched.Table 1 shows outcomes by ABO compatibility group with a median follow-up time of 4.5 years (range, 0.5 - 20). ABO compatibility status did not appear to impact any outcomes assessed, though a trend toward increased grade III - IV aGvHD was seen in recipients of major mismatched units.Table 1Outcomes after UCBT for NMD by ABO Compatibility StatusOutcomeABO Match (n=93)Minor Mismatch (n=80)Major Mismatch (n=72)Bidirectional Mismatch (n=23)P-valueOverall survival, 5 y estimate (95% CI)65% (53-74)72% (59-81)68% (54-78)76% (51-89)0.62aGVHD (II - IV) (95% CI)20% (12-29)25% (15-35)27% (16-38)28% (8-49)0.75aGVHD (III - IV) (95% CI)8% (2-15)8% (2-14)20% (10-29)5% (1-14)0.09cGVHD at 5 y (95% CI)8% (2-15)7% (1-13)8% (1-15)5% (1-15)0.96Graft failure (95% CI)19% (11-28)20% (11-29)25% (15-35)17% (2-34)0.83Platelet recovery at 1 y (95% CI)74% (65-83)75% (65-85)67% (55-78)70% (48-91)0.77Day 100 chimerism, ≥ 80% (95% CI)69% (58-79)70% (60-81)66% (54-78)75% (56-94)0.89Most recent chimerism, ≥ 80% (95% CI)79% (71-87)75% (65-84)66% (55-77)74% (56-92)0.33c-RBC (Day 0 to +100) median (inter-quartile range)11 (6-16)10 (6-20)10 (6-19)14 (8-21)0.75y = year; CI = confidence intervalConclusion:ABO compatibility status did not seem to impact outcomes following UCBT for our large NMD cohort. Further analysis of the cohort to exclude interference on some outcomes assessed will be needed for a more definitive conclusion. DisclosuresNo relevant conflicts of interest to declare.

Impact of ABO Incompatibility on the Development of Acute Antibody-Mediated Rejection in Kidney Transplant Recipients Presensitized to HLA

Whether the coexistence of anti-A/B antibody and donor specific anti-HLA antibody (HLA-DSA) has a synergistic impact on the development of acute antibody-mediated rejection (AAMR) in kidney transplant recipients (KTRs) is unclear. This study includes 92 KTRs who received a kidney from an ABO-incompatible (ABOi) donor or were presensitized to donor HLA (HLAs) and 292 controls (CONT). HLAs was defined as a crossmatch positivity or the presence of HLA-DSA. We compared the incidence of AAMR among ABOi (n = 58), ABOi+HLAs (n = 12), HLAs (n = 22), and CONT (n = 292) groups and evaluated the risk factors and antibody type (anti-A/B vs. HLA-DSA) responsible for AAMR. AAMR developed less frequently in ABOi and CONT than in the ABOi+HLAs or HLAs (P < 0.05 for all); however, there was no difference between the ABOi+HLAs and HLAs groups. AAMR developed more frequently with strong HLA-DSA at baseline; however, high baseline anti-A/B titer did not affect AAMR development. Strong baseline HLA-DSA was an independent predictor for AAMR, however the baseline anti-A/B titer was not. All four AAMR episodes in ABOi+HLAs were positive to HLA-DSA but not to anti-A/B. In conclusion, ABO incompatibility does not increase the risk for AAMR in HLAs KTRs.

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT.

The impact of ABO incompatibility on clinical outcomes following haematopoietic SCT (HSCT) remains controversial. This retrospective study assessed the effect of ABO mismatch on transplant outcomes and transfusion requirements in 594 patients undergoing reduced-intensity conditioned (RIC) HSCT with alemtuzumab in three UK transplant centres. We found no significant effects of minor, major or bidirectional ABO mismatch on overall survival, relapse-free survival, nonrelapse mortality or relapse incidence. Although the rate of acute GVHD was unaffected by ABO mismatch, the incidence of extensive chronic GVHD was higher in patients with minor and major mismatch compared with those who were ABO matched (hazard ratio (HR) 1.74, P=0.032 for minor, HR 1.69 P=0.0036 for major mismatch). Red cell and platelet transfusion requirements in the first 100 days post transplant did not differ by ABO mismatch. In this large UK series, ABO mismatch in RIC HSCT has no clinically significant effect on survival outcomes but appears to modify susceptibility to extensive chronic GVHD.

Impact of ABO Incompatibility on Engraftment , Transfusion Requirement and Survival after Unrelated Cord Blood Transplantation：a Single Institute Experience in China

Few reports have focused on the impact of ABO incompatibility on the clinical outcomes, after unrelated cord blood transplantation (UCBT). Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 177 patients with hematologic malignancies, which underwent single UCBT in Anhui Provincial Hospital from May 2008 to April 2014. The study patients included 86 ABO-identical, 52 minor, 32 major, and 11 bidirectional ABO-incompatible recipients. All of them received a homogeneous intensified myeloablative pre-transplantation conditioning regimen of total body irradiation (TBI)cyclophosphamide (CY) [TBI (total,12 Gy; four fractions) and CY (60 mg/kg daily for 2 days)] (age≥14 years) or BuCY2 [busulfan (0.8 mg/kg every 6 h for 4 days) and CY]. Medians of 3.85×107/kg (range, 1.03-10.43) total nucleated cell (TNC) and 2.0×105/kg (range, 0.45-6.88) CD34+cells were transfused.Of the 177 patients who underwent UCBT, 169 achieved successful neutrophil engraftment. In patients receiving ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the cumulative incidences of neutrophil engraftment were 92.7%, 100%, 96.9% and 90.9%, respectively (P=0.509). The median days to achieve neutrophil engraftment were 17, 18, 17, and 20, respectively (P=0.409). The cumulative incidences of platelet engraftment were 81.7%, 86.5% , 87.5% and 63.6%, respectively(P=0.436) .And the median days to achieve platelet engraftment for the 4 groups were 36, 40, 36, and 38, respectively; (P=0.545). All of the data did not show any significant difference among the 4 groups. Neutrophil engraftment(cumulative incidence, 95.5% versus 95.3% , P=0.861; median day, 17 versus 18, P=0.717) also did not differ significantly between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients (HR1.08, P=0.680). And platelet engraftment (83.6% versus 81.4%, P=0.964; median day, 38 versus 37, P=0.699) reached the similar result (HR1.104, P=0.621).We investigated the results from a 169-patient population with neutrophil engraftment, the average units of platelets (Plts) and red blood cells (RBCs) transfused during the hospitalization after the UCBT were 0.204 units/kg(range, 0.03-1.45)and 0.159 units/kg (range, 0-1.56).In patients with ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the average units of Plts transfused after UCBT were 0.221, 0.202, 0.169, and 0.195 units/kg(P=0.53), respectively, and the average units of RBCs transfused were 0.151, 0.156, 0.163, and 0.221 units/kg (P=0.847), respectively. No significant differences in the transfusion requirements among the 4 groups were noted, so did the comparison between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients.With a median follow-up of 12 months (range, 3-74 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 67.1%, 57.7%, 62.5 % and 54.5%, respectively (P=0.804), and the overall survival (OS) also did not differ significantly among the four groups (68.3%, 61.5%, 65.6%, and 63.6%, respectively; P=0.929). When it came to the comparison between the ABO identical/minor incompatible group and the ABO major/bidirectional incompatible group, the DFS (63.4% versus 60.5%; P=0.995) and OS estimates (65.7% versus 65.1%; P=0.820) were not significantly different, either. What’s more, none of the patients clinical developed severe immune hemolysis or pure red-cell aplasia after transplantation.In summary, the results above indicated that :1) ABO incompatibility did not seem to have a significant impact on clinical outcomes after UCBT, such as engraftment, transfusion requirements and survival. 2) No patients developed pure red-cell aplasia after UCBT. 3) In addition, we also compared the outcomes between the ABO-identical and bidirectional ABO-incompatible groups, even it did not show any significant difference, the former did better on platelet engraftment (81.7% versus 63.6%) and DFS (67.1 versus 54.5%). The reason led to this result may be the lack of bidirectional ABO-incompatible recipients. Therefore, we’d better avoid selecting bidirectional ABO-incompatible in UCBT to improve the patients’ recovery and survival time. DisclosuresNo relevant conflicts of interest to declare.

The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Center's Analysis

The Impact of ABO Incompatibility in Allogeneic Stem Cell Transplant (ALLOSCT): A Retrospective Single Center's Analysis

Analysis of Donor and Recipient ABO Incompatibility and Antibody-Associated Complications after Allogeneic Stem Cell Transplantation with Reduced-Intensity Conditioning

Allogeneic hematopoietic stem cell transplantation (HSCT) can be performed across the ABO blood group barrier. The impact of ABO incompatibility on clinical outcome is controversial. A retrospective analysis of 310 patients who underwent HSCT with reduced-intensity conditioning between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-RBC antibodies in passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or recurring recipient type ABO antibodies (PRABO) after major ABO mm HSCT, and autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical outcome were analyzed by univariate and multivariate analysis for groups with or without anti-RBC antibodies. ABO blood group incompatibility did not affect clinical outcome despite an increased requirement of blood transfusion. Twelve patients with AIHA, 6 patients with PLS, and 12 patients with PRABO post-HSCT were identified. AIHA did not affect overall survival (OS) or transplant-related mortality (TRM), but patients with AIHA had a lower incidence of grades II to IV acute graft-versus-host disease (P = .05). OS in the PLS group was 0% compared with 61% in the whole group receiving minor ABO mm transplants (P < .001). Comparing PRABO patients with those receiving a major ABO mm HSCT, the OS was 17% versus 73% (P = .002) and TRM was 50% versus 21% (P = .03). At our center, PLS after minor ABO mm and PRABO antibodies after major ABO mm HSCT are significant risk factors for decreased OS and TRM. Our results suggest that occurrence of unexpected ABO antibodies after HSCT warrant a wider investigation individual to find the underlying cause.

Transfusion Requirements in Allogeneic Hematopoietic Cell Transplantation (HCT) Recipients Given Either Myeloablative or Nonmyeloablative Conditioning, and Effect of ABO Incompatibility on HCT Outcomes.

We retrospectively assessed 1) overall platelet (PLT) and red blood cell (RBC) transfusion requirements within the first 100 days after allogeneic among HCT recipients given either nonmyeloablative (n=365) or myeloablative conditioning (n=1430); 2) transfusion requirements among nonmyeloablative recipients given grafts from related (n=187) vs. unrelated donors (n=178), and grafts from ABO matched (n=203) vs. ABO mismatched donors (n=159); and 3) the impact of ABO incompatibility on HCT outcomes among nonmyeloablative recipients. Table 1 summarizes results. We confirmed that myeloablative recipients were more likely to receive both PLT and RBC transfusions than nonmyeloablative recipients (both p<0.0001). Subsequent analyses were restricted to nonmyeloablative recipients. Both PLT and RBC transfusion requirements were increased among recipients of unrelated grafts (both p<0.0001) and those with major or bi-directional ABO mismatched grafts (p = 0.019 and p=0.003, respectively). No statistically significant differences were observed in cumulative incidences of graft rejection/failure, grades II-IV acute GVHD and in 3-year survivals between ABO-matched, minor-mismatched, and major/bidirectional mismatched pts (p=0.89, 0.48, and 0.49, respectively). Times to disappearance of anti-donor IgM and IgG isohemagglutinins were not statistically significantly different among major or bi-directional ABO mismatched related (43 days for both) vs. unrelated recipients (58 and 57 days, p=0.20 and 0.27, respectively). Major/bidirectional ABO-mismatched recipients with grades II-IV vs. 0–I acute GVHD had comparable likelihoods of reaching IgM (p=0.20) and IgG (p=0.63) titer endpoints. In conclusion, nonmyeloablative pts had reduced PLT and RBC transfusion requirements compared to myeloablative pts. Among nonmyeloablative pts, unrelated (vs. related) grafts and ABO-incompatibility (vs. ABO compatibility) between donors and recipients led to increased PLT and RBC transfusion requirements. ABO incompatibility did not increase graft rejection nor GVHD or adversely affect survival after non-myeloablative HCT. The tempo of disappearance of anti-donor isohemagglutinin titers was not influenced by donor type or occurrence of GVHD.Table 1. Percentage of patients requiring at least one PLT or RBC transfusion.% of Patients Requiring TransfusionsNPLTp-value†RBCp-value†Non-myeloablative36536%*76%*Myeloablative143099%<0.000196%<0.0001Non-myeloablativeRelated grafts18725%*67%*Unrelated grafts17847%<0.000186%<0.0001Non-myeloablative£ABO-matched20333%*70%*ABO minor mismatched7933%0.9580%0.11Major bi-directional ABO-mismatched8048%0.01988%0.003Non-myeloablative ABO-mismatchedRelated grafts6632%*77%*Unrelated grafts9346%0.06888%0.067† p-value from Chi-square test.* Reference group for comparisons.£ Information were missing from 3 patients.

Impact of ABO incompatibility on engraftment and transfusion requirement after unrelated cord blood transplantation: a single institute experience in Japan

The impact of ABO incompatibility between donor and recipient on engraftment and transfusion requirement was studied in 95 adults who underwent unrelated cord blood transplantation (CBT). The patients included 27 ABO-identical, 29 minor, 21 major and 18 bidirectional ABO-incompatible recipients. Neutrophil engraftment did not differ between ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients (hazard ratio (HR) 1.17, P=0.48). Cumulative incidence of platelet engraftment in ABO-identical/minor ABO-incompatible recipients was higher than in major/bidirectional ABO-incompatible recipients (HR 1.88, P=0.013). In addition, fewer platelet transfusions were required during the first 60 days after CBT in ABO-identical/minor ABO-incompatible recipients (HR 0.80, P=0.040). RBC engraftment did not differ between the two groups (HR 1.25, P=0.33). However, fewer RBC transfusions were required in ABO-identical/minor ABO-incompatible recipients than in major/bidirectional ABO-incompatible recipients (HR 0.74, P<0.005). No patients developed pure red-cell aplasia after CBT. These results indicate that ABO incompatibility affected platelet engraftment and transfusion requirement of RBC and platelet in CBT recipients. Further studies including larger patient numbers are required to elucidate the impact of ABO incompatibility on the clinical outcome of CBT.

Impact of ABO incompatibility on outcome after allogeneic peripheral blood stem cell transplantation

Few studies have addressed the incidence of graft-versus-host disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median follow-up duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.0+/-9.0, 43.1+/-11.6, and 43.8+/-13.5%, respectively (P=0.8652), while the 3-year disease-free survival estimates were 33.8+/-7.6, 39.9+/-11.4, and 45.7+/-13.1%, respectively (P=0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLA-matched sibling donors.