ABO-incompatible Transplantation Research Articles

Double filtration plasmapheresis for children with different types of critical kidney diseases: a single-center retrospective cohort study.

Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

Living donor liver transplant: A strategy to increase transplant access

Living donor liver transplant: A strategy to increase transplant access

Outcomes of abo-incompatible kidney transplantation: Novel ways of reducing rejection, complications, and cost

AimOur objective was to report the outcomes of ABO-incompatible (ABOi) transplants and seek solutions to pretransplant desensitization, peri and postoperative bleeding events, acute rejection and infection-related mortality. MethodsWe retrospectively analyzed 247 consecutive ABOi kidney transplantations at our center from June 2012 to March 2020. The primary outcomes were patient, graft, and death-censored graft survival over 5 years. ResultsA total of 31 patients received thymoglobulin and 216 patients received basiliximab induction. Patient survival rates with basiliximab induction at 1, 3, and 5 years were 97.8%, 93.5%, and 93.5%, respectively; corresponding graft survival rates were 95.1%, 86.6%, and 85.2%, respectively. Overall, biopsy-proven acute rejection occurred in 11.7% recipients; primarily due to antibody-mediated rejections. Cumulative incidence of graft loss was 7.5% at 5 years and overall incidence of death was 6.07%. ConclusionReplacement of filtered plasma by donor group fresh frozen plasma rather than albumin reduced bleeding, IVIG administration, number of plasmapheresis sessions and the need for filters. Thymoglobulin avoidance decreased acute rejection rates. Rapid reduction and lower doses of prednisolone and MMF reduced infectious complications. These steps can help reduce rejection rates, complications and cost (up to USD 7000) comparable to ABO compatible transplantation in other centers as well.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic stricture

BackgroundGrafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). MethodsA total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. ResultsA progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. ConclusionsTransplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.

Progress in perioperative management of ABO-incompatible pediatric liver transplantation

ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

Pretransplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation.

Intrahepatic cholangiopathy is a life-threatening sequela of ABO-incompatible liver transplantation. We analyzed the clinical impact of pretransplant administration of mycophenolate mofetil in reducing intrahepatic cholangiopathy in ABO-incompatible liver transplantation. Patients who underwent living donor liver transplantation between 2010 and April 2022 were included. Pretransplant mycophenolate mofetil was started in November 2020. A comparison between patients who experienced intrahepatic cholangiopathy and who did not among ABO-incompatible transplantation was performed. Recipients of ABO-incompatible transplantations were categorized based on donor surgery into open, laparoscopy without pretransplant mycophenolate mofetil, and laparoscopy with pretransplant mycophenolate mofetil groups. Cox analysis of intrahepatic cholangiopathy was performed. A total of 234 ABO-incompatible transplantations were included. Intrahepatic cholangiopathy occurred in 1.1% (n=1/94), 13.3% (n=12/90), and 2.0% (n=1/50) of patients who received an ABO-incompatible liver with open surgery, laparoscopic donor surgery without pretransplant mycophenolate mofetil and laparoscopic donor surgery with pretransplant mycophenolate mofetil. ( p = 0.001) Multivariable analysis showed that transplantations involving a donor who underwent a laparoscopic hepatectomy and a recipient who did not receive pretransplant mycophenolate mofetil were associated with a higher risk of intrahepatic cholangiopathy (HR=13.449, CI=1.710-105.800, p = 0.02) compared with transplantations from donors who underwent open surgery. Transplantations involving a donor who underwent laparoscopic donor surgery and a recipient who received pretransplant mycophenolate mofetil resulted in no increased risk compared with transplantations from donors who underwent open surgery. (HR=5.307, CI=0.315-89.366, p = 0.25) Laparoscopic donor hepatectomy was a risk factor for intrahepatic cholangiopathy in ABO-incompatible liver transplantation, while pretransplant mycophenolate mofetil was related to risk reduction of intrahepatic cholangiopathy.

Impact of pretransplant asplenia vaccination on anti‐A/B antibody titers in prospective ABO incompatible kidney transplant recipients

AbstractBackgroundAsplenia vaccination is employed before ABO‐incompatible (ABOi) transplantation in case splenectomy is needed. Pneumococcal vaccines have been reported, in different patient groups, to increase anti‐A/B titers, through cross‐reactivity to shared polysaccharide epitopes. We investigated the impact of pretransplant asplenia vaccinations on anti‐A/B antibody titers in prospective ABOi renal transplant recipients.MethodsPublished asplenia vaccine microbial structures were reviewed to assess expression of A/B antigens. All patients who underwent ABOi transplantation at Monash Medical Centre with anti‐A/B titers taken either side of asplenia vaccination were included in a retrospective cohort study between 2007 and 2021. Patients with paired titers without intervening vaccination were included as controls. Paired titers were compared within groups.ResultsA and B antigens were found to be expressed by vaccine specific pneumococcal serotypes. Thirty‐nine ABOi renal transplant recipients received vaccination including at least one pneumococcal vaccine. The most common donor to recipient combination was A1 to O. The median pre‐ and postvaccination anti‐A/B titers were 1:32 and there was no significant change in titers following vaccination (median change in titer 0 dilutions, range –2 to 3, P = 0.43). The same findings were apparent in the control group (n = 20). There was no significant change in titer by donor blood group or vaccine type. No transplants were canceled or delayed by a rise in anti‐A/B titers postvaccination.ConclusionPneumococcal vaccination had no clinically relevant impact on anti‐A/B titers before ABOi transplantation in this cohort. These results provide reassurance regarding the safety of asplenia vaccination before ABOi transplantation.

Clinical Impact of Recipient-Derived Isoagglutinin Levels in ABO-Incompatible Hematopoietic Stem Cell Transplantation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). We hypothesized that recipient-derived isoagglutinin (RDI) levels could play a critical role in clinical outcomes. In this study, we compared clinical outcomes such as survival, GVHD, infection, relapse, transfusion, and engraftment, among ABO-compatible patients (ABOc), ABO-incompatible patients (ABOi) with low RDI, and ABOi patients with high RDI. The ABOi with high RDI group was defined as recipients with more than 1:16 RDI levels. We analyzed 103 recipients (ABOc, 53; ABOi with low RDI, 36; ABOi with high RDI, 14). The ABOi with high RDI group showed a decreased 1-year survival and increased acute GVHD grade IV and RBC transfusion (p = 0.017, 0.027, and 0.032, respectively). The ABOi with high RDI group was an independent risk factor for increased death, RBC transfusion, and poor platelet (PLT) engraftment (odds ratio (OR) = 3.20, p = 0.01; OR = 8.28, p = 0.02; OR = 0.18, p = 0.03, respectively). The ABOi with high RDI group showed significantly delayed PLT engraftment. In conclusion, this is the first study underscoring high RDI levels as a marker predicting unfavorable outcomes in ABOi HSCT.

The First ABO Incompatible Kidney Transplantation without Splenectomy in India - A Review at 12 Years.

The First ABO Incompatible Kidney Transplantation without Splenectomy in India - A Review at 12 Years.

ABO incompatible paediatric liver transplantation: Short term outcome from a single centre experience

ABO incompatible paediatric liver transplantation: Short term outcome from a single centre experience

Comparison of Total and IgG ABO Isoagglutinin Titers in ABO-Incompatible Organ Transplant Patients: Analysis of Data from a University Hospital Over the Last 5 Years

Comparison of Total and IgG ABO Isoagglutinin Titers in ABO-Incompatible Organ Transplant Patients: Analysis of Data from a University Hospital Over the Last 5 Years

ABO-Incompatible Liver Transplantation under the Desensitization Protocol with Rituximab: Effect on Biliary Microbiota and Metabolites.

Background: ABO-incompatible liver transplantation (ABOi LT) under the desensitization protocol with rituximab had excellent survival outcomes comparable to those of ABO-compatible liver transplantation (ABOc LT). In this work, we explored the effect of ABOi LT on recipients from the perspective of biliary microbiota and metabonomics. Methods: Liver transplant (LT) recipients treated at our center were enrolled in the study. In total, 6 ABOi LT recipients and 12 ABOc LT recipients were enrolled, and we collected their bile five times (during LT and at 2 days, 1 week, 2 weeks and 1 month after LT). The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. Results: We obtained 90 bile samples. Whether in group ABOi LT or ABOc LT, the most common phyla in all of the samples were Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The most common genera were Lactobacillus, Weissella, Klebsiella, Pantoea and Lactococcus. There was no significant difference in the diversity between the two groups at 1 week, 2 weeks and 1 month after LT. However, the biggest disparities between the ABOi LT recipients and ABOc LT recipients were observed 2 days after LT, including increased biodiversity with a higher ACE, Chao1, OBS and Shannon index (p < 0.05), and more Staphylococcus in ABOi LT and binary−Jaccard dissimilarity, which indicated varying β-diversity (p = 0.046). These differences were not observed at 1 week, 2 weeks and 1 month after LT. The principal coordinate analysis (PCoA) revealed that the composition of the bile microbiota did not change significantly within 1 month after LT by longitudinal comparison. In an analysis of the bile components, the metabolites were not significantly different every time. However, four enrichment KEGG pathways were observed among the groups. Conclusion: These findings suggest that ABOi LT under the desensitization protocol with rituximab did not significantly affect the biliary microbiota and metabolites of recipients.

Late Onset of Pneumocystis jirovecii Pneumonia in Kidney Transplant: How Long is too Long in Opportunistic Infection Prophylaxis?

Pneumocystis jirovecii (PJ) opportunistic infections occur in immunocompromised patients impacting significantly hospitalizations and mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) is universally used as prophylaxis of Pneumocystis jirovecii pneumonia (PJP) and therefore, this infection is rare condition in solid organ transplant (SOT) recipients. We present a case of a 46-years-old male, who received an ABO-incompatible transplant with prior desensitization protocol with plasmapheresis, rituximab, and anti-CMV immunoglobulin. IgG anti-B title pre-desensitization was 1:128. The patient had 6 ABDR mismatches, without HLA antibodies, and the CDC crossmatch for T and B cells was negative. Both recipient and donor were CMV positive (D+/R+). The patient received induction immunosuppression with corticosteroids, basiliximab, calcineurin inhibitor, and mycophenolate mofetil. Immediate kidney function was verified, and three additional plasmapheresis sessions were performed. At discharge serum creatinine (sCr) was 1.38 mg/dL, but kidney function declined during the first 6 months (sCr 2.5 mg/dL). Urinalysis was unremarkable. A kidney biopsy was declined by the patient. Unit protocol maintained the prophylaxis for PJP and cytomegalovirus (CMV) infection with TMP-SMX and valganciclovir. The patient was admitted to the emergency department 20 months after the transplant with respiratory symptoms and was diagnosed with PJP. Bronchoalveolar lavage fluid was also positive for CMV. Intensive care unit (ICU) admission was necessary due to clinical deterioration, with subsequent good evolution without mechanical ventilation. At discharge, prophylaxis with TMP-SMX and valganciclovir was maintained for more than six months. Here we discuss the late onset of PJP, and the main risk factors related to severe infection. Transplant subgroups in which longer PJP prophylaxis could be beneficial and the indication to re-start PJP prophylaxis is still under discussion.

The fate of donor-type ABO blood group antigen expression in liver grafts in ABO-incompatible adult living donor liver transplantation.

Donor-type ABO blood group antigens (dABOAgs) have been detected in ABO-incompatible adult living donor liver transplantation (ABOi ALDLT) grafts, but their fate and role in ABOi ALDLT rejection remain uncertain. The 0-day, <1-month, and 1-year serial liver graft biopsies from 30 ABOi ALDLT recipients were retrospectively evaluated. ABO antigen expression was quantitatively and serially measured by the mean number of positively stained vascular structures (endothelium of the capillaries, arteries, hepatic veins, and portal veins) within the portal tracts (sS). The dABOAg sS counts of 0-day, <1-month, and 1-year liver graft biopsies (32.3, 20.8, and 20.6, respectively) decreased significantly (p < .001). Early rejection in the <1-month biopsy was observed in 8/30 (26.7%) recipients, four (13.3%) of whom showed antibody-mediated rejection. The sS counts tended to rebound in grafts showing early rejection, with minimal changes from the 0-day to <1-month period, but increased to pre-transplantation levels after 1year, compared to that in grafts without early rejection (36.0, 20.4, 19.6 vs. 23.7, 21.9, 23.0, respectively; p=.040). While dABOAg expression decreased after ABOi ALDLT, recipients showing early rejection showed sustained graft dABOAg expression. Therefore, dABOAg expression may be involved in the mechanism of accommodation in ABOi transplantation.

ABO-incompatible renal transplant: a single center experience from India

Vaibhav Tiwari, Nikita Pawar, Anurag Gupta, Shiv Chadha, Vinant Bhargava, Manish Malik, Ashwani Gupta, Anil Kumar Bhalla, Devender Singh Rana. Korean J Transplant 2022;36:26. https://doi.org/10.4285/ATW2022.F-1208

Posttransplant plasma exchange prevents hepatocellular carcinoma recurrence in ABO-incompatible liver transplantation: propensity-matched analysis

Posttransplant plasma exchange prevents hepatocellular carcinoma recurrence in ABO-incompatible liver transplantation: propensity-matched analysis

Optimal blood transfusion strategy in ABO-incompatible sold organ transplantation patients: perspective of passenger lymphocyte syndrome

Optimal blood transfusion strategy in ABO-incompatible sold organ transplantation patients: perspective of passenger lymphocyte syndrome

ABO-incompatible Pediatric Liver Transplantation With Antibody and B-cell Depletion-free Immunosuppressive Protocol in High Consanguinity Communities.

From November 2010 to June 2015, 176 children aged 0.2-to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered. The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5-70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures. ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.

A study of blood group conversion in patients with ABO incompatible hematopoietic stem cell transplantation—A decade survey

BackgroundABO incompatibility is not a contraindication but would affect the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The dynamic change of blood phenotype is not only related to the patient's status, but also the basis for the implementation of compatible blood transfusion. The criteria for judging a complete transformation to donor-type and the principle of blood transfusion at relapse need to be unified. We aimed to illustrate the significance of blood group monitoring after allo-HSCT. Material and methodsWe collected 263 patients underwent ABO incompatible allo-HSCT from January 2010 to December 2019, and monitored blood type regularly according to the frequency of the patient's return visits till complete conversion or death. Non-parametric test was used to find differences among incompatible groups. We analyzed factors potentially influence blood type conversion by Binary Logistic model. Cox regression model was used to illustrate the relationship between blood-type conversion and prognosis. ResultsThe median days of conversion were 107, 91 and 108 in major-, minor- and bidirectional groups respectively. Blood type conversion correlated with HLA compatibility (P = 0.012, OR=2.69) and acute graft-versus-host-disease (P = 0.001, OR=0.06). Patients with incomplete blood type conversion had a higher death rate than those with complete blood type conversion(P = 0.003, OR=3.703). DiscussionBlood type monitoring can help to evaluate the prognosis of transplantation and assess the risk of death. It is recommended to monitor the changes of blood group antigens and antibodies, especially within a year after transplantation, to predict the risk of adverse events (such as GVHD, recurrence, death, etc.).