ABO-incompatible Patients Research Articles

Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant.

ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis. A retrospective review of all patients who received an ABOi LT at ourinstitution was performed. Comparisons were made based on era (early: 1997-2008, modern: 2009-2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant. 17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1-28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1. ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.

Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts.

Pathologic diagnosis of antibody-mediated rejection (ABMR) in ABO-incompatible (ABOi) transplantation patients is often challenging because patients without ABMR are frequently immunopositive for C4d. The aim of this study was to determine whether C4d positivity with microvascular inflammation (MVI), in the absence of any detectable donor-specific antibodies (DSAs) in ABOi patients, could be considered as ABMR. A retrospective study of 214 for-cause biopsies from 126 ABOi kidney transplantation patients was performed. Patients with MVI score of ≥2 and glomerulitis score of ≥1 (n = 62) were divided into three groups: the absolute ABMR group (DSA-positive, C4d-positive or C4d-negative; n = 36), the C4d-positive group (DSA-negative, C4d-positive; n = 22), and the C4d-negative group (DSA-negative, C4d-negative; n = 4). The Banff scores, estimated glomerular filtration rates (eGFRs), and graft failure rates were compared among groups. C4d-positive biopsies showed higher glomerulitis, peritubular capillaritis, and MVI scores compared with C4d-negative specimens. The C4d-positive group did not show significant differences in eGFRs and graft survival compared with the absolute ABMR group. The results indicate that C4d positivity, MVI score of ≥2, and glomerulitis score of ≥1 in ABOi allograft biopsies may be categorized and treated as ABMR cases.

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.

423.11: Long-term Compromised Immune Regulation After Rituximab Induction in Blood Group Incompatible Living-Donor Renal Transplantation - 5 Year Results of a Prospective Pilot Study

Background: An increased frequency of severe infectious diseases and BK viremia has been described after ABOi renal transplantation. As rituximab induction may alter immunoregulation in these patients, we analyzed clinically relevant immune parameters in a prospective renal transplant study up to 5 years posttransplant. Materials and Methods: Mononuclear cell subsets (peripheral blood; lymph nodes taken during transplant surgery), intracellular cytokine responses, CD4 helper function and in-vitro B cell responses were assessed pretransplant and up to 5 years posttransplant in 85 renal transplant recipients (living donation: n=25 ABO incompatible (ABOi) and n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible). Results: Severe infectious diseases occurred more often in ABOi than ABOc recipients within 2 years posttransplant (11/24 (46%) versus 6/30 (20%), P=0.042) but not beyond. The incidence of BK viremia was significantly enhanced in rituximab versus non-rituximab treated patients (1 year: 9/29 (31%) versus 4/54 (7%), P=0.009; 5 years: 10/30 (33%) versus 7/53 (13%), P=0.029). After rituximab induction in ABOi recipients, counts of peripheral blood B cell subsets were profoundly downregulated even 3 years posttransplant and reached the level of non-ABOi recipients after 4 years (memory B cells after 5 years). T-dependent and T-independent B cell responses were significantly impaired in ABOi patients up to 2 years posttransplant (P=0.010 and P=0.053, respectively) whereas CD4 helper activity was not compromised. CD4+ T cell counts were significantly lower in ABOi compared to ABOc recipients at 3 and 6 months (P=0.025 and P=0.046, respectively), but showed no differences in the percentage of Tregs. In regional lymph nodes of ABOi patients, we found a significant downregulation of CD20+ but not CD19+ B cells (P<0.0005), of naive B cells (P=0.031) and short lived plasma cells (P<0.0005) at the time of transplantation. Conclusion: An increased frequency of severe infectious diseases and BK viremia in rituximab treated ABOi renal transplant recipients may be explained by significantly downregulated CD4+ T cell counts up to 6 months and a profoundly delayed B cell repopulation, most pronounced with regard to memory B cells, together with compromised B cell responses up to 2 years posttransplant. IL-10, as a key player in chronic BK virus infection, was not upregulated in rituximab-treated ABOi transplant recipients.

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.

Infection Risk in the First Year After ABO-incompatible Kidney Transplantation: A Nationwide Prospective Cohort Study.

ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised. In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection. We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461). The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.

Isoagglutinin Titers in ABO-Incompatible Kidney Transplant

A decrease in the isoagglutinin titer <1:8 is usually required for ABO-incompatible (ABOi) transplantation and the presence of high predesensitization titers may condition future transplantation. The aim of the study was to analyze the prognosis of ABOi patients undergoing desensitization and to compare the results according to the baseline isoagglutinin titer. ABOi patients transplanted in our center after desensitization with rituximab, apheresis (plasmapheresis, immunoadsorption with Glycosorb, or both) and immunoglobulins were studied. Survival, renal function, and complications were analyzed and the results were compared according to the presence of a baseline isoagglutinin titer higher or lower than 1:128. We analyzed 48 patients (34 male) with a mean age of 50.9 ± 11 years and a mean follow-up of 44.6 ± 30 months. Thirty-eight patients had a basal isoagglutinin titer ≤1:128 and 10 had a titer >1:128. We did not observe differences in patient survival: 96% vs 100% at 5 years (P=.64) and renal survival: 91% vs 100% at 5 years (P=.39), incidence of acute rejection: 13.2% vs 0% (P=.22), infectious complications (cytomegalovirus; 16% vs 30%, P=0.30; Polyomavirus BK virus: 13% vs 0%, P = .22), or surgical (hematoma): 47% vs 60% (P=.47) between the 2 groups. A higher number of apheresis sessions was observed (4.8 ± 1.9 vs 10.9 ± 3.9; P=.001); use of both techniques (0% vs 100%, P < .001) and higher processed volume (1 ± 0.1 vs 1.4 ± 0.5; P=.049) in patients with titer >128 was observed. Creatinine and proteinuria were similar and not significant. Baseline isoagglutinin titer does not influence the prognosis of ABOi patients after desensitization. The number of sessions required to achieve baseline titer <1:8 is higher but does not influence the number of days of hospital admission.

Excellent outcome following emergency deceased donor ABO-incompatible liver transplantation using rituximab and antigen specific immunoadsorption

Background The acceptance of ABO-incompatible (ABOi) liver grafts will expand the donor pool for a patient in urgent need for a liver transplantation (LT). Here we report our results with emergency ABOi DD (deceased donor) LT using rituximab and antigen specific immunoadsorption. Patients and Methods 2009 to 2019 we performed 20 ABOi DD LTs (adults n = 17, children n = 3) for patients in urgent need for a LT. Immunosuppression consisted of rituximab (n = 20) and basiliximab (n = 15) or anti-thymocyte globuline (n = 4), intravenous immunoglobulin (IVIG; n = 6), tacrolimus, prednisolone and mycophenolate mofetil. Fifteen patients were treated with IA (n = 14) or both IA and plasmapheresis (PP; n = 1) pre-transplant and 18 patients were treated with IA (n = 15) or both IA and PP (n = 3) post-transplant. The median pre-transplant MELD- score was 40 (range 18–40). Patient and graft survival and complications were compared to a 1:4 case matched control group of ABO-identical or compatible (ABOid/c) DDLT. Results The 1-, 3- and 5-year patient and graft survival rates were 85, 85 and 78% for the ABOi recipients and not significantly different compared to ABOid/c controls. Only one ABOi patient developed antibody-mediated rejection. Conclusion Patient and graft survival after emergency ABOi DDLT using rituximab and immunoadorption was equal to ABOid/DDLT. ABOi DD LT was a successful approach to expand the donor pool for patients in urgent need for a liver graft.

Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BackgroundWith the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT.Material/MethodsFrom March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis.ResultsPatient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01).ConclusionsMicroscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

One-Year Outcomes of Living Related Kidney Transplant in Patients With Preformed HLA Donor-Specific Antibodies: A Single-Center Experience in Malaysia

The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients.This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant.A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups.Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort.

P147 Decreasing medicare cost by tailoring single antigen test utilization on renal allocation score

Aim There are currently 95,121 patients awaiting a renal transplant in the US (UNOS data). The average cost of combined testing for HLA class I and II by single antigen (SA) is around $900. If all renal patients were screened monthly this would translate in over $1 billion in annual Medicare costs. We investigated whether cost saving could be achieved by devising a test utilization strategy based on patients’ UNOS status and allocation score. Methods First, we performed a query in UNET to obtain the renal allocation score and status (1 active or 7 inactive) of all renal transplant patients listed at our center. Second, we performed a search of all kidneys allocated by our OPO in the last 3 months to determine what allocation category and patient renal allocation score received the kidneys. Results Of the 588 patients on our waitlist, 65.3% were listed active and 34.7% were listed inactive. The average allocation score for kidneys placed by our OPO in the last 3 months was 7.27 for the first allocated kidney and 5.64 for the second kidney (scores above 15 were excluded). 8.4% of first allocated kidneys were transplanted in patients with scores below 4. These included ABO incompatible (A2 into B), 0-ABDR mismatch, and pediatric patients. Only one kidney with a KDPI of 35–85% was allocated to a patient with less than 4 points. A greater proportion of second kidneys were transplanted in patients with lower scores particularly 86–100 KDPI kidneys, kidney with long ischemic times, and high risk donors. Based on these results we developed a testing strategy whereby patients which are listed status 7 do not get tested by SA. Status 1 patients with less than 4 points are tested annually and those with more than 4 points are tested quarterly. Utilization of this testing strategy has resulted in a saving of 87.9% vs monthly testing. Conclusions It is possible to devise an SA test utilization strategy based on the listing status and allocation score of renal patients. We recognize that this approach may need to be tailored to each center depending on local allocation data and each center’s transplant practice. However, using such strategy can significantly decrease Medicare cost. When compare to monthly screens, we calculated that if used nationwide our approach could yield annual savings to Medicare of up to $902,810,700.

Pronase independent flow cytometry crossmatching of rituximab treated patients

ABO-incompatible (ABOi) kidney transplantation has become an established strategy to increase the number of available living donors. At our center, the conditioning protocol for ABOi patients is based on anti-A/B antibody removal and depletion of B cells with the anti-CD20 mAb rituximab (Mabthera®). It is known that even low amounts of remaining rituximab in serum of patients results in false positive B cell cross match results, masking detection of potentially harmful donor human leukocyte antigen (HLA) specific antibodies. Treatment of donor cells with high concentrations (>1 mg/mL) of pronase is currently standard procedure for elimination of rituximab (RIT) interference. It is, however, troublesome that recent reports indicate that pronase treatment per se can induce incorrect flow cytometry cross match (FCXM) results. The aim of this study was to evaluate an alternative pronase-free FCXM for crossmatching of patients treated with rituximab.FCXM with an anti-RIT monoclonal antibody (mAb) pre-blocking step were evaluated on normal human sera (NHS) and patient sera supplemented with RIT. NHS supplemented with RIT or patient sera, without donor specific antibodies (DSA), resulted in high B cell median channel shift (>200 IgG) above background. This shift was eliminated by a serum pre-blocking step with 2-fold excess of anti-RIT (clone MB2A4). Blocking with anti-RIT did not influence the T cells crossmatch results. We present data supporting proof-of-concept that blocking with anti-RIT antibody prior to XM can enable reliable detection of anti-HLA class I and II donor specific antibodies without use of pronase treated donor cells.

Extracorporeal Membrane Oxygenation Support for Rituximab-Induced Acute Respiratory Distress Syndrome in an ABO-Incompatible Living Donor Liver Transplant Recipient: Successful Management of a Rare Complication and a Review of the Literature

BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO-incompatible liver transplant recipients. Although well-tolerated, rituximab infusion therapy may result in severe pulmonary adverse effects such as drug-induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which has a high mortality rate. Management of such rare cases in an ABO-incompatible patient has never been described before. Herein, we present successful use of extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in an ABO-incompatible living donor liver transplantation (LDLT) recipient. CASE REPORT A 57-year-old man patient presented with acute-on-chronic hepatic failure. Due to worsening clinical condition and unavailability of a deceased donor organ, ABO-incompatible LDLT was considered. The patient received rituximab therapy and plasmapheresis 1 week before the transplantation to reduce the B cell count. However, he suddenly developed acute respiratory distress-like symptoms, with a chest X-ray suggesting organized pneumonia. Infectious etiology was excluded as evidenced from negative sputum and blood culture, which were repeated after 48 h. LDLT was performed and ECMO support was instituted in the immediate postoperative period due to worsening of the ARDS. The pulmonary signs improved, with a chest X-ray showing clear lung fields on the 5th postoperative day. The patient recovered well and was discharged with normal liver functions in the 4th postoperative month. CONCLUSIONS This is first reported experience of successful use of ECMO in an ABO-incompatible liver transplant recipient with rituximab-induced ARDS. This experience shows the feasibility and effectiveness of ECMO support in liver transplant recipients with poor respiratory functions.

Safety; efficacy and adverse effects of therapeutic plasma exchange in a tertiary care centre; in ABO incompatible transplant patients

Safety; efficacy and adverse effects of therapeutic plasma exchange in a tertiary care centre; in ABO incompatible transplant patients

Successful Kidney Transplantation After Stepwise Desensitization Using Rituximab and Bortezomib in a Highly HLA-Sensitized and ABO Incompatible High Titer Patient.

Highly sensitized patients receive fewer kidney transplants and have a high risk for severe rejection, with increased rates of graft loss. We encountered a highly HLA-sensitized and ABO-incompatible patient with an extremely high antiblood group titer who underwent kidney transplantation successfully after a 2-year-long challenging desensitization therapy.

Study on Serological Blood Group Conversion in BM Empty Phase of ABO-incompatible Allogeneic Stem Cell Transplantation

To explore the regularity of serological conversion of blood group in BM empty phase of ABO-incompatible allogeneic stem cell transplantation so as to provide the basis for selecting the blood components in blood transfusion. Before hematpoietic stem cell transplantation (HSCT), the ABO and RhD blood groups of recipients and donors were identified by salt medium tube method and microcolumn gel method; after transplantation the changes of antigen intensity and antibody titer of ABO blood group in patients were periodically detected. After blood group shift of 33 patients received ABO-incompatible allo-HSCT, the consistent rate of positive and regative types in major ABO incompatible group was 100%; the consistent rate of positive and negative types in minor ABO-incompatible group was 33%, no-consistent rate was 66.7%; the consistent rate of positive and negative types in bidirextional ABO incompatible group was 20%, the no-consistent rate was 80%. After ABO-incompatible allo-HSCT, blood group antgen of patients shifts to the blood group of donors, there is a significant difference in the serological indicators between the minor and bidireetional ABO-incompatible patients and normal people.

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.

Spontaneous clearance of hepatitis C virus after liver transplantation: a report of four cases

End-stage liver disease associated with hepatitis C virus (HCV) infection is the leading indication for liver transplantation. Hepatitis C virus infection recurrence in the graft is common under immunosuppression, leading to an accelerated rate of graft failure. We report the clinical features of four of our patients: three patients presenting with spontaneous hepatitis C virus clearance after liver transplantation and one presenting with transient disappearance of hepatitis C virus postoperatively. The transitional period from surgery to hepatitis C virus clearance was <5 months for all patients. The immunosuppression therapy included tacrolimus, mycophenolate mofetil, and corticosteroids. One ABO-incompatible patient presented spontaneous viral clearance postoperatively for the last 5 years. Two patients had episodes of severe bacterial infection, which resulted in a temporary reduction of immunosuppression. Two patients presented with a transient elevation of transaminase preceding spontaneous hepatitis C virus clearance. These clinical findings suggested that factors including surgical stress, severe bacterial infection, and temporary interruption of immunosuppression were correlated with the reactivation of nonspecific immune responses in the hosts, resulting in spontaneous hepatitis C virus clearance postoperatively.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption

For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

De novo mTOR inhibitor-based immunosuppression in ABO-incompatible kidney transplantation.

ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low-dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three-yr follow-up treated with this regimen. Three-yr patient survival and graft survival were 96% and 83%. The rate of acute T-cell-mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor-based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.