ABO-incompatible Patients Research Articles

Biliary Complications After 52 Adult Living Donor Liver Transplantations: A Single-Center Experience

Objective The incidence of biliary complications after adult living donor liver transplantation (ALDLT) are still high even though various devices have been reported to overcome them. Method From October 2000 to April 2007, we performed 52 ALDLTs which included 15 ABO-incompatible grafts. Median follow-up was 565 days. In 49 procedures, we used duct-to-duct anastmosis with a stent inserted in the recipient duct and out through the common bile duct wall as an external stent, and in 3 procedures, we used duct-to-jejunostomy anastomosis. We investigated postoperative biliary complications and their management. Results Forty-four patients received right lobe grafts and 8 received left lobe grafts. Among patients in whom duct-to-duct anastomosis was used, nine (20.5%) developed biliary complications including bile leakage in five and biliary strictures in four. All bile leakage was treated with reoperation. Three biliary strictures were treated with stent placement, and one biliary stricture was treated with magnetic compression anastomosis. Among the three patients in whom duct-to-jejunostomy was used, two (66.7%) had bile leakage and stricture, respectively. Two of four ABO-incompatible patients (50%) had hepatic artery thrombosis with biliary complications, a high incidence. Conclusion In our series of ABO-incompatible patients undergoing ALDLT, those who developed hepatic artery thrombosis exhibited a high incidence of biliary complications.

Successful Rescue of Refractory, Severe Antibody Mediated Rejection with Splenectomy

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

Plasmapheresis in nephrology: an update

In the past, recommendations for the use of plasmapheresis were based on findings reported from pilot studies or anecdotes. New results from several randomized controlled trials have changed the indications for the use of plasma exchange. A large randomized controlled study of patients with antineutrophil cytoplasmic antibody associated vasculitis showed benefit of plasmapheresis in those with severe renal disease. Patients receiving plasmapheresis compared with methylprednisolone as adjuvant therapy were more likely to be alive and dialysis independent. Plasmapheresis, following publication of a recent randomized controlled trial, should no longer be used for patients with myeloma and acute renal failure. Standard therapy with five to seven plasma exchanges was compared with standard therapy alone. There was no difference in those patients reaching the composite endpoints between the two treatments. New indications include desensitization protocols, using plasmapheresis and intravenous immunoglobulin, which have allowed transplantation across immunological barriers. Highly sensitized patents and ABO incompatible patients compared with their potential donors are now being transplanted with excellent results. Studies still need to be done to assess the best desensitization protocol. The use of plasmapheresis requires further validation by randomized clinical trials. Recent published trials should alter practice but further studies are required.

ABO-Incompatible Living Donor Transplantation: Is It Economically “Compatible”?

The organ shortage remains the most serious constraint in transplantation. Living donor transplantation may be the most important strategy to reduce the organ shortage in kidney-transplantation. ABO blood antigen incompatibility is prime factor preventing living donor transplantation from reaching i

The Comparison of Myeloablative Versus Reduced Intensity Conditioning Regimen in ABO Mismatched Allogeneic Hematopoietic Cell Transplantation.

Recently, in an effort to reduce the transplant related mortality, AHCT with reduced intensity conditioning (RIC) have been developed. It has been reported that patients receiving RIC from an ABO-mismatched donor had more transplant-associated complications compared to ablative AHCT (BMT 2001; 28: 315, Transfusion 2002; 42:1293, Transfusion 2003; 43: 1153). In this single center, retrospective, historical case-matched study, we aimed to analyze the influence of ABO-incompatibility on transplant-related morbidity and mortality between ablative and RIC. Between 1988 and 2003, 39 patients underwent AHCT with RIC and only 14 were ABO-incompatible. Ten patients with ABO-incompatibility and having a regular follow-up for blood group typing were evaluated for immuno-hematological complications, such as acute or delayed-type hemolysis (DTH), pure red cell aplasia (PRCA), thrombotic thrombocytopenic purpura (TTP) and early transplant-related complications, were compared to 20 case control recipients having matched pretransplant characteristics and similar follow up, but myeloablative regimen, either bone marrow (BM) or peripheral blood (PB) stem cells infused. Patients' characteristics are shown in table below. All the recipients and donors underwent a detailed pretransplant work up and all the recipients were followed twice a week post transplant by a transfusion specialist according to guidelines (BMT , 2001; 28:315). Median follow-up was 195 days (range, 51–538d). We did not observe any acute hemolysis, but 11 experienced DTH. No significant differences were encountered among the three groups in terms of DTH (p=0.356). In all recipients having a major ABO incompatibility, the blood group switched to donor type, but 50% of the patients with minor ABO-incompatibility still had either their antigen persistency or the appearance of donor-derived isoagglutinins. We observed mild (n=1, BM group) and severe pure red cell aplasia (n=1, RIC group) in two patients having a major ABO-incompatibility. TTP was developed in one patient with major ABO-incompatibility. In conclusion, we did not observe any difference between ablative AHCT and RIST in ABO incompatible patients in terms of immuno hematological complications in contrast to published case series. In addition, we could not show any negative impact of ABO-incompatibility on the severity of acute GVHD and the rate of early transplant related mortality.TableConditioningAblativeReduced IntensitySource (patients)PB (n=10)BM (n=10)PB (n=10)Gender (M/F)2/86/45/5Median age (range)34 (16–45)31 (17–46)33 (21–47)DiagnosisCML (2), AML (7), other (1)CML (2), AML (6), other (2)CML (4), AML (1), other (5)ABO-incompatibilityMajor565Minor545Delayed type hemolysis5 (50%) (22,23,55,90,120)2 (20%) (18,27)4 (40%)(20,130,165,188)RBC transfusion (100 days)3 (0–15)4 (0–10)5 (0–10)Median days of the independence from pRBC7 (0–31)18 (0–41)7 (0–28)Median follow-up (days)195 (90–538)194 (63–467)200 (51–511)Acute GVHD (grade II–IV) n (%)3 (30%)4 (40%)4 (40%)TRM 100, n (%)1 (%10)1 (%10)1 (%10)

Pediatric Heart Transplantation: Improving Results in High-Risk Patients

Our institutional experience with 68 pediatric patients undergoing cardiac transplantation was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. The introduction of donor blood insulin cardioplegia was associated with a significant improvement in patient and graft survival. Among 63 ABO-matched transplant procedures, both the patient and graft loss rate were significantly lower (by multivariable analysis) with the use of the donor blood insulin cardioplegia versus conventional cardioplegia, despite significantly longer ischemic times in the former group. Twenty-three (33.8%) patients were deemed at ultra-high risk: eight of 11 patients with cardiomyopathy transplanted following ECMO support survived without major sequelae; three of four additional patients survived early retransplantation. Ten patients underwent intentional ABO-incompatible transplantation under a protocol of plasma exchange on bypass. There were two early deaths because of nonspecific graft failure and respiratory complications with mild vascular rejection, and one late death because of lymphoma. Among seven surviving ABO-incompatible patients followed up to 31 months, there have been no episodes of humoral rejection despite development of antidonor blood group antibodies in A to O, but not B to O, mismatches. The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting salvage of patients conventionally considered at high risk or nontransplantable.

Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies by double filtration plasmapheresis.

Successful clinical ABO-incompatible renal transplantation has been achieved by the removal of anti-A or anti-B antibodies using double filtration plasmapheresis (DFPP). We have compared changes in the levels of anti-donor antibodies and the histopathology of the renal grafts following human ABO-incompatible allotransplantation and pig-to-baboon xenotransplantation using pretransplant DFPP. DFPP was performed on days 6, -4, -2 and -1 before the ABO-incompatible transplants (n=25) and on days -2 and 0 (immediately before reperfusion) in the xenotransplants (n=4). In two baboons (XenoTx Group I) the extent of antibody removal was comparable to that in the ABO-incompatible patients, and an even greater level of removal was achieved in another two baboons (XenoTx Group II). Anti-A and anti-B and anti-pig IgM and IgG antibodies were measured by flow cytometry. All clinical ABO-incompatible renal grafts are functioning, except two which were lost from recurrence of the original disease or from chronic rejection. Three other grafts underwent humoral rejection episodes, which were successfully treated. DFPP reduced the mean anti-A/B IgM and IgG antibody levels to 8% and 13% of pretreatment levels, respectively. After kidney transplantation, they were maintained at 37% and 46% of pre-DFPP level. No antibody binding to the transplanted kidney was detected at any time (1 h to 2 yr) after ABO-incompatible allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody removal (90%) prevented hyperacute rejection, but the two grafts were rejected on days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II, the additional DFPP that was required to deplete the remaining 10% of anti-pig antibody was poorly tolerated and the two baboons died 4 h and 2 days, respectively, after renal transplantation. Although anti-pig IgM antibodies were reduced to 2% of pre-treatment level, IgM and C3 binding were detected in the graft as early as 1 h posttransplantation. These data suggest that the concentration of xeno-antigen epitopes expressed on pig organs may need to be reduced by genetic engineering to the much lower level of blood group A/B antigens on human kidneys if discordant xenotransplantation is to be successful.

ABO-Incompatible Kidney Transplantation with Donor-Specific Skin Graft

From November 3, 1975, to May 31, 1989, 711 (548 living-related and 163 cadavers) kidney transplantations were performed in our centers. In the final 2 years, 15 ABO-incompatible living related kidney transplantations were performed. In 4 cases, the recipient's blood groups was O and the donor's A1. In 3 cases the blood group of the recipient was A1 and the donor's AB, two patients were B with the donors A1 and the other 2 were O with donors B. The other 3 recipients group was B and the donors' were AB. The donors' and recipients' HLA-AB typing showed one haplotype matching in 12 and two haplotypes matching in 3 patients. The donors were mothers in 7 cases, sibling in 5, and father in 3 cases. At least 3 weeks before the renal transplantation, donor-specific skin grafts and subsequently splenectomy were performed on 9 recipients, but on 6 recipients without splenectomy. Following the skin graft, cross-match was done starting from the 15th day and then continued every week. The immunosuppression, which consisted of triple drugs (0.5 mg/kg prednisolone, 2 mg/kg cyclosporin-A and 2 mg/kg azathioprine) was followed by skin graft. Renal transplantation was performed according to cross-match and skin graft results, and all recipients prior to surgery received at least two sessions of plasmapheresis. Regular dose of immunosuppression that included triple drugs were used after the kidney transplantation and then Orthoclone OKT-3 and plasmapheresis were applied during the rejection episodes without bolus therapy. All patients were followed for 5 to 24 months (ave. 14,13 months).(ABSTRACT TRUNCATED AT 250 WORDS)