On the Allocation of Cardiac Allografts from Blood Group-O Donors

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.     

Which ABO‐matching rule should be the decisive factor in the choice between a highly urgent and an elective patient?

ABO blood group matching policy between donor and recipient is a key element of organ allocation. Unequal distribution of the ABO blood groups in the population can lead to inequities in the distribution of organs to potential recipients. Furthermore, High Urgency liver transplant candidates might compromise the chances of transplantation for the elective patients. To compare the influence of the various ABO blood group matching policies on the transplantation rate of HU patients and on the subsequent donor liver availability for elective patients, a simulation study was undertaken. The study shows that in the Eurotransplant liver allocation program, a restricted ABO-compatible matching policy for HU liver patients offers the highest probability of acquiring a liver transplant, for both High Urgency- and elective patients, irrespective of their ABO blood group. A simulation study once again proved to be an elegant tool for objectively analysing various options in a complex organ allocation algorithm.     

Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts

Organ transplantation is the victim of his own success. The results of transplantation are excellent and more patients are activated on the waiting list. The need for organs exceeds the supply. Which criteria are used to allocate available grafts to patients on the waiting list ? Organ allocation and finding the "best match" between donor and recipients, is the goal of Eurotransplant, the organ sharing organization for seven European countries (Austria, Croatia, Germany, Luxemburg, Slovenia, The Netherlands and Belgium). Last decade, the allocation system has switched from a "center-driven" (organ allocated to a center) to a "patient-driven" system (organ allocated to a particular patient). For the allocation of abdominal organs some general allocation rules are followed: blood group compatibility, priority for high urgencies. The allocation of kidneys is based on a point score system based on waiting time, HLA and donor location (to reduce the cold ischemia time). In addition to this standard allocation procedure, there are still specific procedures for pediatric recipients and for candidates > or = 65 year old. There is also an "acceptable" mismatch program for recipients at high immunological risk. The liver allocation system recently changed and is now based on the MELD score, a formula that calculates the probability of death within 3 months on the waiting list. For pancreas and intestine, the system is based on blood group, medical urgency, waiting time, donor region and weight (for intestine).     

The heart-allocation simulation model: a tool for comparison of transplantation allocation policies

BACKGROUND: Numerous studies have investigated prognostic factors for the survival of transplant candidates waiting for a donor organ, but little is known about the impact of allocation policies on waiting list outcome. Simulation models would allow a comparison of different policies for allocating donor hearts on pretransplant outcome. METHODS: A model was built for the Eurotransplant waiting list for heart transplantation. Survival and delisting distributions were estimated from the Eurotransplant transplant candidate inflow between 1995 and 2000 (n=7,142). Other characteristics were obtained directly from the transplant candidate inflow of 1999 and 2000 (n=2,097) and the donor organs of 1998 and 1999 (n=1,520). Overall and subgroup waiting list mortality were estimated for allocation policies differing by ABO blood group, border, and clinical profile rules. RESULTS: The model estimated that international organ exchange reduces waiting list mortality in the different countries by 1.9% to 12.4%. An allocation policy incorporating the initial clinical profile of the transplant candidates further reduced waiting list mortality by 1.7%. Changing ABO rules toward identical matching yielded a slightly more equitable survival for the different groups, without an overall effect on mortality. The best possible allocation policy is the policy where organs are allocated to patients that are at highest risk of dying, and withholding organs from patients that would eventually delist because of improvement. CONCLUSIONS: Patients benefit from international organ exchange and by a heart allocation scheme based on clinical profiles. Timely delisting of patients who are-temporarily-too well for transplantation is the best waiting list policy.     

The “ABO Cross-transplantation Problem” in Liver Transplantation in Korea

ABO blood group matching policy between donor and recipients is a chief element of organ allocation. However, O blood group donors may donate to all other blood group recipients, and ABO cross-transplantation has led to excessively long delays for blood group O. To investigate the consequence of this problem, we analyzed the recipients/donor rates according to ABO blood groups and cross-transplantation rates among them. Data about deceased donors and liver transplants performed in Korea from January 2008 to September 2012 were reviewed. The proportion of recipient to donor in the O blood group was lower compared to non-O groups (0.61). The percentage of O blood group transplantations in the Korean Network for Organ Sharing (KONOS) status 2B was lower than non-O groups (13.6%). In the status 1 and 2A groups, 44.4% of O blood group donors were allocated to non-O transplantations. Also, 30.7% O blood group donors were allocated to non-O transplantations in the status 2B groups. In conclusion, the ABO cross-transplantation in blood group O donors has led to lower transplantation rates of blood group O in status 1, 2A, and especially, the 2B group. Therefore, the KONOS allocation system should be re-evaluated to address this problem.     

Distribution of ABO Blood Group Antibody Titers in Pediatric Patients Awaiting Renal Transplantation: Implications for Organ Allocation Policy

BACKGROUND: Blood group-incompatible transplantation is one strategy used when a potential recipient does not have a compatible living donor. Current practice includes desensitization strategies to reduce antibody titers. However, when antibodies are low, in cardiac transplantation in neonates for example, no desensitization is required. This study is the first to examine the distribution of ABO blood group antibody titers in a population of pediatric patients on the deceased-donor renal transplantation waiting list. METHODS: All patients from two pediatric nephrology centers active on the national deceased-donor waiting list had antibody titers (total immunoglobulin load) measured. A simulation modeling the effect of allocating blood group-incompatible deceased-donor kidneys to those patients with titers of 16 or lower was developed. RESULTS: Twenty-four children were screened; eight (33.3%) had titers of either anti-A or anti-B antibodies of 8 or lower. A further three (12.5%) had either an anti-A or anti-B antibody titer of 16. Blood group A or B patients had lower antibody levels than blood group O patients. In blood group O patients, levels of anti-A antibodies were higher than anti-B antibodies (Wilcoxon signed rank test, P=0.028). The simulation model showed that a change in organ allocation policy would increase pediatric transplant activity by 2.2% and reduce the median waiting time for a transplant. CONCLUSION: This allocation strategy may be of particular benefit to those pediatric patients who have been on the deceased-donor waiting list for a long time or those with a high calculated reaction frequency.     

Persistently low transplantation rate of ABO blood type O and highly sensitised patients despite alternative transplantation programs

ABO blood type O and highly sensitised patients have the smallest chance to receive kidney transplantation. Do alternative donation programs increase this chance? In the period studied: 2323 patients were enlisted on the Rotterdam waiting list for a renal transplantation: 435 patients still waiting (WL), 464 delisted without transplantation (DWT). 1424 received deceased donor (DD, 535) or living donor (LD, 889, including 204 alternative) transplantation. Alternative LD programs in our centre are: paired kidney‐exchange, altruistic with domino‐paired donation and ABO‐incompatible donation (ABOi). Compared to populations not transplanted, blood type O recipients are significantly underrepresented in DD and all LD transplantation populations, except the ABOi program. Highly sensitised patients are overrepresented in DD, but underrepresented in all LD transplantation populations. The high transplantation rate of highly sensitised patients was the result of Eurotransplant Acceptable mismatch program (AM). The LD ABOi and DD AM programs are the only alternative donation programs favourable for patients with low chances. While the contribution of direct LD transplantations will increase in time, the relative success rate of low‐chance patients will decrease. Beside increasing LD ABOi transplantation, a new DD allocation model favouring both highly immunised and blood type O patients is essential.     

Increased Access to Transplantation for Blood Group B Cadaveric Waiting List Candidates by Using A2 Kidneys: Time for a New National System?

Since blood group B end-stage renal disease (ESRD) patients have less access to donor kidneys and a higher minority composition than any other blood group, the United Network for Organ Sharing (UNOS) approved a voluntary national kidney allocation variance to allow organ procurement organizations (OPOs) to preferentially allocate A2 and A2B kidneys to B candidates. The Midwest Transplant Network OPO has preferentially allocated and transplanted kidneys from blood group A2 and A2B donors to our blood group B waiting list candidates for more than 7 years to increase access to kidneys for the B candidates on our OPO-wide waiting list. Between 1994 and 2000, a total of 121 blood group B ESRD patients from our OPO-wide cadaveric kidney waiting list were transplanted. Thirty-four per cent (41/121) of those B candidates received either an A2 or an A2B kidney. One- and 5-year graft survival rates for the group of B recipients of A2 or A2B kidneys were 91 and 85% (died with functioning graft [DWFG] censored), respectively, which were not significantly different from those of 91 and 80% for the 80 B recipients of B or O kidneys (Wilcoxon = 0.48; log-rank = 0.55). These data support the national trial for additional OPOs to voluntarily allocate A2 and A2B kidneys preferentially to B waiting list candidates, thus increasing access of blood group B patients to renal transplantation.     

Thoracic organ transplantation in the United States, 1994–2003

Using OPTN/SRTR data, this article reviews the state of thoracic organ transplantation in 2003 and the previous decade. Time spent on the heart waiting list has increased significantly over the last decade. The percentage of patients awaiting heart transplantation for >2 years increased from 23% in 1994 to 49% by 2003. However, there has been a general decline in heart waiting list death rates over the decade. In 2003, the lung transplant waiting list reached a record high of 3,836 registrants, up slightly from 2002 and more than threefold since 1994. One-year patient survival for those receiving lungs in 2002 was 82%, a statistically significant improvement from 2001 (78%). The number of patients awaiting a heart-lung transplant, declining since 1998, reached 189 in 2003. Adjusted patient survival for heart-lung recipients is consistently worse than the corresponding rate for isolated lung recipients, primarily due to worse outcomes for heart-lung recipients with congenital heart disease. A new lung allocation system, approved in June 2004, derives from the survival benefit of transplantation with consideration of urgency based on waiting list survival, instead of being based solely on waiting time. A goal of the policy is to minimize deaths on the waiting list.     

Liver transplantation in Germany

As in other western countries the major challenge of liver transplantation in Germany is to expand the number of liver transplantations in respect to the increasing disparity of qualified patients on the waiting list and the still static availability of brain death donor organs. The problem of death on the waiting list has become overt since the German transplantation law has been installed, which has changed the former center-oriented to a patient-oriented allocation weighting waiting time over medical urgency criteria. The more liberal acceptance of so called marginal cadaveric donor livers will probably impair further improvements in the acute and long-term outcome of liver transplantation. This problem can be partially compensated by the use of novel surgical techniques, such as splitting a donor liver to be transplanted into two adult recipients or, more commonly and safe, into an adult and one child. Another alternative to increase the donor pool is living donor liver transplantation, which was first introduced for pediatric recipients but is now increasingly used in adults. In 2001, a constant number of 757 liver transplantations were performed in Germany, including 12.5 % living donor transplantations. Recently, general guidelines for the selection of patients with end-stage liver disease and acute liver failure have been published by the Bundes?rztekammer. Additional developments have contributed to improve the results of liver replacement including individualized immunosuppression strategies and novel treatment options to avoid recurrent viral disease following transplantation.     

Model for End-Stage Liver Disease: Impact of the New Deceased Donor Liver Allocation Policy in São Paulo, Brazil

Since 1997, organ transplantation in Brazil has been regulated by a federal law, which was created to guarantee equal access to treatment on a national scale. Centralized deceased donor organ procurement and sharing are controlled by the Health Department of each state of the nation, following a regional allocation policy. In São Paulo, time on the waiting list was the main criterion adopted to allocate deceased donor livers up to July 15, 2006. After that, model for end-stage liver disease/pediatric end-stage liver disease (MELD/PELD) scores were the main criteria. The aim of this study was to investigate the impact of the new criteria on patient survival rates using 895 consecutive liver recipients. The 1-year patient survival rates were compared between recipients transplanted based on the waiting time policy and based on MELD/PELD scores showing similar results (69.79% vs 66.69%; P = NS). Regarding liver allocation based on MELD/PELD scores, worse survival outcomes were observed among recipients transplanted with higher MELD scores. Also, under the new criteria, a high frequency of hepatocellular carcinoma and pediatric recipients underwent transplantation.     

Potential Effect of Using ABO-Compatible Living-Donor Liver Transplantation

Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.     

Successful Organ Transplantation from Donors Poisoned with a Carbamate Insecticide

Currently, liver transplantation is the only option for patients with end‐stage liver disease. In Brazil, the mortality rate on the waiting list is about 25%. Multiple strategies to expand the donor pool are being pursed, however, grafts from poisoned donors are rarely used. This report documents successful liver, kidney and heart transplantations from four female donors who suffered brain death by hypoxia despite cardiopulmonary resuscitation following Aldicarb exposure ([2‐methyl‐2‐(methylthio)propionaldehyde O‐(methylcarbamoyl)‐oxime]). The success rate of 12 grafts from four donors poisoned by Aldicarb was 91% 6 months after transplantation. Poisoned patients are another pool of organ donors who at present are probably underused by transplantation services. More studies are necessary to confirm the safety for the recipients.     

Extended Criteria Donors in Liver Transplantation: Adapting Donor Quality and Recipient

Despite the progressive increase in the number of liver transplantations, the mortality on the waiting list remains between 5% and 10%, and patients have to deal with longer waiting periods. Facing this situation, transplant centers have developed alternatives to increase the number of grafts by accepting donors who were previously considered to be inadequate, because they are at higher risk of initial poor function and graft failure or may cause disease transmission. Currently, some marginal donors are being routinely used: elderly donors, steatotic grafts, non-heart-beating donors, hepatitis C virus-positive (HCV+) or hepatitis B core antibody-positive donors. These so-called marginal or extended-criteria donors were initially used in high-risk or urgent recipients; however, the number of marginal grafts has significantly increased, forcing the transplant community toward their more rationale use to maintain excellent results of liver transplantation. In this new scenario, the adequacy between donor and recipient may be paramount. Advanced donor age seems to be related to a greater graft failure rate in HCV+ recipients. Early survival seems to be significantly reduced when steatotic grafts are used in recipients with high Model for End-stage Liver Disease (MELD) scores. Moreover, a decreased survival has been observed among high-risk patients receiving organs from marginal donors. No benefit seems to exist when high-donor risk index grafts are transplanted into recipients with low MELD Scores. The recognition of various donor groups according to their quality and the need for good donor and recipient selection must lead us to define new policies for organ allocation of marginal grafts that may come into conflict with current policies of organ allocation according to the risk of death among patients awaiting a liver transplantation.     

Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient‐years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO‐identical and 23 (6.1%) ABO‐compatible. The 5‐year cumulative incidence of death was 11.2% (SE 1.4%), and of transplantation 72.5% (SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation.     

Hemolytic anemia after ABO nonidentical living donor kidney transplantation

Introduction  ABO compatible non-identical kidney transplants are used frequently. Acquired hemolytic anemia has been reported after ABO mismatched transplantation. Patients of A, B or AB blood groups may receive organs from ABO-compatible, but non-identical donors, mostly from O blood group donors. It may also occur in patients of the AB blood group who receive a kidney from a donor of the A or B blood groups. Patients and methods  ABO non-identical living donor kidney transplantation was done in 214 cases. All studied patients received kidneys from one haplotype HLA mismatched living donors and had pretransplant non-specific blood transfusions. There were 164 males and 50 females with a mean age of 30 years. Ten patients with cyclosporine (CsA)-based therapy developed hemolysis. CsA was stopped in patients maintained on triple immunosuppression (pred, CsA, AZA) and shifted to azathioprine in patients maintained on pred CsA therapy. In all patients pretransplant antibody screen, direct antiglobulin test (DAT) and cytotoxic cross match were all negative. Results  The prognosis was excellent in nine patients, and one died from severe hemolysis. Hemolytic anemia was more frequent among blood group A recipients (60% of our cases) and more severe among recipient blood group B. Six patients received antigen-negative packed RBCs. Univariate analysis demonstrated significant impact for recipient age, donor sex, number of pretransplant blood transfusions, primary immunosuppression, time to onset of diuresis, recipient and donor blood groups. Multivariate analysis restricted the significance to blood group of donor and recipient, time to onset of diuresis and primary immunosuppression. Conclusions  Post transplant hemolysis is infrequent after renal transplantation; however, it may occur with compatible, non-identical ABO blood group donors. Blood group of donor and recipient, time to onset of diuresis and primary immunosuppression (mainly CsA) were significant risk factors in hemolytic anemia in patients after ABO non-identical living donor kidney transplantation. The condition is usually mild and self limited, and change of immunosuppression (stop CsA) can treat the condition.     

Renal transplantation across the ABO barrier using A2 kidneys.

BACKGROUND: The waiting list for cadaveric kidney transplantation has continued to grow, and with the relative scarcity of cadaver donors, the median waiting time for patients in the United States increased to 824 days in 1994. The median waiting times for patients with blood groups B or O were 1329 and 1007 days, respectively. Allocation of blood group A2 kidneys (20% of group A) to blood group O and B patients expands their potential donor pool and shortens their waiting time for a kidney transplantation. METHODS: Between May 1991 and June 1998, we transplanted 15 A2 kidneys into 6 blood group O and 9 blood group B patients. Anti-A isoagglutinins were measured before transplantation, and patients with anti-A1 titers > or = 1:8 underwent plasmapheresis (PP). RESULTS: One patient with high titer anti-A antibodies, who did not receive PP, lost her allograft because of hyperacute rejection. Allograft function was excellent in the remaining 14 patients, with a mean serum creatinine level of 1.7 (+/-0.89) mg/dl at 1 month and 1.3 (+/-0.34) mg/dl at 1 year. The actuarial 1-year graft survival rate was 93.3+/-6.4% and the patient survival rate was 100%. CONCLUSION: We conclude that the allocation of blood group A2 kidneys for blood group O and B recipients is a practical way to expand the donor pool for these transplant candidates. PP may be important for reducing the levels of anti-A1 and anti-A2 antibodies and for reducing the risk of hyperacute rejection. Splenectomy seems to be unnecessary.     

ABO blood group-related waiting list disparities in liver transplant candidates: effect of the MELD adoption

BACKGROUND: Blood group O candidates remain on the waiting list for a liver transplant for a longer time than candidates of other blood groups. Herein, we analyzed potential factors affecting waiting times in the period that preceded the introduction of the model for end-stage liver disease (MELD) and in MELD era, remarking possible corrections introduced by the adoption of the MELD. METHODS: Our analysis was entirely based on data obtained from the "Organ Procurement and Transplantation Network", referring to the periods before and after the adoption of the MELD. RESULTS: In the MELD era, taking into consideration all candidates, the cumulative probability of remaining on the waiting list significantly diminished whereas that of undergoing transplantation significantly increased when compared with the pre-MELD era. However, group O candidates maintained the lowest cumulative probability of undergoing liver transplant, in all MELD classes, and the highest percentage of list removal for death/too sick. What caused the highest disadvantage for group O, in both eras, was the use of group O organs for ABO-compatible transplants, even in the absence of urgency. In candidates receiving ABO-compatible organs a significantly lower graft survival rate was observed compared with candidates receiving ABO-identical organs, even when the analysis was adjusted for the MELD score. CONCLUSIONS: The introduction of the MELD significantly reduced the waiting time for all candidates as also the shift of group O organs. Limiting ABO-compatible organs exclusively to urgent cases would have a positive effect not only in terms of individual justice, but also terms of in general utility, considering the effect of ABO-matching on graft survival.     

Current experience with renal transplantation across the ABO barrier.

Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS)