Multiple-Organ Transplantation from a Single Donor

In the first 4 months of 2011, 9,055 organ transplantations were performed in the United States.¹ At that rate, more than 27,000 organs would be transplanted this year alone. However, this number still falls terribly short of the need for transplantable organs in the United States. As of July 2011, 111,946 candidates remained on waiting lists for transplantation. According to the Organ Procurement & Transplantation Network (OPTN) data from 2003–2004 (the most recent data available), the median waiting time for Status 1A hearts is 50 days, and the waiting time for other organs, notably kidneys and livers, is much longer.¹ In addition, waiting times have increased significantly over the past 15 years.² The demand for organs has increased as transplantation has become more accepted in society and has proved to be an effective treatment in combating organ failure; however, the supply of organs has been unable to keep up.

Multiple-organ transplantation is a rare event; very few programs in the U.S. and around the world offer multiple-organ transplants (Table I). Previously, survival numbers served as argument against such surgical interventions. However, the current mid- and long-term outcomes of multiple-organ transplantation are comparable to those of single-organ transplantation, and evidence increasingly indicates that recipients of multiple organs from the same donor have a lower rate of organ rejection and chronic organ dysfunction. Nonetheless, the predominant notion is that donor organs are such a scarce resource that as many patients as possible should be served and, therefore, transplanting multiple organs into 1 recipient should be discouraged. The United Network for Organ Sharing (UNOS) has made it clear in its rules that patients who are awaiting multiple-organ transplantation should be preferred over patients who are awaiting a single organ, provided that the single-organ candidate with the highest urgency does not qualify for the organ (OPTN policies 3.7.7 and 3.9.3).

TABLE I. United Network for Organ Sharing Multiple-Organ Transplantation Volume in 2008 and 2009

In reality, organs are allocated by running the list for each individual organ first. If a suitable recipient is found, the organ is offered to that person. If the organ is accepted by the transplant center for an individual, it cannot be allocated to the multiple-organ candidate who is lower on the waiting list. For example, a patient who needs a heart-lung transplant can be offered the lungs after the heart has already been assigned to another patient.

This practice of organ allocation has led to a serious disadvantage for multiple-organ recipients. In the state of Texas, the mortality rate for patients who are on the waiting list for a heart-lung transplant is more than twice as high as for patients who are listed for heart or lungs only. This means that the suitability of combined heart-lung transplant in adults is driven solely by the high rate of mortality for patients who are waiting for this operation, even though heart-lung transplantation outcomes are equal or superior to those of isolated heart or lung transplants.

The current policies of organ allocation need to be revised to provide equal opportunity to patients who are waiting for multiple organs. These patients are already at a disadvantage, because it is extremely difficult to find multiple organs of good quality in the same donor and because size constraints further limit the chances of finding suitable multiple-organ donors. The allocation system should not further reduce their chances; UNOS should mandate that the list with multiple-organ candidates be checked first. Some exceptions for very sick single-organ recipients may be implemented, to avoid hardship.

Proposed criteria for the allocation of donor organs to potential recipients have included age, medical benefit, merit, ability to pay, and geographic residence, among others.³ Although factors such as age, merit, and ability to pay have been discarded, medical benefit, and, to a lesser extent, a patient's geographic residence have become standard determining factors in the allocation of organs in many transplant programs throughout the U.S. Currently, the Council on Ethical and Judicial Affairs (CEJA) outlines acceptable criteria relating to medical need for the allocation of transplantable organs and other scarce medical resources as follows: 1) the likelihood of benefit to the patient; 2) the impact of treatment in improving the quality of the patient's life; 3) the duration of benefit; 4) the urgency of the patient's condition; and, in some cases, 5) the amount of resources required for successful treatment of the patient.⁴ In essence, the CEJA asks whether the patient will benefit substantially from an organ transplant. This benefit may manifest itself as improved quality of life (compared with current condition) and extended length of life, among others. While the CEJA allows that it may occasionally be appropriate “to treat patients who will need less of a scarce resource rather than patients expected to need more,”⁴ it makes it very clear that resources should not be conserved by denying existing patients access to treatment in the expectation that a hypothetical patient may need those resources. In addition, the CEJA states that criterion 5 should be evaluated only if criteria 1 through 4 are equal. For patients who need multiple-organs, the same holds true, because the scarcity of organs may be used only as a factor when “potential transplant recipients cannot be distinguished on the basis of medical need or suitability.”⁴

In most Western countries (the U.S. included), organ-allocation policies hinge on balancing the values of justice and utility.⁵ For this purpose, justice is defined as patients' having an equal opportunity to receive a scarce resource (all recipients must spend their share of time on a transplant waiting list), except in cases when “resources are allocated in light of morally relevant differences, such as those pertaining to need or likely benefit.”^6,7 Even then, these morally relevant differences may be used only when there are “very substantial differences in such factors as probable success.”⁸ On the other hand, the utilitarian mindset toward organ allocation emphasizes the “optimal use of resources, so that the greatest total benefit is obtained.”⁹ By the utilitarian principle, overall patient outcomes supersede the necessity of giving every patient an opportunity to compete for organ transplantation, given the scarcity of resources. Recent trends in organ-allocation policy have emphasized overall patient outcomes over the relative objectivity of comparing waiting times to determine who receives the organs.⁷ However, these trends have run contrary to popular opinion, with survey results showing that the public places a more substantial value on ensuring that all transplant candidates have equal access to organs (justice), even if this results in a marked decrease in the chance that the organs will save the maximum number of lives (utility).¹⁰ It is troubling that the current trend in organ-allocation policy differs so greatly from popular opinion; this difference perhaps indicates that further review of the process by which organs are allocated (especially multiple organs) is overdue.

The transplantation of multiple organs into a single patient is relatively rare: only 583 such operations were performed in 2008. Despite the low rates of multiple-organ transplantation, many studies^11–15 have revealed that this is no more dangerous than single-organ transplantation (from a survival-rate perspective). Indeed, in many of the same studies, multiple-organ transplantation has even been linked with lower rates of acute and chronic rejection postoperatively, because recipients received a protective effect. (This protection is an immune modulation hypothesized to be a result of increased introduction of donor hematopoietic elements carried into the organ recipient within the tissue mass of multiple organs.¹¹) More specifically, in 1 study, transplantation of multiple organs from the same donor was found to confer protection from both acute and chronic cardiac rejection, regardless of whether the additional transplanted organ was a kidney or a lung.¹¹ Equal survival rates between multiple-organ recipients and single-organ recipients are in direct opposition to the CEJA's contention that “patients needing multiple transplants usually face a lower likelihood of benefit than other equally suitable organ recipients [patients only needing a single organ].”⁴ The organ-allocation process has been shifting toward a more utilitarian viewpoint; however, the aforementioned recent studies have indicated the viability and success of performing multiple-organ transplantation, which suggests possible design flaws in allocation policies that give lower priority to patients who need multiple organs.

Given the increased acceptance of multiple-organ transplantation, it must be noted that the studies mentioned above have found that the protective effect is present only in recipients whose organs came from a single donor. No publications have shown that the same protective effect exists in recipients of organs from multiple donors. This fact, in addition to the logistical nightmare of arranging a concurrent transplantation procedure using organs from separate donors and the various complications that would result from sequential transplantation procedures, lends support to the notion that multiple-organ transplant recipients should receive their organs from the same donor. This position is also supported by the OPTN policies for organ allocation. Regulation 3.9.3 states: “When the candidate is eligible to receive a heart, lung, or liver pursuant to Policies 3.6 (Allocation of Livers) and 3.7 (Allocation of Thoracic Organs) or an approved variant of these policies, the second required organ shall be allocated to the multiple-organ candidate from the same donor if the donor is located in the same local organ distribution unit where the multiple-organ candidate is registered. If the multiple-organ candidate is on a waiting list outside the local organ distribution unit where the donor is located, voluntary sharing of the second organ is recommended.”¹⁶

Multiple-organ transplantation can be successful if donor and recipient reside in the same organ distribution unit; however, too many opportunities for multiple-organ transplantation have been missed due to a lack of communication between organ distribution units and actions that were not in the spirit of OPTN policy 3.9.3, which recommends voluntary sharing of the second organ. As discussed above, organ-allocation policy should be firmly rooted in medical benefit to the patient, not in relations between organ distribution units; allocation limitations should be medical (for example, organ ischemic times). In addition, OPTN policy 3.7.7 states: “When the candidate is eligible to receive a heart in accordance with Policy 3.7, or an approved variant of this policy, the lung shall be allocated to the heart-lung candidate from the same donor. When the candidate is eligible to receive a lung in accordance with Policy 3.7, or an approved variant of this policy, the heart shall be allocated to the heart-lung candidate from the same donor if no suitable Status 1A isolated heart candidates are eligible to receive the heart.”¹⁷ This regulation adds support to the argument for multiple-organ transplantation from a single donor. While certain inconsistencies remain (for example, lungs from the same donor can be allocated, unscreened, to heart-eligible candidates, whereas hearts must first pass through a Status 1A heart screening before they can be allocated to lung-eligible candidates), widespread implementation of OPTN policies 3.7.7 and 3.9.3 would provide a significant boost to multiple-organ transplants from a single donor.

In summary, popular opinion favors multiple-organ transplantation (as seen by the public's preference of justice over utility in the design of organ-allocation programs¹⁰). In addition, multiple studies have shown that multiple-organ transplantation from a single donor is not only safe and effective but also seems to imbue upon recipients a protective effect against acute and chronic rejection.¹¹ Moreover, OPTN policies are favorable to multiple-organ transplantation from a single donor. Therefore, multiple-organ transplantation from a single donor should be encouraged in transplant programs throughout the United States. Furthermore, the current organ-allocation practices should be reevaluated as changes in policy are put into wider effect.