The New Deceased Donor Pancreas Allocation Schema: Do the Recommendations Go Far Enough?

This issue of Transplantation features a description of recent revisions in the algorithm for allocation of deceased donor pancreata to candidates for either vascularized whole-organ or islet transplants in the United States; the revisions were prompted by an analysis of pancreas usage and transplant outcomes under previous policies (1). The authors of that retrospective analysis are Mark Stegall and members of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) Kidney and Pancreas Transplant Committee. During the 3-year period from 2001 through 2003, the pancreas was not recovered in 11,880 donors, or 48% of the multiorgan donors available during this period. The reasons for the low recovery rate were multifactorial, but a cumbersome allocation process made it logistically difficult to place the pancreas that was not used locally, particularly for islet transplantation. The revised recommendations now divert pancreata from donors with a body mass index (BMI) >30 kg/m2 or age >50 years for preferential allocation to islet transplant candidates in the United States, provided such organs are offered first to, and not accepted by, solid organ pancreas transplant candidates at the local center. Questions remain: Does this revision go far enough? Are islet transplant candidates and the U.S. programs with which they are listed still unfairly disadvantaged when it comes to pancreas allocation for islet transplants (an issue one of us has previously discussed [2])? The debate is sensitive for several reasons. First, pancreas procurement and solid organ pancreas transplantation are reimbursed, whereas islet transplantation remains “investigational” in the United States. In Canada and in some centers in Europe, islet transplants are funded as “nonresearch” standard of care. In contrast, in the United States, islet allografts must be done under an investigational new device status under the jurisdiction of the Federal Drug Administration, and no charges may be transferred to the patient. Under these circumstances, insurance companies do not cover islet allografts. This situation will persist until such time as Biological Licensure is attained for islet allotransplantation. A move in this direction is currently underway, led by the National Institute of Diabetes and Digestive and Kidney Diseases in collaboration with Medicare, which will allow The Centers for Medicare & Medicaid Services division of the U.S. Department of Health and Human Services to reimburse for islet-after-kidney transplants in recipients entered into a clinical trial. Second, the high charge by organ procurement organizations (OPOs) for pancreata allocated to islet allograft candidates, relative to the funds available for clinical trials, impedes islet transplant advancement. A large proportion of the research money available must be used to reimburse the OPOs for the pancreata needed for islet isolation. The range of OPO charges for pancreas procurement varies considerably, from nominal up to the full rate used for solid organ transplants (averaging about $25,000). Why the procurement charge is so high under the current circumstances may be difficult for laypeople to grasp. Pancreas procurement for islet isolation is a straightforward, additional step in the multiorgan procurement process: it takes less than 30 min and needs little equipment (a couple of surgical staplers, sterile bags, and ice slush). Nonetheless, negotiating a reduction in charges can be difficult given the policy of most OPOs to amortize the overall costs of procurement across all organs. The business policies of most OPOs, unfortunately, do not account for the fact that the surgery required for removal of a pancreas for islet isolation is simpler than for solid organ transplantation (no need for predissection of the pancreatic vasculature), and thus takes less time. Thus, the actual costs of procurement are less when a pancreas will be used for islet transplantation and could be accompanied by a discount on charges, but the willingness to do so vary widely between OPOs. In fairness to the limited reform in the UNOS pancreas allocation policies outlined by Stegall and associates, there is no question that the metabolic outcomes in solid organ pancreas transplant recipients (3) are currently far more robust than in islet transplant recipients (4). An inexorable attrition of beta-cell function, with recurrence of insulin-dependence, has occurred between 3 and 5 years posttransplant in most islet allograft recipients (5). Although 70% retain at least some function, as manifested by persistent C-peptide secretion, normal or near-normal glycosylated hemoglobin levels and protection from hypoglycemic insulin reactions, only 10% remain free of the need for exogenous insulin (4, 5). By contrast, about 70% of whole-pancreas recipients remain insulin-independent at 3 to 5 years (3). Furthermore, most islet centers have required successful islet isolations from two, or occasionally more, pancreata in order to achieve initial insulin independence. Not every islet isolation is successful; in fact, the isolation process fails in 55% of attempts, meaning that a total of four donor pancreata may have been allocated to provide islets for a single recipient (5). In contrast, a carefully selected pancreas from a young, stable deceased donor transplanted as a solid organ will result in insulin independence in about 90% of the recipients, with good long-term function in the absence of rejection episodes (3). With both the old and the new allocation schemes for deceased donor pancreata, islet transplant candidates are considerably disadvantaged when it comes to accessing “Grade A” organs. The facts that islet isolation is inadequate in more than half the attempts and that two donors who give good yields are typically required for insulin-independence in the recipient to be achieved, is used to justify a biased allocation scheme. It seems likely (but is yet unproven) that the use of pancreata from stable deceased donors <50 years old would increase the incidence of successful islet isolations success rate, increase the early transplant success rate (insulin-independence) from single donors, and increase the long- term survival (durability) of islet allografts. In-depth analyses of these factors by the Collaborative Islet Transplant Registry will help to justify the plea for access to the most optimal organs for islet allografts (6). Although improving the access to pancreata from deceased donors >50 years old or with a BMI >30 is a step in the right direction, even the new policy fails to allow access of islet transplant candidates to the optimal donors and it is unlikely to improve islet allograft outcomes. A major issue previously was that deceased donor pancreata were being offered late in the process to islet transplant candidates. Because the pancreas must be offered first and turned down for solid organ transplantation, offers to islet candidates are likely to occur after aortic cross-clamping in the donor; sometimes an offer to an islet transplant candidate may not occur until after a pancreas has been shipped to, and then turned down by, a potential solid organ transplant candidate on “anatomical waivers.” The cold ischemic tolerance time of a pancreas is far lower for islet isolation than for solid organ transplantation; the isolation success rate declines sharply when the cold ischemic time exceeds 6 to 8 hr. The new schema may help to avoid postprocurement placement of pancreata from the >55-year-old, BMI >30 donors to islet transplant candidates, but the few optimal donor pancreata that will be allocated to islet candidates are still likely to be offered late and suffer from a deleterious period of cold ischemia. In our opinion, further refinement of pancreas allocation by UNOS is needed if the minimally invasive approach to beta-cell replacement—islet transplantation—is to reach its potential sooner rather than later. Development of islet transplantation could also be accelerated by reduction of the organ acquisition fee by OPOs for pancreata allocated to the candidates. Negotiations between islet transplant centers and OPOs of fees that allow increased pancreas utilization is key. If the organ acquisition fee for islet isolation had been be reduced to a reasonable $6,000 per pancreas, the OPOs could potentially have recouped more than $350 million if even half of the pancreata had been used from those 11,820 donors (2001 through 2003) whose pancreas was not procured (and thus wasted). A main reason for under use of pancreata for solid organ transplants is that the relatively few solitary pancreas transplant candidates listed have a short waiting time and the centers involved can be very particular in regard to the pancreas offers they accept. If pancreas and islet candidates were fully integrated into a common waiting list for organs that could be allocated to either from optimal donors, it is unlikely waiting times for solitary pancreas transplant candidates would be unduly lengthened. As long as offers are made before organ recovery, the process of allocating the pancreas to either a solid organ or islet transplant candidate would be straightforward. Stegall and colleagues refer to the variability in allocation practices among the OPOs, but do not discuss the details (1). Some OPOs give full priority to simultaneous pancreas-kidney (SPK) transplant candidates, and only in the situation where there is no SPK candidate are the kidneys then offered to kidney-alone candidates (2). Other OPOs give no special priority to SPK transplants, and thus a higher proportion of pancreata can be offered for solitary pancreas transplant candidates. We suggest that the simplest and best policy would be to have a single waiting list for both pancreas and islet transplant candidates. We believe that a single list will be most advantageous overall for beta cell replacement candidates and will further increase the relatively, and undesirably, low rates of pancreas procurement and use. Most likely the results of islet allografts will improve as more are done; the proportion of candidates listed for one or the other of the alternative methods of beta-cell replacement therapy will shift according to the outcomes and probability of success (2). The goal in beta cell replacement therapy for diabetes mellitus is to use the least invasive surgical technique—islet transplantation—in as many patients as possible, with the same rates of long-term insulin independence as with pancreas transplantation. Justifying expansion of islet transplant activity with a reciprocal decline in solid organ pancreas transplants will require improvements in long term islet recipient insulin-independence rates, but this goal is within reach as more efficient techniques for islet extraction are developed. We think that a common list of pancreas and islet transplant candidates would give the field of islet transplantation the flexibility to develop, without hampering the use of pancreata for solitary organ transplants, at least with the current number of candidates listed. If more candidates are added to the common list, thereby lengthening waiting times, the allocation policies could be revised, depending on differences in outcome. But right now, with short waiting times, such a differentiation is not justified. The tenets underlying our recommendation reflect the availability of organs for either pancreas or islet transplants, recognizing that at present only a highly restricted number of centers have the expertise to prepare islets for transplants.

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