FACE + HAND TRANSPLANTS : NEW NAME, NEW REGULATORY NICHE

Clinical transplantation has moved forward in leaps and bounds, surpassing the speed of the U.S.  government in addressing regulatory standards for new transplant types. This is neither an irrelevant nor a minor issue and has just been definitively addressed by the Final Rule published in the July 3, 2013 Federal Register. The National Organ Transplant Act (NOTA) originally enacted in 1984 had defined a specific list of transplant organs based on all of the transplant types that were performed in that era. The Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) oversee and regulate those types of organ transplantation with a fully developed set of bylaws for member institutions and policies that determine how transplants are undertaken. These transplants currently include:

ORGAN TRANSPLANTS

Kidney
Liver
Heart
Lung
Pancreas
Intestine (any part of the intestinal tract)

In contrast, human cells or tissue for transplantation are under the regulatory jurisdiction of the Food and Drug Administration (FDA) under Section 361 of the Public Health Service Act and 21 CFR parts 1270 and 1271.  Examples (not inclusive) of Cell and Tissue "Implants/Transplants" include:

CELL + TISSUE "IMPLANTS/TRANSPLANTS" 

Bone

Skin

Cornea

Ligaments

Stem cells

Peripheral blood

Cord blood

Oocytes

Semen

Face, hand, larynx, and abdominal wall transplants are all examples of transplants that did not clearly fit into either of the two pre-existing categories. Agreeing with advocates within the transplant community, the Secretary of Health and Human Services issued this Final Rule that has formally created a new category of Vascularized Composite Allografts (VCA), (allograft = transplant between non-identical members of the same species) that is defined based on functions below (ischemia is a period of interrupted blood, see below):

VASCULARIZED COMPOSITE ALLOGRAFTS 

1. Vascularized - requires blood flow by surgical connection
2. Contains multiple tissue types
3. Recovered from a human donor as an anatomical/structural unit
4. Transplanted into a human recipient as an anatomical/structural unit
5. Minimally manipulated or processed (but may be cut or shaped)
6. For homologous use (i.e., to be used for the same purpose in the recipient as it was in the donor)
7. Subject to ischemia and therefore stored only temporarily
8. Subject to allograft rejection and generally requiring immunosuppression

The Final Rule also clearly stipulates that VCA transplants fall under the jurisdiction of the OPTN/UNOS, not the FDA. Major implications of this definition are that VCA transplants may only be performed at OPTN member institutions in good standing. New policies specifically applicable to VCA transplants clearly need to be developed by the OPTN/UNOS.

Because of the unique issues pertaining to donor consent for these specific transplant types, wherein donor identification may be retained (e.g., fingerprints and facial identifiers), the Final Rule implies that donor specific consent should be undertaken on a case-by-case basis. This is the current ad hoc practice. But new issues of allocation will arise if the number of transplants begins to grow substantially. For example, there is no other transplant type in which skin color may be relevant!

Overall, a new field of medicine is currently developing at a very rapid pace. This one step is an important one. It will be challenging and exciting as others are made. Stay tuned.

KIDNEY TRIAGE BECOMING MORE SEVERE

Acknowledging reality, the Board of Directors of the United Network for Organ Sharing (UNOS)  accepted recommended changes to the allocation policy for deceased donor kidneys throughout the U.S. at its meeting on June 24-25, 2013. This policy determines how a specific kidney is offered to a specific waiting patient by defining how the UNOS computer generates the specific list in response to availability of a donor.  In the context of the extraordinary discrepancy between people waiting and the number of organs available, several fundamental problems are intended to be improved with the amended policy (see below).

A key change involves implementation of the Kidney Donor Profile Index (KDPI) as a measure of the risk of kidney failure after transplantation, with 100% being the worst and 1% the best possible values. An organ with a KDPI of 20% is more likely to function than 80% of transplanted kidneys - pretty darned good. Since one would not like to transplant an organ that is likely to fail, the KDPI is used as a direct measure of donor kidney quality.

Waiting candidates are stratified into 4 groups based on the KDPI and a second formula, the estimated post-transplant survival (EPTS).  This not-so-subtle means of including the candidate's statistical life expectancy following transplantation is a major step in the allocation scheme, taken in order to maximize the number of life years for the kidney following transplantation (LYFT).  It is based on the candidate age, length of time on dialysis, prior transplantation and presence of diabetes. However, the new policy amendment will incorporate the EPTS to advantage just those 20% of candidates with the best likely survival.

Now, combining the KDPI and EPTS will lead to the 20% of best KDPI organs being matched to pediatric patients and adult patients with the best EPTS. Pediatric patients are still given an advantage for organs with a KDPI up to 35%. Between KDPI of 35-85% adult recipients are addressed by the standard allocation factors already in effect. Above 85% broad sharing (beyond local areas) will be undertaken promptly in order to avoid discarding potentially transplantable organs. 

These changes have been neither reactive nor rapid, but have followed years of debate and formal procedure that included opportunities for input from all stakeholders. Nonetheless, the starkness of  including some healthier candidates while excluding sicker ones from access to the best kidneys, is not lost on anyone involved. This "cherry-picking" of transplant candidates is a deeply distasteful but necessary response to the lack of sufficient resources. Please take a moment to register your opinion about these changes by answering the poll at the bottom right of this webpage - thanks.

NO GUARANTEE WITH THIS ORGAN

Any donated human organ or tissue may harbor an unwanted, undiscovered or unrecognized infection, malignancy or other disease. With the transplant, irregardless of the best intentions and most up to date testing, that disease is donated too and may cause serious illness(even death) in a recipient. To minimize this risk, to allow assessment of the risk, and to facilitate informed judgement about whether or not to proceed......in advance of the transplant..... are the objectives. But risk cannot be completely eliminated.

The U.S. Centers for Disease Control and Prevention (CDC) has just issued long awaited guidelines for use in preventing the transmission of Hepatitis B (hep B),  Hepatitis C (hep C) and HIV through organ transplantation. They are based on currently available evidence and expert opinions, and formally update guidelines last published in 1994. An essential difference between organ donation and blood or tissue donation led to the restriction of these new guidelines only to the former field. In organ donation transplantation must proceed within hours of the procurement of the donated material that might bear infection. In contrast, both blood and tissue are typically recovered, processed and stored for a longer period of time varying from multiple days to even months or longer. During that interval definitive testing and further risk reduction can clearly be performed.

This rapid time frame within which results of any laboratory testing must be available so that organ procurement and transplantation are not unduly delayed defines different ground rules than in most medical scenarios. For example, only a few labs throughout the country perform the most specialized testing (nucleic acid testing -NAT) for Hep B, Hep C and HIV with 24/7/365 availability and rapid turn around. Blood samples are typically sent by courier to one of these labs when testing of a deceased donor is required. Of course, these steps do increase the cost of transplantation.

A practical approach was, by necessity, taken by the U.S. Public Health Service in developing the guidelines. For example, if one of the test results indicates the presence of  Hep B, Hep C or HIV when the virus is really not present (a false positive result), the inappropriate exclusion of the organ donor would be a serious consequence costing one or more lives. The need to balance the potential benefit to be gained from a successful transplant, with the statistical risk of using the possibly infected organ is acknowledged in the guidelines. Thus, it might be reasonable to use a liver from a donor who is suspected of having a false positive test if the liver candidate is at death's door and no other organs are available. But, it would not be reasonable to use the same donor's tissue without clarification of the possible infection.

Wisely, these guidelines also delve deeply into the important issue of involving the patient or family (if the patient is unable) through education when transplantation is only a concept, and through full informed consent when the detailed risks and benefits are known. This is a codification of the timing and content of informed consent similar to other approaches in this tightly regulated field.

Behavioral factors that increase the donor's risk of infection with Hep B, Hep C or HIV include sex with an infected person in the preceding 12 months, male-male sex within the preceding 12 months, people who have had sex with a person in exchange for money or drugs in the preceding 12 months, people who have had sex with a person who injected drugs in the preceding 12 months, a child < 18 months born to an infected or at risk mother, a child who has been breastfed within the preceding 12 months by an infected or at risk mother, people who injected drugs in the preceding 12 months, people in lockup, jail, prison or a juvenile correctional facility > 72 hours in the preceding 12 months, and people newly diagnosed with a sexually transmitted disease in the preceding 12 months.

For any transplant that involved an increased risk of transmission of Hep B, Hep C or HIV, surveillance testing of the recipient for the first year is recommended. If infection does occur, treatment can be initiated as early as possible with the intent of staving off serious illness. 

Today, these are the most common severe viral infections that concern transplant recipients. But previously, similar donor transmitted infection with the cytomegalovirus (CMV) and the Epstein Barr virus (EBV) were also highly problematic, at times even causing fatalities. Now these infections are much more manageable because of the anti-viral medications available for use.

If all of these details seem frightening, the real statistic that new (de novo) Hep B, Hep C or HIV infection through transplantation is very rare should be reassuring. The newly available document has simply formalized screening practices that have already become routine at many transplant programs for the protection of patients. Patients are entitled to be familiar with any unusual risks posed by the specific donor whose organ they are being offered (if they are so fortunate). Patients should feel empowered to ask about unusual issues with their donor (if they have not already been informed, which should happen). 

Remember that the only way to have no risk at all is to have no transplant. If a transplant does happen, the human donor's organ has been assessed with a risk/benefit ratio tailored to the specific recipient who should have been informed and should have intentionally opted to proceed. Of course, the transplant team would not typically offer an organ that they did not consider acceptable for that patient. But, in the end, it must be the patient (and/or the family) who agrees to go ahead.

HOPE - A LEGISLATIVE ACT NEEDED IN TRANSPLANTATION

U.S. federal law currently prohibits the transplantation of organs from HIV positive donors - a hold over from an early stage in the HIV era. But today many believe that cautious exploration of the safety of using HIV +ve donor organs for HIV +ve recipients may be a reasonable strategy to expansion of the critically limited organ donor pool. Similar approachs are used (with informed consent from the recipients) for patients and donors infected with the hepatitis B and C viruses, with favorable outcomes.  There was therefore substantial cause for preliminary celebration on June 17, 2013 when the U.S. Senate unanimously approved the HIV Organ Policy Act (HOPE Act; S. 330).

This legislation directs the Department of Health and Human Services (DHHS) and the Organ Procurement and Transplantation Network (OPTN) to develop and institute standards for the use of HIV positive organs in HIV positive recipients if ongoing research warrants. The Secretary of DHHS is also directed to : (1) review annually the results of scientific research in conjunction with the Network to determine whether they warrant revision of quality standards relating to donated HIV-infected organs and to the safety of cross-strain transplantation; and the Network, if the review so warrants, is directed to revise its standards in a way that ensures the changes will not reduce the safety of organ transplantation.

This legislation has been referred back to the House of Representatives and is now in the House Committee on 1) the Judiciary and 2) Energy and Commerce.  It was initially introduced by Representative Lois Capps (California) as H.R. 698 and now has 30 co-sponsors. Why not check to see whether your Representative has yet joined as a co-sponsor? If not, call or e-mail his/her office or website to indicate your support. This bill does have bipartisan and bicameral (both houses of Congress) support. Let's help stimulate our politicians to take a logical step forward to solve the organ shortage, even if it is a small one. Every bit helps.