Solid Organ Transplant

Published on 09/04/2015 by admin

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42 Solid Organ Transplant

Providing palliative care to patients pursuing an intensive, life-extending treatment such as organ transplantation may seem paradoxical. However, the presence of severe underlying disease, inadequate organ availability, and significant morbidity and mortality associated with the transplant process requires the application of palliative care concepts throughout the transplant process. By definition, the involved patient population has severe end-stage disease that carries with it significant morbidity and mortality. The disparity between the number of patients needing organs and donors is significant and leaves listed patients with unpredictable waiting times. During this period, the patient’s medical status may worsen and his or her care needs change dramatically. Therefore, transplant medicine is focused on providing life-extending treatments but must always recognize the medical realities and emotional needs of the patients and families involved.

The frequency of organ transplantation has increased dramatically over the past 30 years and has increasingly become a part of patient care. In 2008, there were 27,961 solid organ transplants in the United States, with 1,964 of these procedures occurring in patients less than 18 years old (Table 42-1). Greater experience with the surgical techniques involved with organ transplantation and improved understanding of the etiology of organ rejection will likely lead to increases in the number of patients involved with transplant medicine.

TABLE 42-1 Distribution of Pediatric Solid Organ Transplants in 2008

Organ Number of pediatric transplants 3-Year survival rates
Kidney 773 (39%) 97%
Liver 613 (31%) 88%
Heart 365 (19%) 81%
Intestine 93 (5%) 64%
Lung 45 (2%) 60%

Data compiled from United Network for Organ Sharing 2008 and www.ustransplant.org

The specific criteria to be listed for organ transplantation will vary depending on which organ is involved, but generally patients are referred when the morbidity and mortality associated with their underlying disease is greater than that associated with transplant. Mortality rates reflect a variety of factors, including the impact of the patient’s underlying disease, the technical and medical difficulties associated with the transplant procedure, a variety of post-transplant complications and the availability of other life-extending treatments in the event of transplant failure. Morbidity rates are more difficult to quantify and the impact of transplantation on a patient’s quality of life is similarly challenging. Reported morbidity associated with transplant includes complications from the surgery, chronic organ dysfunction due to ischemic injury or rejection, and the complications associated with long-term immunosuppressive medications. Ultimately, all transplantations require a patient and family commitment to continued medical follow-up and evaluation. Transplantation should not be viewed as a complete cure of the underlying disease process, but rather a transition to a different, chronic medical condition.

Solid organ transplantation is offered in many countries, generally in the more developed and financially sound environments. Patients often have to travel great distances and even cross borders to obtain needed services. In addition, patients do come to the United States seeking organ transplantation. While this is permitted as per United Network for Organ Sharing (UNOS) there are limits as to how many international patients each program can transplant each year.

In the United States, transplant centers are not ranked, but there are national survival rates published on www.ustransplant.org. Patients and families are able to access this data to compare the outcomes of various transplant centers.

Transplant Evaluation

Transplantation is an extraordinarily stressful time from every perspective. Careful patient selection is required due to the physical demands involved with the actual procedure, the psychosocial upheaval involved throughout the process, and the extensive financial and social support required after a transplant. Transplant evaluation is a comprehensive review of the patient’s medical history, current physical condition, psychological and/or emotional status, and available resources. Evaluation is also a time when the family and patient are introduced to the entire transplant team and the process of transplantation. It is essential that the family learn about all aspects of transplantation, including anticipated time on wait lists, potential risks associated with the procedure, and what level of care and lifestyle they can expect post-transplant. The development of stable relationships with the care team during this process can have a lasting impact on patient care throughout the transplant process. At the end of the evaluation process, the patient may be actively listed for transplant, placed on a deferred status until they meet criteria, or be declined for a specific reason. Occasionally, the patient and/or family may elect to not pursue transplantation, may elect to visit other centers, or may decide to postpone becoming listed.

The medical evaluation includes an assessment of the underlying disease process for which the patient was referred, as well as a comprehensive assessment to identify any comorbid conditions that may complicate or preclude transplantation. The substantial risks involved with transplantation and the relative scarcity of available organs mandates an intensive evaluation of the patient’s current and past medical history. Each transplant team will have specific requirements for further testing, but in general patients undergo a variety of physical exams, laboratory tests, radiographic procedures, and consultations. Patients are frequently referred to a transplant program from remote locations with little or no preceding contact with the transplant center. Furthermore, this referral often comes at a time of great crisis for the family because the patient may have recently had a dramatic decline in his or her medical condition. It is not uncommon for transplant centers to repeat testing that has already been completed at the referring institution to confirm results and to evaluate for disease progression.

Each patient being referred for solid organ transplantation will be evaluated by an interdisciplinary team including social workers, financial planners, mental health professionals, and pharmacists. Social workers will assess a family’s ability to handle post transplant care and identify their practical and emotional means of support. There are numerous psychosocial stressors present throughout the transplant process, including living with chronic disease, frequent medical evaluation and treatment, the uncertainty of an organ’s availability, and the substantial requirements for ongoing care after transplantation. In addition to the impact of these stressors on the patient’s and family’s psyche, there are significant associated financial expenses involved in the process. These include the need for frequent admissions, and clinic visits and procedures that are commonly at centers remote from their home. Families may miss work or have travel and food expenses that they would not normally have. Depending on the patient’s insurance, uncovered expenses for office visits and medications can be overwhelming. A social worker will evaluate the family’s ability to cope with these stressors and to identify potential areas of concern that may impact the care of the transplanted patient. Ultimately, the social worker will assist the family in locating and developing the resources and support they will need to successfully navigate this process. A mental health professional will assess the readiness of the patient and family for transplant and evaluate the level of understanding regarding the child’s health and prognosis. There are times when a family and medical team are ready to list for transplant, but the child is not ready. In these instances, the psycho-social support team can be very helpful in navigating issues of assent in these young patients.

At the conclusion of the evaluation process, the patient’s disposition regarding transplant will be determined. Patients are formally presented to the transplant team for discussion and all factors, medical, psychosocial, financial, developmental, and family resource, are taken into consideration. Both medical and psychosocial factors will play a large role in the ultimate decision about whether to list a patient for transplantation. Prior adherence to medical regimens must also be considered. A decision to list a patient will occur when the benefits of a transplant are greater than the predicted morbidity and mortality. There are no clear criteria as to when this threshold is met and therefore listing can be a complicated decision. Importantly, the patient’s quality of life is a vital factor in deciding when to proceed with transplantation. Application of this standard must be tempered by a thorough understanding of the overall health of the patient and care must be taken to not wait too long when comorbid conditions and overall poor health may adversely affect the post-transplant prognosis.

Ethical issues arise when transplant teams are faced with a family with financial and psychosocial limitations. The team must ensure that resources are available to allow the family to overcome these obstacles so that they do not compromise the child’s care. It is well documented that proper post-transplant care is essential to allow for a good outcome. Therefore, in some instances, patients are declined for transplant due to insurmountable psychosocial limitations. On rare occasions, issues of medical foster care are raised to provide a safe environment for the child post-transplant (Table 42-2).

TABLE 42-2 Transplant Team Members

Transplant team member Role
Surgeon Performs transplant surgery
Physician Provides medical care both pre- and post-transplant
Coordinator Responsible for pre- and post-transplant care from a nursing perspective, coordination of care, evaluations and patient and/or family education
Social worker Provides assessment and care around psychosocial needs of family during all phases of transplant process
Psychologist Performs pre-transplant evaluation to identify any contraindications to transplant. Identifies need for continued therapy pre- and post-transplant

Transplant Preparations

Once the determination has been made to list a patient for transplantation, he or she is placed on the national wait list, thus beginning a new period of uncertainty. The waitlist process varies by organ type, with some organs using allocation scores based on disease severity to determine the place on the list. Other organs use pure time on the list, with some preference given to children and adolescents.

Waiting for a transplant can be very stressful for the patient and family. Families are aware that in hoping for a transplant for their child, they are waiting for a tragic event to happen to another family. Understandably, this is very difficult for both older children and their families to process. It is explained that for a donor family, organ donation enables them see some benefit come from their tragic situation.

Waiting times on the list vary depending on the organ, the size of the patient, and region where the patient is listed. This could vary from a day to years. Most families carry a beeper so that the transplant center can reach them quickly when an organ becomes available. Arrangements need to be made in advance for other family responsibilities such as sibling child care, because families need to get to the transplant center in a very short amount of time once an organ is located. Not uncommonly, patients are called in for a transplant only to be sent home without the surgery when complications with the donor arise. Patients can also be listed in more than one region, which may mean double clinic visits and added travel expenses. Certainly, this compounds the time and financial investment for the family.

It can feel as if life is put on hold while a patient is listed for transplant. Because a family needs to be near the transplant center, vacations generally need to be close to home. Activities that have a high exposure to potentially sick contacts should be curtailed. The uncertainty that transplant will occur leads to an extraordinarily stressful time in many patients’ and families’ lives.

It is during this pre-transplant phase that applying palliative care can be most helpful. The patient will frequently be receiving intensive medical care to optimize his or her overall health for when the transplant occurs. These treatments will frequently occur in the face of a progressive, end-stage disease that has high morbidity and mortality without transplant. Balancing the benefits of intensive continued disease-directed therapy with an acceptable quality of life needs to be continually considered and assessed. Open and frank discussions with the patient and family regarding their views of the process, goals, and wishes should occur regularly between the patient and the transplant team. Similarly, palliative care teams can be very helpful in working with the patient’s primary physicians and the transplant teams to ensure that the goals and wishes of the family are continually respected.

It is important to acknowledge that some patients become too ill and no longer remain viable transplant candidates. Furthermore, there are also numbers of waitlist deaths each year, where the appropriate organ is not found in time to save the child. Transplant caregivers then can find themselves in the situation of concurrently managing and maintaining end-stage diseases while simultaneously navigating the dying process. This can feel contradictory to the needs of staying active on a transplant list. It is not uncommon for members of the medical teams to have differing opinions on how to handle these situations. Families are also conflicted with the need to not give up, and yet spare their child any unnecessary pain or discomfort. Discussions about whether a patient can have a DNR order in place and still be active on the transplant list are not infrequent. An example might be a patient with cystic fibrosis who faces potential intubation for progressive end-stage lung disease yet still desires to reach transplantation. In this situation, some patients and/or families elect to proceed with intubation in the hope that an organ will be located in time. Others will choose to pursue more comfort care measures at this time. The palliative care team can be instrumental in guiding the patient, family, and caregivers through these difficult decisions (Fig. 42-1).

Transplant

The actual transplant procedure is that start of a new experience for the patient and his or her family. While many of these patients have lived their lives with a chronic disease, they are now facing procedures, medications, and complications that are vastly different. Each organ transplant has its own set of immediate surgical risks and subsequent recovery period. Post-operatively, patients may require varying periods of ventilatory support and intensive care unit support. Many solid organ transplant patients will receive induction therapy, which provides intensive immediate immunosuppresion in the post-operative period. Depending on the organ and transplant program, this may consist of a few doses of a medication or months of intermittent therapy. This is in contrast with maintenance immunosuppression, which is generally lifelong. Hospitalizations can be brief with discharges within one week or can be prolonged by months should complications arise.

In general, after a transplant, patients will receive immunosuppressive therapy to minimize the chances of rejection. While the degree of immunosuppression differs with each organ, the result is that each patient is at greater risk for infectious complications. For some organs, this risk diminishes over time as immunosuppression is lowered. For others, this risk is significant and lifelong. In general, most solid organ transplant patients are at risk for both acute and chronic rejection. While acute rejection most often occurs in the first few years post transplant and chronic rejection most often after 1 year, these distinctions are not absolute. Therefore, each transplant team will have individualized plans on how to monitor patients for each of these entities. Secondary to these immunosuppressive medications, transplant patients are at risk for long-term complications, including an increased risk of infection, hypertension, renal insufficiency, fluid retention, diabetes, dyslipidemias, seizures, and malignancy. While each patient will have a variable medication regimen, common symptoms experienced by this patient population include gastrointestinal upset, thrush, tremors and headaches, hirsutism, and mood changes (Table 42-3).

TABLE 42-3 Transplant Immunosuppressive Therapies Induction Agents

Medication Mechanism Adverse effects
Induction medications
Rabbit anti-thymocyte globulin (Thymoglobulin) Polyclonal antibody decreases CD4 lymphocytes Persistent lymphopenia
Horse anti-thymocyte globulin (Atgam) Polyclonal antibody against T lymphocytes

Basiliximab (Simulect) Monoclonal antibody to Il-2 receptor complex

Alemtuzumab (Campath) Monoclonal antibody to CD52 Maintenance medications Medication Mechanism Adverse effects Tacrolimus (Prograf) Calcineurin inhibitor Cylcosporine (Neoral/Sandimmune) Inhibition of T-cell activation Mycophenolate mofetil (Cellcept) Inhibition of inosine monophosphate dehydrogenase (IMPDH) with decreased T and B cell proliferation Mycophenolic acid (Myfortic) IMPDH inhibition with decreased T- and B-cell proliferation Azathioprine (Imuran) Purine metabolism antagonist Sirolimus (Rapamune) Suppresses cytokine mediated T-cell proliferation Prednisone Inhibits leukocyte migrations and decreases inflamatory response

A second important consideration after transplant is adequate pain control, both in the immediate post-transplant period and afterward. Patients will generally have multiple lines for intravenous access, often chest tubes or other drains as well as incisions related to their transplant surgery. While most transplant surgeons, physicians, and nurses are well versed in adequate pain control, a palliative care service can be vital at this time to ensure that the patient is receiving the appropriate degree of analgesia. Furthermore, if the palliative care service has a longstanding relationship with the patient and family, they may be aware of differing mechanisms both pharmacologic and nonpharmacologic to help treat a patient’s pain and/or anxiety.

After transplant, patients and families are often adjusting to a new care team with physicians, surgeons, nurses, and hospitals. This period of adjustment can be stressful, and having the continuity of their palliative care team can be very beneficial.

Post-Transplant Period

In the period immediately following transplant, patients and families are adjusting not only to new medical issues but to a new lifestyle as well. Many families have experienced years of coping with the illness that brought them to transplant, and they have developed a level of comfort with the way they feel and how they care for themselves or their child. Post-transplant patients are now forced to revisit this and learn about their body and their care in new ways. Patients and families may also feel that they have been given a second chance. When the transplant was received from a cadaveric donation they are aware of this gift being the result of a tragedy. This can lead to tremendous feelings of guilt as patients and families try to reconcile their joy with the tragedy that another family has experienced.

Patient’s bodies feel different as they incorporate the new organ and begin to feel that it is truly theirs. Patients often wonder about the identity of the donor and whether they might assume some of their donor’s character traits. This can occur with children of all ages and it might affect them in both positive and negative ways. During this post-transplant period many patients or families may wish to write a letter to the donor family. In general, organ procurement organizations will facilitate the communication of this letter to the donor family if they choose to receive it.

Although patients may think about their donors and feel grateful for the gift, one study1 showed that none of the study participants “acknowledged any sign of guilt (for surviving the cadaveric donor or for putting a parent/relative/friend through the physical pain of living related donation). Few had considered that they received any of the donor’s traits. All believed that their sense of self was stronger after transplant with many respondents emphasizing a new, inner strength during the post-transplant period.”1

During the evaluation and as they wait for organs to become available, all families and patients discussed with the medical team that transplant essentially trades one disease process for another. Post-transplant, these patients will face a new set of medical issues. Adjusting to these changes can be a challenging process that varies with the patient’s developmental level. Young children tend to incorporate their new medical regime into their life and continue to work with their parents to manage their medications and medical appointments. Some adults may adjust easily while others may find their new medical regime difficult to adapt to. However, as they become more comfortable with their post-transplant care, they may become less adherent and less anxious when a problem arises, or feel annoyed when their care needs interfere with work or other activities.

Adolescent patients pose a different set of concerns to the transplant professionals. During this stage of development, children feel invincible and are struggling to assert themselves as autonomous individuals. “Risk-taking behaviors function to fulfill developmental needs for independence, autonomy and self-competence.”2 This is the most difficult developmental period for parents and for medical professionals. A healthy teen would be given increasing autonomy and responsibility. For the teen with a transplant, however, parents need to walk a fine line between helping their child learn to manage their own care while they remain involved to ensure that their child is adhering to the medical regime. Their goal is to prepare their child to become an independent adult able to manage his or her own medical care. The foremost concern certainly is that the adolescent will not adhere to the medication regime. In a transplant patient, this can have life-threatening consequences. Teens often want to test the limits of their bodies and don’t fully believe that they need the medications. They may purposefully or subconsciously forget to take their medication for a day or longer. When they realize their error, they may not bring this to the attention of their parents. Additionally, teenagers generally have a strong desire to be like their peers and to feel normal. “During adolescence, a sense of identity and self-understanding is created through social relationships with peers.”3 They may want to feel that they can have days without medications and days just like their healthy friends. Patients whose friends do not know about their transplant may prefer the risk of missing a dose of medication rather than the risk of having a peer ask them about their treatments. There are transplant centers that resist transplanting teens because of these significant concerns about non-adherence.

An additional stressor for the adolescent transplant patient is the eventual transfer of care to an adult center. This is a difficult transition period both medically and psychosocially for the transplant patient. Patients feel abandoned by having to leave a pediatric center, where they may have received care their entire life. Furthermore, adjusting to a new mode of care delivery in an adult center can be challenging to pediatric patients. From a medical standpoint, studies have shown an increased incidence of organ rejection during adolescence.4

In adolescence and adulthood, questions regarding pregnancy post-transplant are often asked. Depending on the health of the transplant patient and the particular organ that they received, the risk of pregnancy is variable. For some organs, such as a lung transplant patient, the risk of experiencing significant and potentially life-threatening rejection is quite high.5 For other patients such as kidney transplant recipients, the risk is likely far less.6 For all transplant patients, they must be aware of the potential risks to a fetus of all medications they are taking.

For the child undergoing a transplant there are many social stressors. There may be extended periods when they miss school and other activities, as well as the continued restrictions of exposure to ill contacts. There are physical changes due to medications such as hair growth or loss, Cushingoid features, and weight gain. In addition, there is the constant feeling of being different from others. “The threat of rejection or infections is a reminder to the patients of the uncertainly of the transplant course. This uncertainty could be viewed as a threat to the adolescent’s sense of self. While some of the patients experienced serious post transplant medical problems, many generally express a determination to focus on the present.”1

There are financial stressors for families, including lost work time and costs inherent in spending time at the hospital with their child. For siblings there can be a sense of deprivation, as more attention must be paid to the patient, fostering any perception that the sick sibling is more important. They may also harbor feelings of guilt or fear that they have caused or contributed to their sibling’s illness. For the patient there may be feelings of guilt as he or she is aware that time spent with them is time away from the sibling.

Children do not perceive death as permanent. This understanding of death gradually develops for children after the age of 5. Children living with life-threatening illness are coping with concerns that are beyond their developmental stage. They must live with the inherent knowledge that death is a reality. “The reality is that children often know much about what is happening to them, regardless of what they have been shielded from or formally told.”7,8 Many of these children and young adults know of other patients who have died and may have experienced a life-threatening event in their own lives.

For the transplant team, there may be judgments that are inherent in having a limited resource with underlying questions about the patients’ worthiness to receive this gift, as well as concerns about other patients who may not survive to transplant. This can become apparent if the patient does not adhere to the treatment regime, particularly if there is a rejection episode.

In time, a recipient becomes more comfortable with his or her changed body and the organ becomes a part of the sense of self. For some this level of comfort is challenged with any medical complications.

Patients and their families may be faced with transitioning from end of life disease to post-transplant recovery and, in some instances, to morbidity from post-transplant complications. Patients can feel well and be more active and then experience complications that quickly reverse these gains. In other instances, there may be gradual post-transplant complications such as living with chronic rejection. Patients and their families may need to shift their mindsets to one of recovery to, once again, facing loss and possibly death.9

End of Life

When a transplanted organ begins to fail, many of the issues surrounding end-stage disease and end of life care are again a reality for a patient and their family. This will certainly vary by organ with various salvage therapies available to each. For example, renal transplant recipients may be faced with considering restarting dialysis. When a transplant organ has failed, an organ recipient and his or her caregivers must consider whether re-transplantation is an option. This decision is generally quite difficult for patients and the transplant team for a variety of reasons. One main consideration would be outcomes following a re-transplant. In some cases, outcomes are worse than with the primary transplant, although this varies significantly with the organ involved.10-12 Additionally, the transplant medications and therapies may have caused problems with other organ systems, such as the kidneys or liver. In some cases, these consequences have resulted in a patient who is not a good re-transplant candidate. Furthermore, it is essential to continue to assess psychological and social factors that could make retransplantation more difficult. Examples would include issues with non-adherence, drug use or poor medical follow up. As each individual transplant center will have its own criteria for primary and for re-transplant patients, it is not uncommon for a patient to be referred to a new program for consideration of re-transplantation. In some cases, this program may be quite a distance from the patient’s home.

Families themselves may be ambivalent about re-transplant. If the first transplant went well, then a family is generally more interested in relisting than if there were significant complications. Some ethicists would argue that with all the waitlist deaths that occur each year, it is unfair to list someone for a second transplant when so many have been waiting so long for their first transplant.

When a patient is relisted for transplant and the organ continues to fail, all of the same issue and feelings return that existed while waiting for the first transplant. Again, medical providers are going down two separate paths; addressing end of life issues and optimizing medical care in order to maintain the patient as a re-transplant candidate. Just as in the initial pre-transplant period, these two paths can seem contradictory to each other both for patients and caregivers alike. For example, giving too much pain medication can cause sleepiness and decrease the ability to stay ambulatory. Yet, we are compelled to not allow our patients to suffer discomfort as much as possible. In this scenario, the palliative care team can be very helpful in walking this fine line. Some medical professionals believe that listing for transplant in general disrupts the normal end of life process. Finding a balance between the two positions must be looked at on an individual patient basis.

Transplant patients have challenges in particular when considering hospice care. For young children these challenges can be even greater. Depending on the hospice and the type of insurance that a child has, there could be a set amount of funds that are allocated once a patient goes into hospice care. At times choices have to be made regarding transplant medications, home nursing services and other services normally offered through hospice care.

Because the goal of transplant is giving life, death in transplant patients requires a different focus of care that is often just as difficult for medical providers as it is for families. Healthcare professionals need continued education and support when helping patients through these challenging times. Having a member of the palliative care team at family meetings and rounds assures that all aspects of care are considered for the patient and family. Medical professionals, especially nursing staff, need both the emotional tools and the educational resources to care for the dying patient.

Clinical Vignette

CK is a 17-year-old boy who was diagnosed with cystic fibrosis as a toddler. At age 12 he was referred to the transplant center for evaluation because of declining pulmonary function and was listed for a double lung transplant. CK waited for 2 years before lungs became available. After transplant CK had several admissions for treatment of infection but was healthy overall.

During this period CK returned to school and for the first time had peers that did not know of his medical background. Initially CK took his medications on time, monitored his pulmonary function by home spirometry, exercised, and was followed closely in transplant clinic. He was independent with most of his care because his mother worked full time. Several years after transplant CK missed several doses of his anti-rejection medications and stopped doing his home spirometry when his friends were around as he struggled to “live like a normal teenager.” Three years after his transplant, CK was diagnosed with chronic rejection. He was again evaluated for a double lung transplant. During the re-evaluation period, CK’s medical status was reviewed and significant concerns were expressed regarding his previous non-adherence. Ultimately, the transplant team believed that this was an isolated event of adolescence and were confident that CK could continue to adhere to the challenging medical regimen required of him with a re-transplant.

CK’s lung function continued to decline rapidly. CK and his father questioned if he would survive long enough to receive a second transplant. His parents were able to discuss procedures and choices around his care with their son but had an increasingly difficult time staying at the hospital during his lengthy admissions. CK worked closely with mental health providers at the transplant center and began to clarify his end of life wishes, which included doing everything possible to receive a transplant but dying peacefully if transplant would no longer be an option. Fortunately, CK did receive a second double lung transplant. The transplant team continues to work closely with CK and his parents around managing his medical regime, discussing changing roles as CK moves toward adulthood and coping with the sadness and anxiety the family has experienced as they have been repeatedly confronted by the fragility of life.

References

1 Durst C.L., Horn M.V., Maclaughlin E.F., Bowman C.M., Starnes V.A., Woo M.S. Psychosocial responses of adolescent cystic fibrosis patients to lung transplantation. Pediatr Transplant. 2001;5:27-31.

2 Millstein S.G., Ingra V. Theoretical models of adolescent risk-taking behavior. In: Wallander J.L., Siegel I.J., editors. Adolescent health problems. New York: Guilford; 1995:52-71.

3 Sroufe L.A., Cooper R.G., Dehart G. Child Development: its nature and course, ed 3. New York: McGraw Hill, 1996.

4 Bell L.E., Bartosh S.M., Davis C.L., Dobbels F., Al-Uzri A., Lotstein D., Reiss J., Dharnidharka V.R. Adolescent transition to adult care in solid organ transplantation: a consensus conference report. Am J Transplant. 2008;8:2230-2242.

5 Armenti V.T., Radomski J.S., Moritz M.J., Gaughan W.J., McGrory C.H., Coscia L.A. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Cecka, Terasaki. Clinical transplants. 2003. Los Angeles

6 Zachariah M.S., Tornatore K.M., Venuto R.C. Kidney transplantation and pregnancy. Curr Opin Organ Transplant. 2009;14:386-391.

7 Sourkes B.M. Armfuls of time: the psychological experience of the child with a life-threatening illness. Pittsburgh: University of Pittsburgh Press, 1995.

8 Bluebond Langer M. Private worlds of dying children, Princeton, NJ. Princeton University Press, 1978.

9 Berzoff J., Silverman P.R., editors. Living with dying. a handbook for end-of-life healthcare practitioners. New York: Columbia University Press, 2004.

10 Aurora P., Edwards L.B., Christie J.D., Dobbels F., Kirk R., Rahmel A.O., Stehlik J., Taylor D.O., Kucheryavaya A.Y., Hertz M.I. Registry of the International Society for Heart and Lung Transplantation: Twelfth Official Pediatric Lung and Heart/Lung Transplantation Report-2009. J Heart Lung Transplant. 2009;28:1023-1030.

11 Kanter K.R., Vincent R.N., Berg A.M., Mahle W.TM., Forbess J.M., Kirshbom P.M. Cardiac retransplantation in children. Ann Thoracic Surg. 2004;78:644-649.

12 Shen Z.Y., Zhu Z.J., Deng Y.L., Zheng H., Pan C., Zhang Y.M., Shi R., Jiang W.T., Zhang J.J. Liver retransplantation: report of 80 cases and review of the literature. Hepatobiliary Pancreat Dis Int. 2006;5(2):180-184.