Sana Ullah, MB ChB, FRCA - Children’s Medical Center, Dallas
A 15-year-old female with a history of orthotopic heart transplantation 2 months prior presents with intermittent fevers, abdominal pain, diarrhea and enlarged lymph nodes in the neck. Post-transplant lymphoproliferative disease (PTLD) is confirmed by lymph node biopsy and a PET-CT scan of her body. Which of the following risk factors in the recipient at the time of heart transplantation is MOST LIKELY associated with the development of PTLD?
Correct!
Wrong!
Question of the Week 321
While immunosuppressant therapy is critical for preventing organ rejection after transplantation, one of the serious risks is the development of various malignancies in the recipient as the body’s immune surveillance systems are compromised. Many of these malignancies are caused by viruses, in particular Epstein-Barr virus (EBV) and Human Papilloma Virus. A study from 2006 showed the incidence of post-transplant lymphoproliferative disease (PTLD) is approximately 5% in children after heart transplant. The majority of these cases were of B-cell origin and of these, 87% were EBV positive. The probability of survival after diagnosis was 75% at 1 year and 68% at 3 years (1). The most common sites for PTLD are the upper airway (hypertrophy of tonsils and adenoids) and the gastrointestinal tract.
Risk factors for PTLD include the following: (1) Negative EBV recipient and positive EBV donor serology, (2) younger age, as younger patients are more likely to be EBV-naïve (EBV infections occur more frequently in older children and adults), and (3) multiple rejection episodes, as these require higher and more frequent doses of immunosuppressant medications.
Clinical features vary and include fever, weight loss, night sweats, gastrointestinal disturbances, hypertrophy of tonsils and adenoids, and lymph node enlargement in the neck, axilla and groin. Diagnostic evaluation includes clinical examination, chest x-ray, ultrasound of the abdomen and lymph nodes, computed tomography and magnetic resonance imaging, and lymph node biopsy. More recently, positron emission tomography-computed tomography has become the imaging modality of choice (2,3).
Treatment depends on the type and severity of the disease but usually starts with a reduction of immunosuppressive drug therapy to allow the patient to mount an immune response to EBV. The obvious risk with this approach is acute rejection. Targeted therapy with rituximab, a chimeric anti-CD20 monoclonal antibody, can be used for CD20 positive B-cell lymphomas.
Cytomegalovirus (CMV) is the most common viral infection after transplantation and is associated with an increased risk of rejection, coronary allograft vasculopathy, and graft failure (4).
A high panel reactive antibody (PRA) titer is associated with an increased risk of rejection.
References
1) Webber SA, Naftel DC, Fricker FJ, et al. Pediatric Heart Transplant Study. Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study. Lancet. 2006; 367(9506): 233-239.
2) Schubert S. Lymhoproliferative disorders in pediatric heart transplant recipients. In: Canter C, Everitt MD, Burch M et al. (Eds). ISHLT Monograph Series Vol 13. Pediatric Heart Transplantation. UAB Printing; 2019.
3) Addonizio LJ, Boyle GJ. Post-transplant malignancy: Risk factors, incidence, diagnosis, treatment. In: Canter C, Kirklin JK (Eds). ISHLT Monograph Series Vol. 2. Pediatric Heart Transplantation. Elsevier; 2007.
4) Schowengerdt KO, Azeka E. Infection following pediatric heart transplantation. In: Canter C, Kirklin JK (Eds). ISHLT Monograph Series Vol. 2. Pediatric Heart Transplantation. Elsevier; 2007.
Risk factors for PTLD include the following: (1) Negative EBV recipient and positive EBV donor serology, (2) younger age, as younger patients are more likely to be EBV-naïve (EBV infections occur more frequently in older children and adults), and (3) multiple rejection episodes, as these require higher and more frequent doses of immunosuppressant medications.
Clinical features vary and include fever, weight loss, night sweats, gastrointestinal disturbances, hypertrophy of tonsils and adenoids, and lymph node enlargement in the neck, axilla and groin. Diagnostic evaluation includes clinical examination, chest x-ray, ultrasound of the abdomen and lymph nodes, computed tomography and magnetic resonance imaging, and lymph node biopsy. More recently, positron emission tomography-computed tomography has become the imaging modality of choice (2,3).
Treatment depends on the type and severity of the disease but usually starts with a reduction of immunosuppressive drug therapy to allow the patient to mount an immune response to EBV. The obvious risk with this approach is acute rejection. Targeted therapy with rituximab, a chimeric anti-CD20 monoclonal antibody, can be used for CD20 positive B-cell lymphomas.
Cytomegalovirus (CMV) is the most common viral infection after transplantation and is associated with an increased risk of rejection, coronary allograft vasculopathy, and graft failure (4).
A high panel reactive antibody (PRA) titer is associated with an increased risk of rejection.
References
1) Webber SA, Naftel DC, Fricker FJ, et al. Pediatric Heart Transplant Study. Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study. Lancet. 2006; 367(9506): 233-239.
2) Schubert S. Lymhoproliferative disorders in pediatric heart transplant recipients. In: Canter C, Everitt MD, Burch M et al. (Eds). ISHLT Monograph Series Vol 13. Pediatric Heart Transplantation. UAB Printing; 2019.
3) Addonizio LJ, Boyle GJ. Post-transplant malignancy: Risk factors, incidence, diagnosis, treatment. In: Canter C, Kirklin JK (Eds). ISHLT Monograph Series Vol. 2. Pediatric Heart Transplantation. Elsevier; 2007.
4) Schowengerdt KO, Azeka E. Infection following pediatric heart transplantation. In: Canter C, Kirklin JK (Eds). ISHLT Monograph Series Vol. 2. Pediatric Heart Transplantation. Elsevier; 2007.
