Post transplant lymphoproliferative disorder

WikiDoc Resources for Post transplant lymphoproliferative disorder
Articles
Most recent articles on Post transplant lymphoproliferative disorder Most cited articles on Post transplant lymphoproliferative disorder Review articles on Post transplant lymphoproliferative disorder Articles on Post transplant lymphoproliferative disorder in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Post transplant lymphoproliferative disorder Images of Post transplant lymphoproliferative disorder Photos of Post transplant lymphoproliferative disorder Podcasts & MP3s on Post transplant lymphoproliferative disorder Videos on Post transplant lymphoproliferative disorder
Evidence Based Medicine
Cochrane Collaboration on Post transplant lymphoproliferative disorder Bandolier on Post transplant lymphoproliferative disorder TRIP on Post transplant lymphoproliferative disorder
Clinical Trials
Ongoing Trials on Post transplant lymphoproliferative disorder at Clinical Trials.gov Trial results on Post transplant lymphoproliferative disorder Clinical Trials on Post transplant lymphoproliferative disorder at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Post transplant lymphoproliferative disorder NICE Guidance on Post transplant lymphoproliferative disorder NHS PRODIGY Guidance FDA on Post transplant lymphoproliferative disorder CDC on Post transplant lymphoproliferative disorder
Books
Books on Post transplant lymphoproliferative disorder
News
Post transplant lymphoproliferative disorder in the news Be alerted to news on Post transplant lymphoproliferative disorder News trends on Post transplant lymphoproliferative disorder
Commentary
Blogs on Post transplant lymphoproliferative disorder
Definitions
Definitions of Post transplant lymphoproliferative disorder
Patient Resources / Community
Patient resources on Post transplant lymphoproliferative disorder Discussion groups on Post transplant lymphoproliferative disorder Patient Handouts on Post transplant lymphoproliferative disorder Directions to Hospitals Treating Post transplant lymphoproliferative disorder Risk calculators and risk factors for Post transplant lymphoproliferative disorder
Healthcare Provider Resources
Symptoms of Post transplant lymphoproliferative disorder Causes & Risk Factors for Post transplant lymphoproliferative disorder Diagnostic studies for Post transplant lymphoproliferative disorder Treatment of Post transplant lymphoproliferative disorder
Continuing Medical Education (CME)
CME Programs on Post transplant lymphoproliferative disorder
International
Post transplant lymphoproliferative disorder en Espanol Post transplant lymphoproliferative disorder en Francais
Business
Post transplant lymphoproliferative disorder in the Marketplace Patents on Post transplant lymphoproliferative disorder
Experimental / Informatics
List of terms related to Post transplant lymphoproliferative disorder

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: PTLD;

Overview

Post-transplant lymphoproliferative disorder (also known as PTLD) is defined as a lymphoid (immune cells) and/or plasmacytic proliferations (rapid increase) due to therapeutic immunosuppression after organ transplantation especially in the patients who are undergoing solid organ or allogeneic (donor) hematopoietic stem cell transplantation. Patients with post-transplant lymphoproliferative disorder may develop serious complications of transplantation with infectious mononucleosis-like lesions due to Epstein-Barr virus (EBV) or polyclonal polymorphic B-cell hyperplasia. In some cases, B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma. The malignant cell clone can become the dominant proliferating cell type, leading to a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant. Post transplant lymphoproliferative disorder arises from germinal center or post-germinal center B cells (B-PTLD), which are normally involved the production of antibodies and durable memory B cells. Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965. According to World Health Organization (WHO) classification system, post transplant lymphoproliferative disorder may be classified into 4 subtypes: early hyperplastic lesions, polymorphic lesions, monomorphic lesions, and classic Hodgkin-type lymphomas. Post transplant lymphoproliferative disorder is very rare, and the prevalence of post transplant lymphoproliferative disorder remains unknown. Post transplant lymphoproliferative disorder is more commonly observed among young patients. The medical treatment for post transplant lymphoproliferative disorder, includes: immunosuppression, antiviral therapy, interferon alpha therapy, CD20 antibody therapy, and chemotherapy.

Historical Perspective

• Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965.

Classification

• Post transplant lymphoproliferative disorder may be classified according to 2008 World Health Organization (WHO) classification system, into 3 subtypes:

Category	Subtype
Early hyperplastic lesions	Infectious mononucleosis-type acute illness Polyclonal B cell proliferation No evidence of malignant transformation Plasmacytic hyperplasia
Polymorphic lesions	Evidence of malignant transformation Nuclear atypia Necrosis Lymphoid architecture distortion Found in immunocompetent patients
Monomorphic lesions	B-cell lymphomas Diffuse large B-cell lymphoma Burkitt’s/Burkitt’s-like lymphoma Plasma cell myeloma Monoclonal lymphoid proliferations T-cell lymphomas Peripheral T-cell lymphoma Gamma/delta T-cell lymphoma T-natural killer (NK) lymphoma
Other types	Hodgkin’s disease Plasmacytoma like lymphoma

Pathophysiology

• It is understood that post transplant lymphoproliferative disorder is the result of B cell proliferation induced by Epstein-Barr virus (EBV) infection.
• 90 to 95 percent of patients with post transplant lymphoproliferative disorder shows positive serologic of infection especially with Epstein-Barr virus (EBV) infection.
• Membrane proteins associated with EBV plays a major role in contribute to B cell growth and survival.
  • LMP-1-Latent membrane protein 1
  • LMP-2A-Latent membrane protein 2
  • EBNA-2(Epstein-Barr nuclear antigen 2) and
  • EBNA-LP(Epstein-Barr nuclear antigen 2 ladder protein)

• Post transplant lymphoproliferative disorder arises from germinal center or post-germinal center B cells (B-PTLD) , which are normally involved the production of antibodies and durable memory B cells.
• The pathogenesis of post transplant lymphoproliferative disorder is also characterized by the production of interleukin-10.

• The overexpression of bcl-2 has been associated with the development of post transplant lymphoproliferative disorder.
• On gross pathology, characteristic findings of post transplant lymphoproliferative disorder, include:
  • Resemblance to large cell lymphomas
  • No remarkable findings

• On microscopic histopathological analysis, characteristic findings of post transplant lymphoproliferative disorder, include:
  • Resemblance to large cell lymphomas
  • Large lymphoid cells with a diameter (2x a resting lymphocyte)

Causes

• The most common causes of post transplant lymphoproliferative disorder are:
  • Epstein-Barr virus
  • Immunosuppression
  • Recipient age: under 25 years
  • Ethnicity
  • History of pretransplant malignancy
  • Fewer HLA matches
  • Treatment with ATG

Differentiating Post Transplant Lymphoproliferative Disorder from Other Diseases

• Post transplant lymphoproliferative disorder must be differentiated from other diseases that cause fatigue, weight-loss, and fever, such as:
• Infectious mononucleosis
• Diffuse large B-cell lymphoma
• Lymphoblastic lymphoma
• Blastic mantle cell lymphoma (MCL)

Epidemiology and Demographics

Incidence

• The incidence of post transplant lymphoproliferative disorder is approximately 20 percent of all cancers especially with solid organ transplantation.
• The incidence of post transplant lymphoproliferative disorder in liver transplants is approximately 1 to 2 percent.
• The incidence of post transplant lymphoproliferative disorder in renal transplant is approximately 1 to 3 percent.
• The incidence of post transplant lymphoproliferative disorder in heart transplant is approximately 2 to 6 percent.
• The incidence of post transplant lymphoproliferative disorder in lung transplant is approximately 2 to 9 percent.
• The incidence of post transplant lymphoproliferative disorder in intestinal or multi organ transplants is approximately as high as 11 to 33 percent.
• The prevalence of post transplant lymphoproliferative disorder remains unknown.

Age

• Post transplant lymphoproliferative disorder is more commonly observed among young patients.

Gender

• Females are slightly more affected with post transplant lymphoproliferative disorder than men.

Race

• There is no racial predilection for post transplant lymphoproliferative disorder.

Risk Factors

• The most common risk factors in the development of post transplant lymphoproliferative disorder is B cell neoplasm associated with Epstein-Barr infection.

Natural History, Complications and Prognosis

• The majority of patients with post transplant lymphoproliferative disorder are symptomatic at the time of diagnosis.
• Early clinical features include fatigue, fever, and weight-loss.
• If left untreated, patients with post transplant lymphoproliferative disorder may progress to develop organ failure.
• The most common complication of post transplant lymphoproliferative disorder is fatal infection.
• Prognosis is generally poor, and the 5-year survival rate of patients with post transplant lymphoproliferative disorder is approximately 37- 61%.

Diagnosis

Symptoms

• Post transplant lymphoproliferative disorder is usually asymptomatic.
• Symptoms of post transplant lymphoproliferative disorder may include the following:

• Persistent fatigue
• Loss of appetite
• Nausea
• Vomiting
• Unexplained weight loss

Physical Examination

• Patients with post transplant lymphoproliferative disorder usually appear pale and malnourished.
• Physical examination may be remarkable for:

• Swelling in the lymph nodes in the neck or underarms
• Fever
• Night sweats
• Unexplained weight loss

Laboratory Findings

• There are no specific laboratory findings associated with post transplant lymphoproliferative disorder.

Imaging Findings

• There are no imaging findings associated with post transplant lymphoproliferative disorder.

Treatment

Medical Therapy

• The medical treatment for post transplant lymphoproliferative disorder, includes:

• Immunosuppression
• Antiviral therapy
• Interferon alpha therapy
• CD20 antibody therapy
• Chemotherapy

• Post-transplant lymphoproliferative disorder may regress spontaneously on reduction or cessation of immunosuppressant medication anti-viral therapy.

Surgery

• Surgery is not recommended for patients with post transplant lymphoproliferative disorder.

Prevention

• There are no primary preventive measures available for post transplant lymphoproliferative disorder.