Post transplant lymphoproliferative disorder

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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 World Health Organization (WHO) classification system, into 4 subtypes:

• Early hyperplastic lesions
• Polymorphic lesions
• Monomorphic lesions
• Classic Hodgkin-type lymphomas

Pathophysiology

• 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 characterized by the production of interleukin-10.

• Resemblance to large cell lymphomas

• 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 is Epstein-Barr virus.

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

• Post transplant lymphoproliferative disorder is very rare.
• 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.