biology

Post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorder is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Post-transplant lymphoproliferative disorder rather than just read about it. In short: Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia.

Key takeaways

Post-transplant lymphoproliferative disorder belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Post-transplant lymphoproliferative disorder to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Post-transplant lymphoproliferative disorder from memory before moving on to harder problems.

Reference excerpt

Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B cells may undergo mutations which will render them malignant, giving rise to a lymphoma. In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant.

Signs and symptoms Symptoms of PTLD are highly variable and nonspecific, and may include fever, weight loss, night sweats, and fatigue. Symptoms may be similar to those seen in infectious mononucleosis (caused by EBV). Pain or discomfort may result from lymphadenopathy or mass effect from growing tumors. Dysfunction may occur in organs affected by PTLD. Lung or heart involvement may result in shortness of breath. Laboratory findings may show abnormally low white blood cell, red cell counts, and platelet counts. In addition, serum uric acid and lactate dehydrogenase levels may be elevated, while serum calcium levels may be decreased. All of these findings together can suggest tumor lysis syndrome.

Causes The disease is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein–Barr virus (EBV). Production of an interleukin-10, an endogenous, pro-regulatory cytokine, has also been implicated. In immunocompetent patients, Epstein-Barr virus can cause infectious mononucleosis in adolescents, which is otherwise asymptomatic in children during their childhood. However, in immunosuppressed transplant patients, the lack of T-cell immunosurveillance can lead to the proliferation of these EBV-infected B-lymphocytes. However, calcineurin inhibitors (tacrolimus and ciclosporin), used as immunosuppressants in organ transplantation inhibit T cell function, and can prevent the control of the B cell proliferation. Depletion of T cells by use of anti-T cell antibodies in the prevention or treatment of transplant rejection further increases the risk of developing post-transplant lymphoproliferative disorder. Such antibodies include ATG, ALG and OKT3 (muromonab-CD3). Polyclonal PTLD may form tumor masses and present with symptoms due to a mass effect, e.g. symptoms of bowel obstruction. Monoclonal forms of PTLD tend to form a disseminated malignant lymphoma.

Diagnosis

Definitive diagnosis is achieved by biopsying the involved tissue, which will reveal lymphoproliferative neoplasia. Most lesions will show malignant B cells, whereas a minority will show T cell neoplasia. CT imaging may show enlarged lymph nodes or a focal mass. PET scan may be helpful in the evaluation, which may show an increase in metabolic activity (PET avid) lesion, potentially guiding decisions on where to direct biopsies. Neurologic symptoms, such as confusion or focal weakness, which may suggest involvement of the nervous system. This may be evaluated with an MRI of the brain with gadolinium based contrast and lumbar spinal tap with testing of the cerebral spinal fluid for EBV viral levels. The presence of respiratory symptoms, such as cough or shortness of breath, in the setting of immunosuppression may suggest infection. Opportunistic infections may present in a similar fashion to PTLD. Evaluation with sputum culture for bacteria, Pneumocystis carinii, and acid fast bacilli, and fungal infections are often helpful.

Treatment PTLD may spontaneously regress on reduction or cessation of immunosuppressant medication, and can also be treated with addition of anti-viral therapy. In some cases it will progress to non-Hodgkin's lymphoma and may be fatal. A phase 2 study of adoptively transferred EBV-specific T cells demonstrated high efficacy with minimal toxicity. PTLD exhibits tissue that is effaced by morphologically homogenous clonal proliferation of B, T, or NK cells with a malignant phenotype . Preventive treatment options for PTLD development require EBV DNA-level monitoring through bloodwork if the EBV level. Based on elevated EBV values, reducing immunosuppressants is recommended, and prophylactic rituximab should be considered if EBV fails to respond to immunosuppression. Prophylactic rituximab is successful as a treatment option in low dosages to effectively and safely reduce EBV viremia. Another important consideration in treatment is the histologic subtype of PTLD; if it is non-destructive polymorphic lesions that have indolent behavior do not require aggressive treatment, while other malignant PTLDs are often treated similarly to their analogous lymphoma.

Epidemiology PTLD is the second most common malignancy that occurs as a complication following solid organ transplantation (skin cancer is the most common). Less commonly, PTLD occurs after hematopoietic stem cell transplantation. The incidence varies by the type of transplantation: the lowest rates are seen with bone marrow transplants and liver transplants. The highest rates of PTLD are seen with lung and heart transplants, which is primarily due to the need for higher levels of immunosuppression. The incidence of PTLD is highest in the first year after transplantation; roughly 80 percent of cases after transplant occur in the first year. Transplantation of unmatched or mismatched HLA bone marrow also increase the risk of PTLD. The main risk factors for PTLD are the degree of immune suppression and the presence of Epstein-Barr virus. Specifically, higher levels of T cell immunosuppression increase the risk PTLD. Individuals who have never been infected by the Epstein-Barr virus (EBV negative) who receive an organ from a donor with prior EBV infection are 24 times more likely to develop PTLD. Similarly, CMV mismatching (with a CMV negative recipient from a CMV positive donor) increases the risk of PTLD.

References

External links

Illustrations

Worked examples

Example 1 — a first encounter with Post-transplant lymphoproliferative disorder

Start with the simplest possible case. Write down what Post-transplant lymphoproliferative disorder claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Post-transplant lymphoproliferative disorder before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Post-transplant lymphoproliferative disorder ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Post-transplant lymphoproliferative disorder

In research: Post-transplant lymphoproliferative disorder appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Post-transplant lymphoproliferative disorder in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Post-transplant lymphoproliferative disorder is common in secondary-school and first-year university syllabi. It links to neighbouring topics Epstein–Barr virus–associated diseases, Lymphoma, Transplantation medicine, so understanding it makes those chapters shorter.
In everyday life: Look for Post-transplant lymphoproliferative disorder outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Post-transplant lymphoproliferative disorder in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Post-transplant lymphoproliferative disorder means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Post-transplant lymphoproliferative disorder out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Post-transplant lymphoproliferative disorder in simple terms?

Why does Post-transplant lymphoproliferative disorder matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Post-transplant lymphoproliferative disorder?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Post-transplant lymphoproliferative disorder.