blood and immune - ferreri

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Questions and Answers

What is the main purpose of monoclonal antibodies as a diagnostic or treatment approach?

  • To recognize a single epitope and destroy tumor cells (correct)
  • To create a broad immune response against various antigens
  • To prevent transplant rejection
  • To stimulate the production of multiple antibodies

Which Nobel Prize-winning discovery was essential for the development of monoclonal antibodies?

  • The structure of DNA
  • The discovery of T-cells
  • The development of hybridoma technology (correct)
  • The process of vaccination

What is the function of the variable region in a monoclonal antibody?

  • To link different components of the immune system.
  • To provide structural support to the antibody
  • To trigger an immune response
  • To recognize and bind to the antigen (correct)

Which type of cells are primarily responsible for producing monoclonal antibodies?

<p>Plasma cells (D)</p> Signup and view all the answers

What is the key advantage of using monoclonal antibodies that act on different epitopes of the same protein?

<p>It allows for alternative strategies if the first treatment fails. (D)</p> Signup and view all the answers

In target discovery, what can be the target of a treatment using monoclonal antibodies?

<p>Either the signaling molecule or the receptor (A)</p> Signup and view all the answers

Why is it important to produce monoclonal antibodies that act on different epitopes?

<p>To avoid overlapping activity and reduce effectiveness. (C)</p> Signup and view all the answers

What is the purpose of immortalizing B-cells with myeloma cells in hybridoma technology?

<p>To enable the continuous reproduction and production of monoclonal antibodies (D)</p> Signup and view all the answers

What is the primary goal of humanizing mouse antibodies?

<p>To reduce the risk of immunological recognition and rejection in humans (A)</p> Signup and view all the answers

What is a key difference between monoclonal antibodies and small molecule drugs?

<p>Monoclonal antibodies are usually administered intravenously or subcutaneously. (D)</p> Signup and view all the answers

How are small molecules typically eliminated from the body?

<p>By the liver and kidneys (A)</p> Signup and view all the answers

What is a notable characteristic of small molecules compared to monoclonal antibodies regarding the blood-brain barrier?

<p>Small molecules can cross the blood-brain barrier more easily (D)</p> Signup and view all the answers

Why is it important to consider the structure of monoclonal antibodies in relation to immunogenicity?

<p>To reduce the risk of triggering an immune response (B)</p> Signup and view all the answers

According to the nomenclature rules for monoclonal antibodies, what does the suffix 'mab' indicate?

<p>That it is a monoclonal antibody (C)</p> Signup and view all the answers

In immunotherapy, what is characteristic of passive immunotherapies?

<p>They use ready-to-use products like monoclonal antibodies or cytokines. (B)</p> Signup and view all the answers

What is the primary mechanism of action of monoclonal antibodies against lymphomas through 'blocking'?

<p>Recognizing and interfering with a receptor or ligand interaction (C)</p> Signup and view all the answers

What is the role of bispecific monoclonal antibodies in treating lymphomas?

<p>To engage T-lymphocytes and activate them against the tumor (D)</p> Signup and view all the answers

Which of the following is a common target for monoclonal antibody drugs used in lymphoma treatment?

<p>CD-19 (D)</p> Signup and view all the answers

What is a notable side effect associated with bispecific antibodies and CAR-T cell therapy?

<p>Chemokine release syndrome (CRS). (B)</p> Signup and view all the answers

What is the purpose of using antibody-drug conjugates in lymphoma treatment?

<p>To deliver a toxic substance specifically to tumor cells. (D)</p> Signup and view all the answers

What is the most common chromosomal translocation associated with follicular lymphomas?

<p>Translocation (14:18) (B)</p> Signup and view all the answers

Which gene is often amplified and activated in follicular lymphoma due to chromosomal translocation?

<p>Bcl-2 gene (B)</p> Signup and view all the answers

On which chromosome is the p53 gene located?

<p>Chromosome 17 (A)</p> Signup and view all the answers

Which of the following is part of the standard staging workup for follicular lymphoma?

<p>CT scan (A)</p> Signup and view all the answers

What does the 'T' in the TNM staging system stand for?

<p>Tumor (C)</p> Signup and view all the answers

Which staging system is most commonly used for lymphomas?

<p>Ann Arbor staging system (A)</p> Signup and view all the answers

According to the Ann Arbor staging system, what defines stage 3?

<p>Lesions on both sides of the diaphragm (A)</p> Signup and view all the answers

Which organs, when involved, automatically define stage 4 disease in the Ann Arbor staging system?

<p>Liver and bone marrow (B)</p> Signup and view all the answers

What is a characteristic of 'B symptoms' in lymphoma?

<p>Night sweats (C)</p> Signup and view all the answers

How is fever defined as a systemic symptom in lymphoma?

<p>Fever of unknown origin above 38°C (A)</p> Signup and view all the answers

What percentage of body weight loss over six months is considered a 'B symptom'?

<p>10% (C)</p> Signup and view all the answers

What letter is added to the Ann Arbor stage to indicate systemic symptoms are present?

<p>B (A)</p> Signup and view all the answers

What is a notable characteristic of indolent lymphomas regarding treatment?

<p>May warrant observation for a period (D)</p> Signup and view all the answers

What type of drug has significantly improved the prognosis of follicular lymphoma in the last 20 years?

<p>Anti-CD20 monoclonal antibodies (A)</p> Signup and view all the answers

Which of the following drugs is commonly used in follicular lymphoma treatment combinations?

<p>Rituximab (A)</p> Signup and view all the answers

What does 'C' stand for in the chemotherapy combination CVP?

<p>Cyclophosphamide (B)</p> Signup and view all the answers

What is the mechanism of action of cyclophosphamide?

<p>Interfering with DNA binding (A)</p> Signup and view all the answers

Which bispecific antibody is approved for use in follicular lymphoma?

<p>Mosunetuzumab (D)</p> Signup and view all the answers

What is the most important initial step in managing a patient with follicular lymphoma?

<p>Evaluating prognosis, symptoms, and patient priorities (B)</p> Signup and view all the answers

What is a consideration when deciding on treatment for follicular lymphoma to avoid overtreatment?

<p>Aggressiveness of the disease and patient's age (C)</p> Signup and view all the answers

What type of cells are most often affected in chronic lymphocytic leukemia (CLL)?

<p>Monoclonal B lymphocytes (D)</p> Signup and view all the answers

What characterizes the progression of CLL?

<p>Sequential genetic abnormalities accumulate (D)</p> Signup and view all the answers

After what age does the incidence of CLL significantly increase?

<p>60 (C)</p> Signup and view all the answers

What is the established cause of CLL?

<p>Unknown (D)</p> Signup and view all the answers

What percentage of CLL cases exhibit familial patterns?

<p>8.8% (B)</p> Signup and view all the answers

What is a common initial sign of CLL diagnosed incidentally?

<p>Cytopenia with lymphocytosis (C)</p> Signup and view all the answers

Which of the following is a typical 'B symptom' associated with CLL?

<p>Drenching night sweats (C)</p> Signup and view all the answers

What is a common clinical sign observed in CLL patients?

<p>Lymphadenopathy (A)</p> Signup and view all the answers

What laboratory test is essential for CLL diagnosis due to its hallmark characteristic?

<p>Assessment of B cell clonality (B)</p> Signup and view all the answers

What is a typical laboratory finding in CLL patients?

<p>Lymphocytosis (D)</p> Signup and view all the answers

What finding indicates significant immunosuppression in CLL?

<p>Hypogammaglobulinemia (D)</p> Signup and view all the answers

According to the International Workshop on CLL, what is one of the diagnostic criteria?

<p>A sustained peripheral blood lymphocyte count &gt;10,000/μL (C)</p> Signup and view all the answers

Which cells must be identified as monoclonal B cells for diagnosis of CLL via the International Workshop on CLL diagnostic criteria?

<p>Peripheral blood lymphocytes (D)</p> Signup and view all the answers

What is one of the cell surface markers expressed by the clonal B-cells in CLL?

<p>CD5 (A)</p> Signup and view all the answers

What is the significance of P53 deletion or mutations in CLL?

<p>Reduced sensitivity to chemotherapy (A)</p> Signup and view all the answers

What is a transformation of CLL that is considered a more aggressive form of the disease?

<p>Richter syndrome (D)</p> Signup and view all the answers

What is a commonly used class of agents in elderly patients for treating CLL?

<p>Alkylating agents (A)</p> Signup and view all the answers

Which factor is considered when considering initiating treatment for CLL?

<p>Severe cytopenias (C)</p> Signup and view all the answers

What is the goal of treating patients with Ibrutinib?

<p>Managing or preventing progression (B)</p> Signup and view all the answers

What is the role of Venetoclax in treating CLL?

<p>It's an anti-BCL2 enzyme (D)</p> Signup and view all the answers

According to the ESMO guidelines, what considerations are vital for patients to consider for first-line treatment?

<p>Mutations in genes encoding for immunoglobulins and P53 abnormalities (A)</p> Signup and view all the answers

Which comorbidity index is often used to assess survival outcomes in CLL, particularly for geriatric patients?

<p>Charlson score (D)</p> Signup and view all the answers

How often should monitoring take place if CLL is not treated at the onset?

<p>Every six months (B)</p> Signup and view all the answers

What is the primary challenge associated with treating CLL, leading to increased mortality?

<p>COVID-19 (B)</p> Signup and view all the answers

In relapsed CLL, what factors are key in decision-making for subsequent treatment?

<p>Status of p53 gene, duration of remission, and time to relapse (B)</p> Signup and view all the answers

What is the most common type of non-Hodgkin's lymphoma?

<p>Diffuse large B-cell lymphoma (DLBCL) (A)</p> Signup and view all the answers

In DLBCL, approximately what percentage of cases arise in extra-nodal organs?

<p>40% (B)</p> Signup and view all the answers

What is a typical immunophenotype marker for DLBCL?

<p>CD20 (B)</p> Signup and view all the answers

The 14;18 translocation in DLBCL is often associated with abnormalities in which gene?

<p>BCL-6 (D)</p> Signup and view all the answers

Which phenotype, determined through gene expression profiling, is associated with more favorable survival in DLBCL?

<p>Germinal center B cell (D)</p> Signup and view all the answers

What is a primary component of the International Prognostic Index (IPI) used for DLBCL?

<p>Number of extra-nodal sites (C)</p> Signup and view all the answers

What does the term 'double expresser lymphoma' refer to in the WHO classification of lymphoid neoplasms?

<p>Co-expression of MYC and BCL2 (C)</p> Signup and view all the answers

The 'grey zone' between Burkitt's lymphoma and DLBCL is characterized by which of the following?

<p>Overlapping features between the two lymphomas (A)</p> Signup and view all the answers

For elderly patients with DLBCL, what is the preferred initial treatment?

<p>R-CHOP 21 (C)</p> Signup and view all the answers

Why is there a limit to the number of CHOP doses you can give?

<p>Cumulative dose limit of Doxorubicin/Adriamycin (B)</p> Signup and view all the answers

What is the most common cause of CNS relapse in DLBCL?

<p>Inability of R-CHOP to cross the blood-brain barrier (C)</p> Signup and view all the answers

Unlike in follicular lymphoma, why is maintenance rituximab typically NOT indicated after R-CHOP treatment for DLBCL?

<p>It does not provide additional benifit (B)</p> Signup and view all the answers

Which drug is often required to fight DLBCL that has spread to the CNS?

<p>High-dose methotrexate (C)</p> Signup and view all the answers

What is a key characteristic feature observed under microscopic examination of Burkitt's lymphoma?

<p>&quot;Starry sky&quot; pattern (C)</p> Signup and view all the answers

What genetic abnormality is associated with Burkitt's lymphoma?

<p>MYC rearrangement (B)</p> Signup and view all the answers

Hodgkin lymphoma (HL) shares similarities in natural history and clinical behavior with what other type of neoplastic disease?

<p>A solid tumor (D)</p> Signup and view all the answers

What is the hallmark cellular characteristic used to identify Hodgkin lymphoma?

<p>Reed-Sternberg cells (B)</p> Signup and view all the answers

Which of the following factors has the strongest association with Hodgkin Lymphoma?

<p>EBV infection (C)</p> Signup and view all the answers

What is the most common initial clinical presentation of Hodgkin lymphoma?

<p>Enlargement of peripheral lymph nodes (C)</p> Signup and view all the answers

In most Hodgkin Lymphoma cases, how does the disease typically spread?

<p>To neighboring lymph nodes (C)</p> Signup and view all the answers

Which blood test results are typically seen in patients with Hodgkin Lymphoma?

<p>Normal peripheral blood counts (C)</p> Signup and view all the answers

Which of the following is NOT a main differential diagnoses for Hodgkin Lymphoma?

<p>Diabetes (D)</p> Signup and view all the answers

What percentage of Hodgkin Lymphoma cases are classified as Nodular Lymphocyte Predominant Hodgkin Lymphoma?

<p>5% (A)</p> Signup and view all the answers

In Classic Hodgkin Lymphoma, which subtype is known to be the most common?

<p>Nodular sclerosis (D)</p> Signup and view all the answers

Which marker is most useful for distinguishing Hodgkin lymphoma cells in CD20 negative lymphomas?

<p>PAX5 (C)</p> Signup and view all the answers

Which of the following is one of the main goals of Hodgkin Lymphoma treatment?

<p>Reducing toxicity (B)</p> Signup and view all the answers

What is the most common form of secondary cancer observed in lymphoma patients?

<p>Acute myeloid leukemia (B)</p> Signup and view all the answers

Which of the following is included in ABVD combination chemotherapy?

<p>Bleomycin (B)</p> Signup and view all the answers

What is a common symptom patients with Hodgkin Lymphoma may have?

<p>Pruritus (A)</p> Signup and view all the answers

What is the most dangerous toxicity associated with Dacarbazine?

<p>Vomiting (C)</p> Signup and view all the answers

What is the typical median age at diagnosis for Multiple Myeloma (MM)?

<p>66 years (A)</p> Signup and view all the answers

Pathologic plasma cells in myeloma commonly secrete?

<p>Monoclonal immunoglobulins and free light chains (D)</p> Signup and view all the answers

What percentage of Multiple Myeloma cases involve the secretion of IgG?

<p>60% (B)</p> Signup and view all the answers

When Multiple Myeloma involves only free chains, it is called?

<p>Micromolecular multiple myeloma (A)</p> Signup and view all the answers

Multiple Myeloma is associated with which of the following?

<p>Unknown etiopathogenesis (C)</p> Signup and view all the answers

Which of the following is the first step in the multistep process of Multiple Myeloma development?

<p>MGUS (Monoclonal Gammopathy of Undetermined Significance) (C)</p> Signup and view all the answers

What leads to the autonomic growth of myeloma cells and increased drug resistance?

<p>Loss of stroma dependence (D)</p> Signup and view all the answers

Translocation involving chromosome 14 in Multiple Myeloma often affects which gene?

<p>IgH (immunoglobulin heavy chain) (A)</p> Signup and view all the answers

In the interaction between myeloma cells and bone marrow stromal cells, what is activated?

<p>All of the above (D)</p> Signup and view all the answers

Activation of RANK by RANKL from osteoblasts results in?

<p>Increased osteoclastic activity and bone destruction (C)</p> Signup and view all the answers

In the pathogenesis of Multiple Myeloma, tumor cell growth in the bone marrow results in?

<p>Myeloftisis (B)</p> Signup and view all the answers

What percentage of Multiple Myeloma patients are asymptomatic at diagnosis?

<p>One third (B)</p> Signup and view all the answers

In what percentage of cases do Multiple Myeloma patients present with bone destruction and bone pain?

<p>70-80% (B)</p> Signup and view all the answers

Renal involvement is seen in what percentage of Multiple Myeloma cases?

<p>25% (A)</p> Signup and view all the answers

The compression of the spinal cord in Multiple Myeloma is considered what?

<p>An oncological emergency (B)</p> Signup and view all the answers

Hyperviscosity is most commonly found in which type of Multiple Myeloma?

<p>IgM (C)</p> Signup and view all the answers

What are the two main factors essentially used to diagnose multiple myeloma?

<p>Clonality demonstration and symptomatic disease (C)</p> Signup and view all the answers

Which test is used to demonstrate clonality in Multiple Myeloma?

<p>Serum/urine protein electrophoresis (B)</p> Signup and view all the answers

What is a key use of Beta2-microglobulin in Multiple Myeloma?

<p>Identifying the stage of the disease (A)</p> Signup and view all the answers

Normal plasma cells are typically positive for?

<p>CD19 (A)</p> Signup and view all the answers

Which of these findings is part of the CRAB criteria for Myeloma Defining Events?

<p>Creatinine &gt;2mg/dL (C)</p> Signup and view all the answers

What is the MAIN feature of MGUS?

<p>Serum monoclonal protein (non-IgM type) &lt;30 g/L (B)</p> Signup and view all the answers

What is the percentage range of clonal bone marrow cells for smoldering myeloma?

<p>Clonal bone marrow plasma cells between 10-60% (A)</p> Signup and view all the answers

Principles of therapy for patients with Multiple Myeloma includes which factor?

<p>Autologous stem cells transplantation results in an increased overall survival (B)</p> Signup and view all the answers

Concerning treatment, isolated plasmacytoma of bone is best managed with which strategy?

<p>Radiation therapy (C)</p> Signup and view all the answers

What is recommended for patients with indolent myeloma?

<p>Watch and wait approach (A)</p> Signup and view all the answers

What class of active drugs are Dexamethasone and Prednisone?

<p>Steroids (A)</p> Signup and view all the answers

What class of active drug is Thalidomide?

<p>Antiangiogenic and IMID (C)</p> Signup and view all the answers

What type of therapy involves Idecabtagene vicleucel (Abecma), Ciltacabtagene autoleucel (Carvykti), and Equecabtagene autoleucel?

<p>CAR T-cell therapies (B)</p> Signup and view all the answers

Flashcards

Monoclonal Antibody

An immunoglobulin molecule produced in the lab to recognize a single epitope for diagnostic/treatment purposes.

B-Cells

These cells are able to recognize and bind to antigens; key for antibody production and immune response.

Target Discovery

The process of discovering and validating therapeutic targets related to disease pathology through signaling molecules and receptors.

CHO Cells

Cells are used to produce large quantities of monoclonal antibodies through gene transfer.

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Immunogenicity

The ability of a substance to provoke an immune response.

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Immunotherapy

Treatment that uses the body's immune system to fight diseases like cancer.

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Bispecific antibodies

Monoclonal antibodies that bind to two different targets simultaneously, enhancing immune cell engagement with tumor cells.

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Antibody-drug conjugates

Antibodies linked with potent toxins to selectively kill tumor cells.

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"Wait and watch" strategy

Following and observing the patient for indolent lymphoma. There is no treatment to cure these patients.

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Indolent Lymphomas

Lymphomas with a slow growth rate; typically incurable but manageable.

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Follicular Lymphoma

Most common subtype of indolent lymphoma representing 20%-25% of all lymphomas.

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Tumor flare

An excessive expansion of reactive cells in the tumor microenvironment during treatment; can appear as disease progression.

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Translocation (14;18)

Chromosomal abnormality in follicular lymphomas involving chromosome 14 and 18.

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Bcl-2 Gene

A gene on chromosome 18, when translocated, becomes activated, inhibiting apoptosis.

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Follicular Lymphoma Staging

Contrast-enhanced CT scan, FDG PET, and bone marrow biopsy.

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TNM Staging

System used to define tumor extension in solid tumors.

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Ann Arbor Staging System

Divides the body into regions above and below the diaphragm.

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Stage 3 Follicular Lymphoma

Disease on both sides of the diaphragm.

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Stage 4 Follicular Lymphoma

Multifocal/bilateral involvement of external organs or involvement of the liver/bone marrow.

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Bulky Disease

Considered a lesion larger than one-third of the thoracic diameter in the mediastinum.

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Systemic Symptoms

Night sweats, weight loss, and fever.

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Cyclophosphamide

Chemotherapy drug that interferes with the binding in DNA.

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Mosunetuzumab

Antibody targets CD20 on lymphoma cells and CD3 on T cells.

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ESMO Guidelines

Guidelines for treatment of hematological disorders.

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Treatment Considerations

Tumor burden, stage, and patient's general health.

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R-CHOP

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

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Bendamustine

A purine analogue that damages tumor cell DNA.

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Rituximab Maintenance

Maintenance therapy post-chemo improves progression-free survival.

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Chemo-free Induction

Uses immunomodulators instead of cytotoxics.

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CAR T-cell therapy

Process of collecting, engineering, and infusing T cells.

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Graft Versus Leukemia Effect

Donor immune cells eliminate recipient malignant cells.

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Splenic Marginal Zone Lymphoma

Marginal zone lymphoma with massive infiltration of the spleen.

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Chronic Lymphocytic Leukemia (CLL)

Most common leukemia in adults, marked by a buildup of non-multiplying mature cells.

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CLL Progression Factors

Primarily linked to genetic factors, trigger remains unknown; proliferation is due to microenvironment interactions and genetic mutations.

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CLL Incidence

Increases with age, peaking after 60; more common in males; underlying cause is undetermined.

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CLL Etiology

Cause is unclear, links to microorganisms and environmental contaminants are suspected, but lack conclusive evidence.

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CLL Symptoms

Small multiple lymph node enlargements; bacterial infections may indicate CLL.

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B symptoms in CLL

Weight loss, fevers, and night sweats; suggestive of underlying malignancy, warranting investigation.

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Mosquito Bite Sensitivity & CLL

Heightened reaction to mosquito bites is a notable symptom in older individuals with CLL.

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Lymphadenopathy in CLL

Enlarged lymph nodes are discrete, movable and non-tender.

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Lymphocytosis

The increase in lymphocytes (>5,000 per microliter) is evident in lab tests.

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B Cell Clonality in CLL

B cell clonality is confirmed through the expression of light chains and immunoglobulin gene rearrangement analysis

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Hypogammaglobulinemia in CLL

Immunosuppression leading to reduced levels of immunoglobulins; bacterial infections are a major risk.

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IWCLL diagnostic criteria

Sustained lymphocyte count over 10,000/μL, BM aspirate >30% lymphocytes; monoclonal B cells.

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Smudge Cells

Cells disrupted in smears; Increased small, round lymphocytes with scant cytoplasm.

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Immunophenotype of CLL Cells

These cells show positivity for CD5, CD43, and CD23, distinguishing CLL from other lymphomas.

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Deletion or mutation of P53

This is due to reduced sensitivity to chemotherapy, assess with FISH.

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Differential Diagnosis of CLL

Infections & other B-cell lymphomas primary considerations; spectrum from indolent to aggressive.

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Rai Staging System

Used to stage CLL by assessing lymphocytosis, lymphadenopathy, splenomegaly, anemia, and thrombocytopenia.

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Binet Classification

Used to stage CLL by assessing hemoglobin levels, platelet counts, and the number of affected lymph node areas.

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Richter syndrome

Shift towards diffuse large B cell lymphoma; aggressive, poses a therapeutic challenge.

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Treatment Initiation

Used to determine when to start treatment, including the severity of cytopenias, autoimmune disorders, splenomegaly, or transformation

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Alkylating Agents

They disrupt the process of DNA Binding.

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Novel CLL treatment options

PI3K inhibitor; Bruton tyrosine kinase inhibitor; Anti-BCL2 enzyme.

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CGA for CLL treatment

Based on comorbidities and life expectancy; GO-GO, Slow-GO, non-GO.

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BTK-inhibitors: Ibruinib or acalabrutinib

For treatment of CLL patients with symptoms, but is indicated when patients have mutated or deletion of the P53 gene.

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Venotoclax

Can be used in first-line treatment of Cll, often combined with Obinutuzumab because it works better that way..

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DLBCL

A type of non-Hodgkin's lymphoma; the most common aggressive B-cell lymphoma.

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Epidemiology

The study of disease patterns and distribution in populations, here, focusing on ages 60-70 in patients with DLBCL.

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Etiology

The causes and mechanisms of disease development; DLBCL etiology includes immunodeficiency and chronic infections (e.g., EBV).

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Morphology

The study of cell structure; DLBCL cells appear diffused and can infiltrate beyond the lymph node.

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Immunophenotype

The use of antibodies to identify cells; DLBCL cells are usually CD20+ and CD79a+.

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Cytogenetics and Molecular Biology

Analysis of chromosomal abnormalities and genes; some DLBCL cases show translocations or complex karyotypes.

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Gene Expression Profiling (GEP)

Classification of lymphomas by gene expression patterns to predict prognosis and treatment response.

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Germinal Center B-cell Phenotype (GCB)

DLBCL subtype associated with better survival compared to the activated B cell (ABC) phenotype; identified by gene expression.

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International Prognostic Index (IPI)

A scoring system used to assess prognosis of DLBCL based on factors like age, stage, and LDH levels.

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Double Expresser Lymphoma

Co-expression of MYC and BCL2 in DLBCL cells, indicating a more aggressive form of the lymphoma.

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DLBCL Primary to the Testis

Rare form of DLBCL that recurs in the contralateral testis, requiring radiation to prevent relapse.

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Consolidation IFRT

Use of radiation therapy to areas showing residual disease on PET scans after initial treatment.

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CNS Prophylaxis

A strategy to prevent the spread of DLBCL to the CNS using drugs that cross the blood-brain barrier.

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Tafasitamab

A potent CAR T-cell therapy drug that targets CD19+ lymphoma cells

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Polatuzumab Vedotin

An agent that binds to the CD79B to interfere with the mitotic spindle

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Hodgkin Lymphoma (HL)

A cancer originating in the lymphatic system, identified by Reed-Sternberg cells.

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Importance of HL dissemination

Distinguishing HL from other lymphomas and predicting dissemination.

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Reed-Sternberg Cells

The hallmark cells of Hodgkin Lymphoma, key for diagnosis.

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ABVD

Drug combination used as the standard treatment for HL.

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EBV and HL Prognosis

Suggests a possible link to better outcomes in younger HL patients.

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Common HL presentation

Enlargement of lymph nodes in the neck and mediastinum.

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Lymph node characteristics

Site, size, morphology, pain, fixation, and texture.

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Lymphadenectomy

A procedure to obtain tissue for diagnosing HL.

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Copper Levels in HL

Elevated copper levels, once used but now unreliable for HL suspicion.

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Infective Lymphadenopathies

Viruses, bacteria, fungi (EBV, CMV, Toxoplasmosi, HIV).

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Nodular Lymphocyte Predominant Hodgkin Lymphoma

Associated with high grade transformation.

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Classic Hodgkin Lymphoma

The most common subtype with subgroups like nodular sclerosis.

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NFkB signalling pathway

Genetic alterations that influence the NFkB signalling pathway.

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HL treatment goals

Cure and reduce cardiovascular and gonadal toxicity.

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ABVD combination

Doxorubicin, bleomycin, vinblastine, and dacarbazine.

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Multiple Myeloma

A neoplastic proliferation of a single clone of plasma cells producing monoclonal immunoglobulin.

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Myeloma Characterization

Pathologic plasma cells that secrete monoclonal immunoglobulins and free light chains.

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Multiple Myeloma Progression

A multistep disease that starts with MGUS, then smoldering myeloma, and then intramedullary myeloma. Finally, extra-medullary myeloma and myeloma cell line.

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Stroma Dependence

In myeloma, stroma dependence is lost, leading to autonomous growth and drug resistance.

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MM-Stroma Interaction

Interaction of myeloma cells with bone marrow, activating pathways for proliferation and inhibiting apoptosis.

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RANK/RANKL Pathway in MM

An imbalance in tumor cells, osteoblasts, and stromal cells that activates the RANK/RANKL pathway, leading to bone destruction.

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Pathogenesis of MM

It is caused by tumor cells in bone marrow, secreted molecules causing renal injury, and cytokine production increasing bone resorption.

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Clinical Symptoms of MM

Tumor cells result in bone marrow infiltration that leads to bone pain, hypercalcemia, coagulopathy and neurological symptoms.

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Diagnosing Multiple Myeloma

Detection via serum/urine protein electrophoresis, immunofixation, and clonal cells in bone marrow.

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Protein Electrophoresis

Demonstrates clonality in gamma globulin with abnormalities in the electrophoresis profile.

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Bone Marrow Examination

Cytological examination shows plasma cells >10%, immunophenotyping identifies clonality and markers.

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MGUS (Monoclonal Gammopathy of Undetermined Significance

Serum monoclonal protein <30 g/L, clonal bone marrow plasma cells <10%, absence of end-organ damage.

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Smoldering Multiple Myeloma

Serum monoclonal protein ≥30 g/L; clonal bone marrow cells between 10-60%; no symptoms or organ abnormality.

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Multiple Myeloma Diagnosis

Needs clonal bone marrow plasma cells >10% (or biopsy-proven) and at least one CRAB feature.

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CRAB Criteria

Calcium elevated, Renal failure, Anemia, and Bone lesions on radiography.

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Durie-Salmon Staging

Divided into Stage I, II, and III; based on hemoglobin, calcium, osteolytic lesions, immunoglobulins, and light chain levels.

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International Staging System (ISS)

Considers serum albumin and B2-microglobulin levels.

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Principles of MM Therapy

Chemotherapy, autologous stem cell transplantation, and novel agents.

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Isolated plasmacytoma treatment

radiation therapy with a possible 10-year OS of 50%.

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Active Drugs for MM

Dexamethasone, Prednisone; Chemo: Melphalan, Doxorubicin, Cyclophosphamide.

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Transplant -eligible Induction

Includes: Lenalidomide, + bortezomid + dexa ,CTX + bortezomib + dexa ,

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Tafamidis

Drugs that help block ATTR/cardiac amyloidosis.

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Systemic Amyloidosis

Weight loss, fatigue, renal failure, and neuropathies.

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Study Notes

  • Median overall survival for multiple myeloma (MM) patients is longer due to new therapeutic strategies.
  • Plasma cell disorders are a part of the group, they are very rare tumors.
  • Some of the plasma cell disorders are curable, and others are treated for several years with an acceptable quality of life.
  • These tumors are the second after the lymphomas among hematological malignancies.
  • Multiple myeloma cells originate in plasma cells and germinal center B cells.
  • Tumor cells express mature markers in the B lineage through recombination, hypermutation, and isotype switching in the germinal center.

Multiple Myeloma

  • MM is a neoplastic proliferation of a single clone of plasma cells producing monoclonal immunoglobulin.
  • Some myelomas do not release immunoglobulins.
  • The main site of proliferation is the bone marrow, with an incidence of 3-4/100,000.
  • MM constitutes 1% of malignant diseases and 10% of all hematological diseases.
  • Median age at diagnosis is 66.
  • Myeloma is characterized by pathologic plasma cells that secrete monoclonal immunoglobulins and free light chains (k ο λ).

MM Secretions

  • 60% of cases involve IgG secretion.
  • 20% of cases involve IgA secretion.
  • 20% of cases involve only free chains, referred to as micromolecular multiple myeloma.
  • 1% of cases involve IgM, IgD, or IgE secretion.
  • In rare cases, plasma cells do not secrete immunoglobulins.

Etiopathogenesis

  • The etiopathogenesis of MM remains unknown.
  • No genetic predispositions are known, but some chromosomal abnormalities are associated.
  • Environmental factors (ionizing radiations, toxins) could be a possible etiology.
  • Antigenic stimulation and association with rheumatoid arthritis may be important in MM development.

Multiple Myeloma as a Multistep Disease

  • MM development often occurs as a multistep process:
  • MGUS (Monoclonal Gammopathy of Undetermined Significance)
  • Smoldering myeloma
  • Intramedullary myeloma
  • Extramedullary myeloma
  • Myeloma cell line
  • Karyotypic abnormalities increase during these processes, with p18 deletion, MYC dysregulation, and p53 mutation detected in later phases.
  • Some cases do not follow this multistep process and are directly diagnosed as multiple myeloma.
  • Myeloma progressively loses stroma dependence, resulting in autonomic cell growth and increased drug resistance.
  • Chromosomal abnormalities associated with MM include:
  • Long arm of chromosome 14 (IgH gene)
  • Translocations involving chromosomes 4, 8, 16, and 11:
  • MYC, BCL-1, CCND3 which stimulates growth of tumor cells.

Stroma Interaction

  • MM interacts with the stroma, particularly bone marrow stromal cells through:
  • Adhesion molecules
  • Vascular factors such as VEGF:
  • Chemokines and cytokines (IL6, TNF1).
  • These interactions activate pathways within stromal and myeloma cells such as:
  • PI3K
  • JAK/STAT3
  • MEK/ERK
  • NF-kB, leading to continuous proliferation of tumor cells and inhibition of apoptosis.

MM Microenvironment

  • The relationship between tumor cells and osteoblasts/stromal cells in the bone is mediated by:
  • VLA4 and CAM1: activates RANK/RANKL pathway.
  • RANKL secreted by osteoblasts interacts with RANK, increasing osteoclastic activity and bone destruction.
  • MM cells interact with:
  • Lymphocytes: generate immunosuppression.
  • Stromal cells: produce cytokines.
  • Endothelial cells: result in angiogenesis, which is important for tumor dissemination and growth.
  • Osteoclasts: cause bone reabsorption.
  • Osteoblasts: cause bone formation inhibition.

Pathogenesis of Multiple Myeloma

  • Tumor cells grow in the bone marrow, leading to myelophthisis, compression, and bone destruction.
  • Secreted molecules, especially light chains, affect the kidneys, causing acute or chronic renal injury.
  • Cytokine production contributes to increased bone resorption, hypercalcemia, and hypogammaglobulinemia.

Clinical Presentation of Multiple Myeloma

  • One third of patients are asymptomatic.
  • 70-80% of patients present with bone destruction and pain due to:
  • Osteolytic lesions (skull, spine, pelvis, imbalance of OPG/RANKL).
  • Osteoporosis (affects mainly elderly patients).
  • Pathological fractures.
  • 25% experience renal involvement caused by:
  • Hypercalcemia: leads to osmotic diuresis and hypovolemia.
  • Light chain proteinuria (Bence Jones proteinuria): light chains sediment in renal tubules and interstitium, causing renal failure.
  • Urate nephropathy.
  • Amyloid glomerulopathy: rare form of nephrotic syndrome.
  • Infections: recurrent pyelonephritis.
  • 80% of patients present with anemia due to:
  • Cytokine activity released by stromal cells (IL6, TNF, IL-1b).
  • Renal dysfunction.
  • Myelophthisis.
  • Hemolytic anemia caused by autoantibodies (more common in lymphoma).
  • Reduction of vitamins.
  • Infections (pneumonia, pyelonephritis) occur in 25% of patients, commonly caused by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, E. coli).
  • Few patients experience neurological symptoms:
  • Compression by soft tissue plasmacytoma.
  • Hyperviscosity.
  • Hypercalcemia.
  • Compression of the spinal cord.
  • Spinal cord compression is an oncological emergency requiring intervention within 5-6 days to prevent irreversible paraplegia.
  • Peripheral neuropathy due to amyloidosis, is another form of neurological involvement.
  • Some patients experience bleeding due to:
  • Platelet dysfunction.
  • Acquired coagulopathy.
  • Amyloidosis.
  • Hyperviscosity (IgM).
  • 10% of patients present with hyperviscosity, commonly in IgM but also in IgA and IgG (IgM>IgA>IgG) causing:
  • Increased blood flow resistance.
  • Reduced blood flow in microcirculatory system.
  • Thrombotic and hemorrhagic events (oronasal bleeding, visual disturbance, headache, dizziness, coma).
  • Heart failure.
  • Marrow infiltration releases cytokines which lead to bone pain, hypercalcemia, coagulopathy and neurological symptoms.
  • Monoclonal proteins are result of abnormal protein production, which cases renal failure, hyperviscosity, amyloidosis, immunodeficiency

Diagnosis of Multiple Myeloma

  • Diagnosis relies on two main factors:
    1. Presence of clonal cells, demonstrated through:
    • Serum/urine protein electrophoresis, confirmed by immunofixation.
    • Presence of polyclonal Ig.
    • Presence of free light chains in serum or urine.
    • Detection of clonal cells in bone marrow by aspirate and biopsy.
    1. Symptomatic disease:
    • Peripheral blood count, peripheral smear, and CBC are performed to find abnormal renal function, anemia or hyperuricemia.
    • Serum creatinine, azotemia, calcemia, uricemia, LDH, PCR, and β2-microglobulin are assessed. β2-microglobulin is a marker used to identify disease stage and guide treatment.
    • Bone imaging (X-rays, MRI, TC scan, and PET) is performed.

Clonality Demonstration

  • Protein electrophoresis demonstrates clonality in gamma globulin with abnormalities in the electrophoresis profile.
  • Free light chain assessment demonstrates clonality by measuring unbound λ and k light chains.
  • This is diagnostic for micromolecular myeloma, non-secretory myeloma, systemic light chain amyloidosis, and light chain deposition disease.
  • It is related to the prognosis of MGUS and smaller MM. Free light chain detection is also monitored during MM follow-up to define stringent complete remission (sCR).
  • Normal FLC-R k/λ range is 0.26-1.65; values outside indicate clonality and require investigation for neoplastic cells.

Bone Marrow Examination:

  • Bone marrow examination confirms MM diagnosis based on:
  • Cytological examination: plasma cells >10%.
  • Immunophenotype: clonality, high CD38, high CD138, CD56+, low CD45 and CD19-. . Normal plasma cells are positive for CD19, which is often lost in MM cells.
  • Cytogenetics: useful for prognosis but not diagnosis (karyotype and FISH).
  • Histology: plasma cells >10%, distribution (diffuse, nodular, interstitial, fibrosis), and clonality (immunohistochemistry: k and λ).
  • MM plasma cells: CD38+, CD56+, CD19-
  • Normal plasma cells: CD38+++, CD56-, CD19+
  • Classical MM cells appear as plasma cells with a peripheral nucleus and abundant vesicular cytoplasm (due to abnormal protein)
  • Binucleated cells with masses in cytoplasm = Russell bodies
  • Cells with multiple immunoglobulin globules in cytoplasm = Mott cells
  • Clonal cell infiltration in bone marrow

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