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This is a variety of conditions featuring neoplastic proliferations of mature lymphocytes in blood. Examples include B-cell chronic lymphocytic leukemia (CLL), hairy cell leukemia, Prolymphocytic leukemias, and T-cell proliferations.
Chronic Lymphocytic Leukemias
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What is the most common adult leukemia in the US and Europe? This predominantly affects the older age group (median age ~55-60 years), and has a higher incidence in males than females.
B-cell Chronic Lymphocytic Leukemia (CLL)
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B-cell chronic lymphocytic leukemia (CLL) is biologically heterogenous. What are the two variants, and what are the differences between them?
- Pre-germinal center variant: "unmutated" immunoglobulin gene (IgH); more aggressive
- Post-germinal center variant: "mutated" immunoglobulin gene (IgH); less aggressive
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What is the most common cause of B-cell Chronic Lymphocytic Leukemia? What are some other possible etiologies?
- Majority are idiopathic
- Possible genetic predisposition; possible occupational or chemical exposure (reported increased incidence in agricultural workers)
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What is the most common clinical presentation of B-cell CLL? What are other symptoms and PE findings?
- Frequently asymptomatic: unexpected finding on routine CBC
- Symptoms (when present) are nonspecific: fatigue, weight loss, fever, night sweats
- PE: often unremarkable -- lymphadenopathy may be present, but usually not marked; may have hepatomegaly
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How is B-cell CLL diagnosed?
- Lymphocytosis (>5,000)
- Immunophenotyping by flow cytometry: immunoglobulin light chain restriction (kappa or lambda, but not both)
- Bone marrow exam: traditionally done, but may not be required
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Identify the Leukemia from the blood smear below. Identify defining characteristics.
- B-Cell Chronic Lymphocytic Leukemia (B-CLL)
- Lymphocytosis of small, mature-appearing lymphocytes
- Very condensed nuclear chromatin ("soccer ball" nuclei)
- Numerous "Smudge" Cells (smashed lymphocytes
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Identify the leukemia from the blood smear below. Identify defining characteristics.
- B-Cell Chronic Lymphocytic Leukemia (B-CLL)
- "Soccer Ball" Nuclei & "Smudge" Cells
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Identify the leukemia from the bone marrow biopsy below. What is a defining characteristic?
- B-Cell Chronic Lymphocytic Leukemia (B-CLL)
- Near total replacement of marrow with lymphocytes
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What B-cell markers does B-CLL express? T-cell marker?
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What is the key diagnostic test in B-CLL?
Flow Cytometry
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What lab findings are associated with B-CLL?
- Anemia
- Thrombocytopenia
- Absolute neutrophil count normal; percent neutrophils decreased
- DAT -- 1%+ at diagnosis; increases with duration of disease
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What disease is defined by the presence of a small monoclonal B-cell population in blood. By definition, there are less than 5,000 clonal lymphocytes. Other criteria for this diagnosis include: normal PE (NO lymphadenopathy or hepatosplenomegaly); NO B symptoms; NO autoimmune or infectious disease
Monoclonal B-Cell Lymphocytosis (MBL)
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Monoclonal B-cell Lymphocytosis (MBL) is relatively common, and its incidence increases with age. MBL probably precedes all cases of what related disease, though the majority of MBL patients never transform to this.
CLL
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What is the treatment for Monoclonal B-cell Lymphocytosis (MBL)?
No treatment necessary
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How is B-cell Chronic Lymphocytic Leukemia (B-CLL) differentiated from Small Lymphocytic Leukemia (SLL)?
- CLL: >5,000 clonal lymphocytes
- SLL: <5,000 clonal lymphocytes
- Phenotype, appearance in lymph node, and bone marrow identical. Considered one disease in WHO
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According to the Rai and Binet Staging Systems for B-CLL, what puts a patient at low risk? what puts the patient at intermediate risk? And high risk?
- Low Risk: lymphocytosis only
- Intermediate Risk: lymphocytosis plus lymphadenopathy or hepatosplenomegaly
- High Risk: presence of bone marrow involvement
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The majority of patients with B-CLL have what type of course? What is the median survival?
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What are four predictors of an aggressive course in B-CLL?
- Rapid lymphocyte doubling time
- Presence of cytogenetic abnormalities
- Diffuse involvement of bone marrow
- Bone marrow compromise
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What are the five complications related to B-CLL?
- Infections
- Cytopenias
- Autoimmune Disorders
- Mass Effects (due to bulky lymphoadenopathy)
- Transformation to histologically aggressive disease
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What is the most frequent cause of death in B-CLL? What is this predominantly due to? What is the most common site?
- Infections
- Hypogammaglobinemia -- poor opsonization, impaired response to new antigenic challenges
- Respiratory Tract -- pneumonia most common
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What drug, used to treat B-CLL, has major effects on the T-cell system, and is consequently very immunocompromising? How is this combated?
- Fludarabine
- Combine it with Rituxan, with or without cyclophosphamide
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What transformation to an aggressive large cell lymphoma, usually occuring in a lymph node, is seen in B-CLL? What does this result in?
- Richter Syndrome
- Poor response to therapy; short survival
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When do we treat B-CLL?
- When Symptomatic, or when one of the following indications are met:
- Rapid Lymphocyte Doubling Time
- Bulky Lymphadenopathy
- Bone Marrow Compromise
- Autoimmune Phenomena
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What has become the treatment of choice for B-CLL for many hematologists? What are two major side effects?
- Fludarabine + Rituxan + Cyclophosphamide
- Myelosuppressive & Immunocompromising
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What B-CLL treatment has a potential to cure the disease, but is only utilized in young patients with aggressive disease due to significant morbidity and mortality?
Allogenic Stem Cell Transplant
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This leukemia type is an uncommon, distinctive lymphocytic leukemia. It occurs predominantly in the older population, and has a higher incidence in males. Cytopenias are often seen with this disease (leukopenia, anemia, thrombocytopenia, neutropenia, adn monocytopenia common). Often massive splenomegaly is seen. Symptoms are often non-specific and include fatigue, weakness, lethargy; abdominal discomfort and early satiety due to splenomegaly; and recurrent pyrogenic infections due to neutropenia -- cutaneous infections are common.
Hairy Cell Leukemia
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Identify the leukemia from the blood smear below:
Hairy Cell Leukemia
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Identify the leukemia from the bone marrow biopsy below. What is characteristic for this disease?
- Hairy Cell Leukemia
- "Fried Egg" appearance
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What is the key diagnostic test for Hairy Cell Leukemia? What is an older test used to diagnose this (not anymore)?
- Flow Cytometry -- demonstrates clonality of lymphocytes
- TRAP Stain
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What is the primary treatment for Hairy Cell Leukemia?
Cladribine: single 7 day infusion causes durable complete response in 80% or more
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This disease is characterized by a lymphocytosis of T-cells with multilobulated or convoluted nuclei. This is not very common in the US, and is more common in african americans than caucasians. This disease is related to Human T-Cell Lymphocytotrophic Virus-1 (HTLV-1), and in fact was the first virus proven to be directly oncogenic in humans.
Adult T-Cell Leukemia/Lymphoma (ATLL)
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What is required for the diagnosis of Adult T-cell Leukemia/Lymphoma (ATLL)?
Demonstration of positive serologies for HTLV-1
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Identify the leukemia from the blood smear below:
- Adult T-Cell Leukemia/Lymphoma (ATLL)
- "Florette-like" nuclei
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Adult T-cell Leukemia/Lymphoma (ATLL) may present as leukemia plus or minus lymphadenopathy. It may present as a lymphoma -- lymphadenopathy without blood involvement. Most patients eventually develop the leukemic picture, if not present at diagnosis. How does this usually present in the US?
A leukemia with lymph node enlargement
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What is the diference in median age of onset of ATLL in Japan versus in the US? How is the course of the disease different?
- Japan: mid 50s; smoldering, indolent and acute forms occur
- US: onset in 30s; aggressive; skin lesions and hypercalcemia common
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What is the treatment for Adult T-cell Leukemia/Lymphoma? What are survival rates?
- Treatment largely ineffective
- Survival in US poor -- median survival <1 year
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