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Lymphoma and Leukemia

Lymphoma

 
Etiology 
  • The exact cause of lymphoma in dogs is not fully understood, but it’s believed to be multifactorial.

  • Potential factors include:

    • Infections: Viruses or bacteria may play a role.

    • Environmental factors: Exposure to certain chemicals, such as phenoxyacetic acid herbicides, or strong magnetic fields.

    • Genetic mutations: Chromosomal changes or genetic abnormalities.

    • Immune system issues: Abnormal immune responses may contribute.

  • Genetic studies have shown that lymphoma in dogs can be classified into different groups based on how aggressive they are biologically.

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Clinical Signs
  • Generalized Lymphadenopathy (swollen lymph nodes):

    • 80-85% of dogs with lymphoma show non-painful, enlarged lymph nodes that are easily felt under the skin.

    • Affected lymph nodes are typically movable and firm.

  • Organ-Specific Symptoms:

    • Alimentary lymphoma (affecting the digestive system):

      • Vomiting, diarrhea, weight loss, and poor appetite (due to malabsorption of nutrients).

      • Severe GI signs with widespread involvement of the intestines.

    • Mediastinal lymphoma (affecting the chest):

      • Breathing difficulties, fluid accumulation in the chest (pleural effusion), and possibly issues with the heart or veins (e.g., cranial vena cava syndrome).

      • Some dogs may also develop excessive thirst and urination due to high calcium levels (hypercalcemia).

    • Cutaneous lymphoma (affecting the skin):

      • Raised, ulcerated nodules or scaly, diffuse skin lesions, especially near the mucous membranes or lymph nodes.

    • Other signs:

      • If lymphoma affects other organs, signs may include blindness (eyes), seizures (CNS), kidney failure (renal), or pain due to bone involvement.

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Diagnosis
  • Physical Examination:

    • Enlarged, non-painful lymph nodes may suggest lymphoma.

  • Fine-Needle Aspiration (FNA):

    • A needle is used to take a sample from the swollen lymph nodes for cytologic (microscopic) examination.

    • Lymphoma typically shows a uniform population of abnormal lymphoid cells.

  • Biopsy and Histology:

    • A tissue sample can be examined under a microscope to determine the lymphoma’s type and grade (high or low).

  • Molecular Testing:

    • Flow Cytometry: Identifies lymphoma based on cell size and markers on the surface of the cells.

    • PCR (Polymerase Chain Reaction): Detects genetic markers to confirm lymphoma’s neoplastic (cancerous) origin.

  • Staging:

    • Staging helps determine how far the cancer has spread and guides treatment decisions.

    • Imaging and bone marrow evaluation may be needed to assess the extent of the disease.

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Treatment
  • Chemotherapy:

    • Systemic chemotherapy is the primary treatment and is effective for most types of lymphoma, achieving a high initial response rate (around 90%).

    • Common chemotherapy drugs include cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, and prednisone (CHOP protocol).

    • Lomustine, mitoxantrone, and rabacfosadine are other chemotherapy options.

    • The goal is to reduce symptoms and improve quality of life, as remission is often temporary (with relapses occurring in most cases).

    • Median survival time with chemotherapy is about 12 months for B-cell lymphoma and 6-8 months for T-cell lymphoma.

  • Radiotherapy:

    • Can be used in conjunction with chemotherapy, especially for localized tumors or specific organ involvement (e.g., mediastinal lymphoma or cutaneous lymphoma).

  • Prednisone:

    • Can help manage symptoms and may induce short-term remission (1-2 months). However, it is not curative and resistance can develop.

  • Autologous Bone Marrow Transplant:

    • A highly aggressive treatment that involves high-dose chemotherapy and the reinfusion of the dog's own bone marrow after it has been removed and treated. This is available at specialized centers.

  • Indolent (Low-Grade) Lymphoma:

    • These cases progress more slowly. Chlorambucil and prednisone are used for long-term management, and dogs can survive for over 2 years with treatment.

  • Surgical Resection:

    • For dogs with focal alimentary lymphoma (localized intestinal involvement), surgery to remove the tumor may be effective, followed by chemotherapy.

  • Other Options:

    • Verdinexor: A newer drug (FDA-approved for canine lymphoma in 2021) that may help in certain cases, though results have been less promising than traditional chemotherapy.

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Prognosis
  • Without treatment, dogs with lymphoma typically live only 4-6 weeks.

  • Chemotherapy can significantly improve the quality of life and extend survival, with some dogs living for a year or more.

  • The prognosis varies widely depending on lymphoma type, organ involvement, and response to treatment, with high-grade T-cell lymphoma generally having a poorer prognosis than B-cell lymphoma.

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​Leukemia

 
Etiology
  • Leukemia refers to the presence of cancerous (neoplastic) blood cells in the bone marrow or peripheral blood.

  • It’s rare in dogs (less than 10% of hematopoietic cancers) and more common in cats (15-35% of cases).

  • The exact causes of leukemia in animals are mostly unknown, but Feline Leukemia Virus (FeLV) is a known risk factor in cats.

  • There are no proven environmental or genetic causes identified for leukemia in small animals, although factors like toxins or immune dysfunction may play a role in some cases.

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Classification of Leukemia

Leukemia is classified based on:

  1. Cell type (lineage) – whether the leukemia involves lymphoid or myeloid cells.

  2. Clinical course – whether the leukemia is acute (fast-growing) or chronic (slow-growing).

  3. Cell differentiation – how mature the cancer cells are.

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Types of Leukemia
  • Lymphoproliferative Disorders:

    • Acute Lymphoblastic Leukemia (ALL) – aggressive, immature lymphoid cells.

    • Chronic Lymphocytic Leukemia (CLL) – slower, more differentiated lymphoid cells.

  • Myeloid Neoplasms:

    • Acute Myeloid Leukemia (AML) – fast-growing, often poorly differentiated cells.

    • Chronic Myeloproliferative Disorders – slower, more mature cells, including Chronic Myeloid Leukemia (CML), Polycythemia Vera, and Essential Thrombocythemia.

    • Myelodysplastic Syndromes (MDS) – a precursor to leukemia, with abnormal cells in the bone marrow but not yet fully cancerous.

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Clinical Signs
  • Chronic Leukemia (e.g., CLL):

    • Often asymptomatic for long periods.

    • If symptoms appear: mild lethargy, anorexia, weight loss, mild lymphadenopathy (swollen lymph nodes), and splenomegaly (enlarged spleen).

  • Acute Leukemia (e.g., ALL or AML):

    • More severe symptoms:

      • Prominent organ enlargement (e.g., spleen, liver, lymph nodes).

      • Hemorrhages (nosebleeds, bruising).

      • Neurological symptoms (seizures, weakness).

      • Fever and cytopenias (low blood cell counts) leading to weakness, infection, or anemia.

  • General Symptoms:

    • Dogs and cats may show systemic symptoms like lethargy, poor appetite, and weight loss.

    • Chronic leukemias tend to show milder signs, while acute forms progress rapidly and can be life-threatening.

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Diagnosis 
  • Blood Tests:

    • In many cases, leukemia can be diagnosed by finding a high number of neoplastic cells in the peripheral blood.

  • Bone Marrow Biopsy:

    • If blood tests don’t show conclusive results, a bone marrow biopsy is often needed. The presence of more than 30% blast cells in the marrow typically confirms acute myeloid leukemia (AML).

  • Cell Lineage Identification:

    • Special tests like cytochemistry, immunocytochemistry, and flow cytometry may be required to determine the exact type of leukemia.

    • Immunophenotyping markers (e.g., CD79a, CD3, CD11b) help identify the specific lineage of leukemia (whether it’s from lymphoid or myeloid cells).

  • Differential Diagnosis:

    • Leukemia can be confused with other conditions like lymphoma or myelodysplastic syndromes (MDS). Clonality tests may help in some cases but are not widely available.

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Treatment
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Acute Leukemia:

  • Aggressive Chemotherapy is needed to suppress the malignant cells and restore normal hematopoiesis (blood cell production).

    • CHOP protocol (cyclophosphamide, doxorubicin, vincristine, prednisone) is commonly used for acute lymphoblastic leukemia (ALL), although remission rates are typically less than 30%.

    • Supportive Care (e.g., antibiotics, fluids, blood transfusions) is also critical to manage complications like infections, anemia, or bleeding.

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Chronic Leukemia:

  • Chronic Lymphocytic Leukemia (CLL) is slower-growing and may not require immediate treatment unless there is significant organ enlargement, anemia, or other complications.

    • Chlorambucil (an oral chemotherapy drug) is the most commonly used treatment for CLL. It may be used alone or with prednisone for better results.

    • Complete remission is rare, but survival times can range from 1 to 3 years with good quality of life.

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Acute Myeloid Leukemia (AML):

  • AML generally has a poor response to therapy, and no standard protocol has been established. However, cytosine arabinoside combined with doxorubicin or cyclophosphamide is commonly used.

    • Maintenance therapy with a COAP protocol (cyclophosphamide, vincristine, cytosine arabinoside, prednisone) can be tried after remission.

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Chronic Myeloproliferative Disorders:

  • Hydroxyurea is often used to treat conditions like chronic myeloid leukemia (CML), essential thrombocythemia, and polycythemia vera.

  • Phlebotomy (removing excess blood) may also be used for polycythemia vera.

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Other Treatment Options:

  • Radiotherapy and immunotherapy are under investigation as alternative treatments.

  • Bone marrow transplantation may offer a curative option in certain cases, but this is still experimental.

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Prognosis
  • Acute Leukemia (especially ALL and AML) is usually fatal without aggressive treatment, with a poor overall prognosis due to the rapid progression of the disease.

  • Chronic Leukemia (like CLL) may allow dogs or cats to live for several years, especially if treated early and managed well.

  • Survival time varies greatly, but with treatment, CLL can be managed for 1-3 years, while AML generally has a much shorter survival rate.

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