clin med 2 test 1: heme malignancy ppt
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Questions and Answers

What is the definition of cancer?

  • Controlled cell growth with loss of apoptosis
  • Uncontrolled cell growth with gain of apoptosis
  • Controlled cell growth with gain of apoptosis
  • Uncontrolled cell growth with loss of apoptosis (correct)

    • What type of cancer occurs when cancer originates from a blood cell?

  • Leukemia or Lymphoma (correct)
  • Melanoma
  • Myeloma
  • Carcoma

    • What is the origin of Myeloma?

  • From T cells
  • From Neutrophils
  • From Monocytes
  • From plasma cells, a type of B cell (correct)

    • What is the normal maturation sequence of a Neutrophil?

    <p>Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band → Neutrophil</p> Signup and view all the answers

    What is a risk factor for developing Acute Leukemias?

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

    What is a characteristic of Chronic Leukemias?

    <p>Exposure to ionizing radiation is a risk factor</p> Signup and view all the answers

    What is a risk factor for developing Lymphomas?

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

    What is a characteristic of Multiple Myeloma?

    <p>Higher incidence in African Americans</p> Signup and view all the answers

    What is the type of leukemia that occurs when there is a neoplastic transformation of a B cell?

    <p>Myeloma</p> Signup and view all the answers

    Which of the following is a risk factor for developing Acute Erythroid Leukemia?

    <p>Down Syndrome</p> Signup and view all the answers

    What is the name of the genetic translocation that causes Chronic Myeloid Leukemia?

    <p>t(9;22)</p> Signup and view all the answers

    Which of the following is a characteristic of Multiple Myeloma?

    <p>It affects multiple parts of the body</p> Signup and view all the answers

    What is the name of the syndrome that is a pre-malignancy of the bone marrow?

    <p>Myelodysplastic Syndrome</p> Signup and view all the answers

    Which of the following is a risk factor for developing Lymphomas?

    <p>Immunosuppression</p> Signup and view all the answers

    What is the relationship between relatives of probands and the risk of developing Lymphomas?

    <p>Relatives of probands have a 3.5x higher chance of developing Lymphomas</p> Signup and view all the answers

    What is the association between Body Mass Index and the risk of developing Multiple Myeloma?

    <p>There is a positive association between Body Mass Index and the risk of developing Multiple Myeloma</p> Signup and view all the answers

    What is the typical outcome for patients with acute leukemia if left untreated?

    <p>Death in a matter of hours, days, or weeks</p> Signup and view all the answers

    What is a critical aspect of diagnosing acute leukemia?

    <p>Recognizing the presence of blasts in the peripheral blood</p> Signup and view all the answers

    What is the most common acute leukemia in adults?

    <p>Acute Myeloid Leukemia (AML)</p> Signup and view all the answers

    What is a common symptom of anemia in patients with acute leukemia?

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

    What is a rare but possible complication of acute leukemia?

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

    What is a common risk factor for developing acute leukemia?

    <p>Exposure to chemotherapy or radiation therapy</p> Signup and view all the answers

    What is a common laboratory finding in patients with acute leukemia?

    <p>High white blood cell count</p> Signup and view all the answers

    What is a common mistake to make when evaluating a patient with suspected acute leukemia?

    <p>Assuming a low WBC count rules out leukemia</p> Signup and view all the answers

    What is the primary reason Acute Leukemia is so dangerous?

    <p>The leukemic blasts take over the bone marrow entirely and do not allow normal growth and production of normal WBC's, RBC's and Platelets.</p> Signup and view all the answers

    When is it necessary to immediately contact an on-call hematologist?

    <p>When seeing 'blasts' in the WBC differential.</p> Signup and view all the answers

    What is a common symptom of hyperviscosity in Acute Leukemia?

    <p>Changes in mentation and vision.</p> Signup and view all the answers

    What is the general treatment for Acute Leukemia?

    <p>Chemotherapy, unless palliative care is chosen.</p> Signup and view all the answers

    What is the term for the specific treatment regimen in AML?

    <p>'7 + 3'</p> Signup and view all the answers

    What is the special treatment required for Acute Promyelocytic Leukemia (APML)?

    <p>Immediate ATRA administration.</p> Signup and view all the answers

    What is the term for the specific diagnostic feature of Acute Promyelocytic Leukemia (APML)?

    <p>Auer Rods.</p> Signup and view all the answers

    What is the term for the type of immunotherapy used in advanced treatments?

    <p>CAR-T therapy.</p> Signup and view all the answers

    What is a common side effect of CAR-T therapy?

    <p>Cytokine Release Syndrome (CRS).</p> Signup and view all the answers

    What is the long-term side effect of CAR-T therapy?

    <p>B cell aplasia leading to hypogammaglobulinemia and cytopenia.</p> Signup and view all the answers

    What is a characteristic of Chronic Myeloid Leukemia (CML)?

    <p>Elevated WBC and often high plt count with almost normal Hb</p> Signup and view all the answers

    What is a common feature of Chronic Lymphocytic Leukemia (CLL)?

    <p>Elevated WBC count, often in the hundreds of thousands</p> Signup and view all the answers

    What is a treatment option for Chronic Myeloid Leukemia (CML)?

    <p>Imatinib, a tyrosine kinase inhibitor</p> Signup and view all the answers

    What is a complication of Chronic Lymphocytic Leukemia (CLL)?

    <p>Increased risk of infections</p> Signup and view all the answers

    What is a symptom of splenomegaly in Chronic Myeloid Leukemia (CML)?

    <p>Feeling full when eating a very small meal</p> Signup and view all the answers

    What is the typical age range for peak incidence of Hodgkin Lymphoma?

    <p>20-24 and 80-84</p> Signup and view all the answers

    What is the primary indication for EXCISIONAL biopsy in Non-Hodgkin Lymphoma?

    <p>Examining the architecture of the lymph node</p> Signup and view all the answers

    What is the mechanism of action of Rituximab in treating B cell Non-Hodgkin Lymphoma?

    <p>Optimizing B cells for antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity</p> Signup and view all the answers

    What is the annual progression rate from MGUS to Multiple Myeloma?

    <p>1%/year</p> Signup and view all the answers

    What is the primary complication of Hypercalcemia in Multiple Myeloma?

    <p>Bone lesions with pathological fractures</p> Signup and view all the answers

    What is the common laboratory finding in patients with acute leukemia?

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

    What is the term for the specific treatment regimen in Acute Myeloid Leukemia (AML)?

    <p>7+3</p> Signup and view all the answers

    What is the common side effect of CAR-T therapy?

    <p>Cytokine Release Syndrome</p> Signup and view all the answers

    What is the primary characteristic of 'Owl Eye cells' in Hodgkin Lymphoma?

    <p>Tumor cells with a Reed-Sternberg appearance</p> Signup and view all the answers

    What is the most common age range for the peak incidence of Non-Hodgkin Lymphoma?

    <p>All ages, with no specific peak incidence</p> Signup and view all the answers

    What is the primary mechanism of action of Rituximab in treating B cell Non-Hodgkin Lymphoma?

    <p>Optimization of B cells for Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity</p> Signup and view all the answers

    What is the primary complication of Hypercalcemia in Multiple Myeloma?

    <p>Renal failure</p> Signup and view all the answers

    What is the annual progression rate from MGUS to Multiple Myeloma?

    <p>1%/year</p> Signup and view all the answers

    What is the primary indication for EXCISIONAL biopsy in Non-Hodgkin Lymphoma?

    <p>To examine the architecture of the lymph node</p> Signup and view all the answers

    What is the primary treatment option for patients with Multiple Myeloma?

    <p>BMT and/or CART therapy</p> Signup and view all the answers

    What is the primary characteristic of Waldenstrom Macroglobulinemia?

    <p>A type of Plasma Cell Dyscrasia</p> Signup and view all the answers

    What is the characteristic of Acute Myeloid Leukemia (AML)?

    <p>Severe and sudden with &gt;20% blasts</p> Signup and view all the answers

    Which type of cancer is associated with the 'Owl eyes' characteristic?

    <p>Hodgkin Lymphoma</p> Signup and view all the answers

    What is the typical age range for the peak incidence of Chronic Lymphocytic Leukemia (CLL)?

    <p>Older adults</p> Signup and view all the answers

    What is the characteristic of Multiple Myeloma?

    <p>Mid-thoracic back pain not alleviated when lying down</p> Signup and view all the answers

    What is the characteristic of Myelodysplastic Syndrome (MDS)?

    <p>A pre-cancer that will become cancer if left untreated</p> Signup and view all the answers

    Study Notes

    Cancer Generalities

    • Cancer is characterized by uncontrolled cell growth and loss of apoptosis (programmed cell death)
    • Can occur in any cell in the body
    • Cancer originating from a blood cell can be classified as Leukemia (myeloid or lymphoid), Lymphoma (lymphoid tissue), or Myeloma (plasma cells, a type of B cell)

    Blood Cell Types and Associated Cancers

    • Neutrophils → Acute Myeloid Leukemia
    • Lymphocytes → Acute Lymphocytic Leukemia
    • Monocytes → Acute Myeloid Leukemia
    • Eosinophils → Hypereosinophilic Syndrome
    • Basophils → AML, seen in CML and HD
    • RBC’s → Acute Erythroid Leukemia (rare)
    • Platelets → Acute Megakaryoblastic Leukemia (rare)

    Normal Neutrophil Development

    • Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band → Neutrophil

    Epidemiology of Acute Leukemias

    • Typically affects older people, non-Hispanic whites
    • Genetic disorders: Down Syndrome, Ataxia telangiectasia, Fanconi Anemia, Li Fraumeni
    • Radiation exposure
    • Chemical exposure

    Epidemiology of Chronic Leukemias

    • Ionizing radiation is the only known risk factor
    • CML was the first disorder proven to be caused by a genetic translocation [t(9;22)]

    Epidemiology of Lymphomas

    • Relatives of probands have a 3.5x higher chance of developing lymphoma
    • Higher incidence in patients with RA, hemolytic anemia, psoriasis, SLE, Systemic sclerosis, Polyarteritis nodosa, sarcoidosis, Crohn Disease, motor neuron disease, and Celiac disease
    • Immunosuppression
    • Viral infections (HIV, HTLV, EBV)

    Epidemiology of Multiple Myeloma

    • Higher incidence in African Americans
    • Risk increases with Body Mass Index
    • Association with Agent Orange exposure (especially those with MGUS)
    • Higher incidence in families (3.5x higher with 1st degree relative)

    Myelodysplastic Syndrome (MDS)

    • Not a malignancy, but a pre-malignancy of the bone marrow
    • Defined as...

    Cancer Generalities

    • Cancer is characterized by uncontrolled cell growth and loss of apoptosis (programmed cell death)
    • Can occur in any cell in the body
    • Cancer originating from a blood cell can be classified as Leukemia (myeloid or lymphoid), Lymphoma (lymphoid tissue), or Myeloma (plasma cells, a type of B cell)

    Blood Cell Types and Associated Cancers

    • Neutrophils → Acute Myeloid Leukemia
    • Lymphocytes → Acute Lymphocytic Leukemia
    • Monocytes → Acute Myeloid Leukemia
    • Eosinophils → Hypereosinophilic Syndrome
    • Basophils → AML, seen in CML and HD
    • RBC’s → Acute Erythroid Leukemia (rare)
    • Platelets → Acute Megakaryoblastic Leukemia (rare)

    Normal Neutrophil Development

    • Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band → Neutrophil

    Epidemiology of Acute Leukemias

    • Typically affects older people, non-Hispanic whites
    • Genetic disorders: Down Syndrome, Ataxia telangiectasia, Fanconi Anemia, Li Fraumeni
    • Radiation exposure
    • Chemical exposure

    Epidemiology of Chronic Leukemias

    • Ionizing radiation is the only known risk factor
    • CML was the first disorder proven to be caused by a genetic translocation [t(9;22)]

    Epidemiology of Lymphomas

    • Relatives of probands have a 3.5x higher chance of developing lymphoma
    • Higher incidence in patients with RA, hemolytic anemia, psoriasis, SLE, Systemic sclerosis, Polyarteritis nodosa, sarcoidosis, Crohn Disease, motor neuron disease, and Celiac disease
    • Immunosuppression
    • Viral infections (HIV, HTLV, EBV)

    Epidemiology of Multiple Myeloma

    • Higher incidence in African Americans
    • Risk increases with Body Mass Index
    • Association with Agent Orange exposure (especially those with MGUS)
    • Higher incidence in families (3.5x higher with 1st degree relative)

    Myelodysplastic Syndrome (MDS)

    • Not a malignancy, but a pre-malignancy of the bone marrow
    • Defined as...

    Acute Leukemias

    • Without treatment, acute leukemias are fatal, and death can occur within hours, days, or weeks
    • Acute leukemias are the most dangerous malignancies, requiring immediate referral to a hematologist without delay
    • These patients are the sickest in the hospital, and prompt identification of findings is crucial

    Signs and Symptoms of Acute Leukemia

    • CBC with "BLAST" in the differential, which is never normal in peripheral blood
    • Severe fatigue associated with anemia, cardiac damage, SOB, liver enzyme elevation, and renal insufficiency
    • High white cell count (>50-100K), which may require leukapheresis to reduce leukostasis

    Epidemiology of Acute Leukemia

    • AML is the most common acute leukemia in adults, while ALL is the most common in children
    • Incidence increases with age, with a median age of 65 years old
    • Incidence is similar between races
    • Almost all cases are associated with acquired gene mutations, with unknown underlying causes
    • Environmental factors like exposure to chemotherapy, RT, chemicals, benzene exposure, and smoking are contributing factors
    • Germline mutations, Trisomy 21, Fanconi's anemia, and CHIP (Clonal Hematopoiesis of Indeterminate Significance) are also associated with acute leukemia

    Clinical Presentation of Acute Leukemia

    • Anemia
    • Fevers
    • Bleeding/bruising or DIC
    • Bone/Joint pains
    • Skin manifestations
    • Pallor
    • Petechiae
    • Ecchymosis
    • Rare: gingival hyperplasia (monocytic), oral candida, herpetic lesions
    • CNS involvement: confusions, CNS hemorrhage, meningitis (monocytic)
    • Hepatomegaly and splenomegaly (10%), usually indicating ALL or prior MPN
    • Metabolic/electrolyte abnormalities:
      • Hyperphosphatemia
      • Hypocalcemia
      • High uric acid
      • Hyperkalemia
      • High LDH

    Why Acute Leukemia is so Dangerous

    • Acute Leukemia cells are "sticky," causing blockages in capillaries and vasculature, leading to infarctions in organs
    • Leukemic blasts take over the bone marrow, preventing normal growth and production of WBCs, RBCs, and platelets
    • Doubling time for malignant cells can be hours, allowing them to quickly take over the entire marrow space

    When to Suspect Acute Leukemia

    • When "blasts" are seen in the WBC differential, immediately contact a hematologist
    • Sudden changes in WBC count can indicate leukemia or infection and medication use
    • WBC count elevation may require discussion with a specialist, especially if there are signs of hyperviscosity:
      • Changes in mentation and vision
      • Bleeding from gums or increased spontaneous bruising
      • Chest pains
      • Renal failure (from TLS!)
      • Shortness of breath
      • Chest pains

    Treatments for AML/ALL

    • Treatment of acute leukemia always involves chemotherapy (unless palliative care)
    • Cytoreduction may be necessary, using Hydroxyurea (in AML) or steroids (in ALL), and Leukopheresis
    • Fit patients will need to undergo chemotherapy:
      • AML: "7 + 3" (High dose Ara C plus anthracycline)
      • ALL: Chemotherapies with steroids as the backbone, depending on age and type of lymphocyte (B or T cell)
    • Many patients will require a CONSOLIDATION BONE MARRROW TRANSPLANT after achieving remission
    • CAR-T therapy is now used in some leukemias
    • Not everyone will be eligible for chemotherapy treatment, and many will not be eligible for bone marrow transplant
    • Supportive care is offered for those who are not eligible for intensive chemotherapy

    Special Case of AML: Acute Promyelocytic Leukemia (APML) aka M3

    • Has the special t (15;17), Retinoid Acid Receptor Alpha (RAR-A)
    • Presents with DIC and will die of bleeding complications if not found early
    • MUST START ATRA IMMEDIATELY IF SUSPECTED until confirmation tests return
    • Auer Rods are needlelike crystals diagnostic of APML
    • APML has an EXCELLENT prognosis but a difficult initial course

    Advanced Treatments

    • Bone Marrow Transplant
    • Chimeric Antigen Receptor T cell (CART) therapy:
      • Type of immunotherapy
      • FDA approved for B-ALL, B-NHL, Mantle Cell Lymphoma, follicular Lymphoma, and Multiple Myeloma
      • Some good results, especially in B-ALL with CR 70-94%, but some will relapse regardless of initial response
      • Major side effects: Fever, Cytokine Release Syndrome (CRS), and long-term B cell aplasia leading to hypogammaglobulinemia and cytopenia

    Chronic Leukemia Types

    • Chronic Myeloid Leukemia (CML) is characterized by the presence of the BCR-ABL translocation t(9;22).
    • CML is often associated with elevated White Blood Cell (WBC) count, potentially high Platelet (PLT) count, and almost normal Hemoglobin (Hb) levels.
    • Splenomegaly is always present in CML.
    • Tyrosine kinase inhibitors are used to treat CML.
    • CML can progress to an accelerated phase (with 30% blasts) which is treated similarly to Acute Myeloid Leukemia (AML).

    Chronic Lymphocytic Leukemia (CLL)

    • CLL is characterized by a VERY elevated WBC count (in the hundreds of thousands).
    • The Complete Blood Count (CBC) report often includes the presence of "smudge cells".
    • New treatments for CLL involve oral medications.
    • Depending on the disease stage, patients with CLL can have a normal life expectancy.

    Chronic Leukemias General Characteristics

    • Chronic Leukemias are not usually emergencies and can be managed over a long period.
    • Patients are at increased risk of infections, especially in CLL, which may be mitigated by monthly IVIG infusions.
    • Splenomegaly in CML can lead to feelings of fullness even when eating small meals.

    Treatment of Chronic Leukemias

    • Imatinib was the first Tyrosine Kinase Inhibitor (TKI) approved for CML treatment.
    • Historically, CLL treatment involved chemotherapy, but new oral medications are now available.

    Lymphomas

    • Hodgkin Lymphoma (HL) presentation: lymphadenopathy, fatigue, pruritus, with peak ages at 20-24 and 80-84 years old
    • HL treatment: complex chemotherapy, radiation therapy, or a combination of both, with bone marrow transplantation (BMT) and CART therapy as options
    • "Owl Eye cells" are associated with HL

    Non-Hodgkin Lymphoma (NHL)

    • Affects all races, ages, and socioeconomic strata, with increased risk for those exposed to chemicals, radiation, HIV, EBV, and with breast implants
    • Presentation: lymphadenopathy, fever of unknown origin, and possible association with autoimmune disorders, immunodeficiencies, and H. pylori infection
    • Physical exam: enlarged lymph nodes (LN), spleen, and CNS involvement
    • Diagnosis: requires excisional biopsy of LN (FNA's are poor), with examination of CBC, renal function, and uric acid levels
    • Treatment: depends on NHL type, with options including radiation, chemotherapy, immunomodulators, and BMT/CART

    Rituximab

    • Monoclonal Ab against CD20 Ag, optimizing B cells for Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity
    • Used in B cell (CD 20+) Lymphomas, commonly with R-CHOP/CHOP or R-EPOCH chemotherapy regimens

    Plasma Cell Dyscrasias

    • MGUS: 1%/year progression rate to multiple myeloma
    • Smoldering myeloma and multiple myeloma are complications of MGUS
    • Waldenström macroglobulinemia: a type of lymphoma
    • Amyloidosis: a complication of plasma cell dyscrasias
    • CRAB Criteria: calcium elevation, renal failure, anemia, bone lesions
    • Pitfalls of MM: worsening anemia, renal failure, hypercalcemia, and increased thirst and urination frequency
    • Bone lesions with pathological fractures are common in MM
    • When to refer a patient: anemia with renal insufficiency +/- hypercalcemia, or lytic lesions on imaging

    Multiple Myeloma (MM) Management

    • Oncologist risk stratification and assessment for autologous transplant
    • Stem cell collection after 3-6 months of induction chemotherapy, which can be kept for many years
    • Auto transplant prolongs the time to first relapse, but MM is not curable with auto transplant; it only prolongs survival
    • Treatment aims to improve quality of life and manage symptoms, but there is no current cure for MM

    Lymphomas

    • Hodgkin Lymphoma (HL) presentation: lymphadenopathy, fatigue, pruritus, with peak ages at 20-24 and 80-84 years old
    • HL treatment: complex chemotherapy, radiation therapy, or a combination of both, with bone marrow transplantation (BMT) and CART therapy as options
    • "Owl Eye cells" are associated with HL

    Non-Hodgkin Lymphoma (NHL)

    • Affects all races, ages, and socioeconomic strata, with increased risk for those exposed to chemicals, radiation, HIV, EBV, and with breast implants
    • Presentation: lymphadenopathy, fever of unknown origin, and possible association with autoimmune disorders, immunodeficiencies, and H. pylori infection
    • Physical exam: enlarged lymph nodes (LN), spleen, and CNS involvement
    • Diagnosis: requires excisional biopsy of LN (FNA's are poor), with examination of CBC, renal function, and uric acid levels
    • Treatment: depends on NHL type, with options including radiation, chemotherapy, immunomodulators, and BMT/CART

    Rituximab

    • Monoclonal Ab against CD20 Ag, optimizing B cells for Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity
    • Used in B cell (CD 20+) Lymphomas, commonly with R-CHOP/CHOP or R-EPOCH chemotherapy regimens

    Plasma Cell Dyscrasias

    • MGUS: 1%/year progression rate to multiple myeloma
    • Smoldering myeloma and multiple myeloma are complications of MGUS
    • Waldenström macroglobulinemia: a type of lymphoma
    • Amyloidosis: a complication of plasma cell dyscrasias
    • CRAB Criteria: calcium elevation, renal failure, anemia, bone lesions
    • Pitfalls of MM: worsening anemia, renal failure, hypercalcemia, and increased thirst and urination frequency
    • Bone lesions with pathological fractures are common in MM
    • When to refer a patient: anemia with renal insufficiency +/- hypercalcemia, or lytic lesions on imaging

    Multiple Myeloma (MM) Management

    • Oncologist risk stratification and assessment for autologous transplant
    • Stem cell collection after 3-6 months of induction chemotherapy, which can be kept for many years
    • Auto transplant prolongs the time to first relapse, but MM is not curable with auto transplant; it only prolongs survival
    • Treatment aims to improve quality of life and manage symptoms, but there is no current cure for MM

    Myeloid Leukemias

    • Acute Myeloid Leukemia (AML): sudden onset, >20% blasts, severe
    • Chronic Myeloid Leukemia (CML): characterized by Philadelphia chromosome

    Lymphoid Leukemias

    • Acute Lymphoblastic Leukemia (ALL): typically affects kids
    • Chronic Lymphocytic Leukemia (CLL): typically affects older adults, characterized by smudge cells

    Lymphomas

    Hodgkin's Lymphoma

    • Peaks in young age and old age
    • Characterized by "owl eyes" and Reed-Sternberg cells

    Non-Hodgkin's Lymphoma

    • Affects all ages and races
    • Characterized by splenomegaly and implants
    • Associated with H. pylori

    Multiple Myeloma

    • Presents with mild back pain, typically in the mid-thoracic region
    • Pain not alleviated when lying down
    • Affects middle-aged individuals
    • Can cause cord suppression when lying in a supine position

    Myelodysplastic Syndrome (MDS)

    • A premalignant disorder that will progress to cancer if left untreated
    • A precursor to cancer

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    Learn about the characteristics of cancer and how it can occur in different blood cell types, leading to various types of leukemia and lymphoma.

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