Heme #6: AML, ALL, CML, CLL, MM

Question 1

What do myeloid cells give rise to?

What do lymphoid cells give rise to?

Answer 1

Myeloid: RBCs

Lymphoid: Lymphocytes (WBCs) and natural killer cells

Question 2

Acute Lymphocytic Leukemia
-MC childhood malignancy (peak is ages 2-5). Other risk factors are…
-Pathophysiology of this condition
-Symptoms as a result of

Answer 2

-RF: Boys, Down Syndrome, Ages 2-5
-Overpopulation of immature WBC’s (blasts) overtake normal hematopoeisis, resulting in pancytopenia
-Symptoms: fever and infections (leukopenia), bleeding from thrombocytopenia, petechiae, purpura, anemia, pallor, fatigue.
–CNS symptoms: stiff neck, visual changes, METs to CNS and testes MC.
–Hepatosplenomegaly, abdominal pain, LAD

Question 3

What is the MC physical exam finding of ALL?

What should you remember to remember this condition?

Answer 3

-Hepatomegaly or splenomegaly

ALL my children. MC childhood malignancy.

Question 4

Diagnostics for ALL
-CBC + peripheral smear
-Bone marrow aspiration
-What is the most accurate test to determine different types of leukemia?

Answer 4

-CBC: WBC 5,000 - 100,000, thrombocytopenia
-Bone marrow aspiration: hypercellular with > 20% blasts (DEFINITIVE)
-Flow cytometry test is the best way to distinguish subtypes of leukemia

Question 5

ALL is/isn’t highly response to combination chemotherapy?

If the patient has CNS disease, what medication can be used as treatment?

Answer 5

It is highly responsive to combination chemotherapy!

-Intrathecal Methotrexate

Question 6

What is tumor lysis syndrome?
-Remember, it is related to the leukemias.

Answer 6

-Emergency that occurs after treatment due to rapid tumor cell lysis after chemotherapy, resulting in potassium, phosphate, and nucleic acids into circulation

Question 7

-Symptoms of tumor lysis syndrome

-Lab findings with tumor lysis syndrome

Answer 7

-Symptoms: muscle cramps, tetany, nausea, vomiting, lethargy, HF, kidney injury

-Hypocalcemia
-Hyperuricemia, hyperphosphatemia, hyperkalemia, and acute kidney injury

Question 8

How do you treat tumor lysis syndrome?

How can you prevent tumor lysis syndrome with medication?

Answer 8

-Treat electrolyte abnormalities, IVF

-Rasburicase or Allopurinol (catalyzes uric acid to a stable compound)

Question 9

Chronic Lymphocytic Leukemia (CLL) is
-The MC form of leukemia in adults
-Mature B cell clonal malignancy
-Risk Factors?

Answer 9

-Increasing age (70 years is median age)
-Male gender

Question 10

CLL symptoms

Answer 10

-Usually asymptomatic
-Pancytopenia: anemia symptoms (pallor, fatigue MC, dyspnea), neutropenia (increased infections), and thrombocytopenia (mucocutaneous bleeding)

-Lymphadenopathy MC exam finding, Splenomegaly, skin lesions (leukemia cutis)

Question 11

What is seen on CBC with peripheral smear for CLL?

What other unique lab finding?

Answer 11

-Absolute lymphocytosis: small, well-differentiated normal-appearing lymphocytes with scattered “smudge cells”
–Smudge cells: fragile B cells become crushed by cover slip during slide preparation

-Hypogammaglobulinemia: increased incidence of autoimmune hemolytic anemia.

Question 12

Management for CLL

Answer 12

-Chemotherapy

-Allogeneic stem cell transplant curative

Question 13

Acute Myeloid Leukemia (AML)
-MC acute leukemia in adults
-Pathophysiology
-MC subtype

Answer 13

-Patho: accumulation of leukemia blasts (immature WBCs) in the bone marrow –> pancytopenia
-Acute promyelotic leukemia (APL or M3): associated with DIC, presence of Auer rods, and myeloperoxidase positivity

Question 14

Symptoms of AML

Answer 14

-Pancytopenia: anemia (general fatigue MC initial symptom), thrombocytopenia (bleeding), neutropenia (infections)

Question 15

What is seen on
-CBC with peripheral smear:
-Bone marrow biopsy (GOLD STANDARD):
-Immunophenotyping:

For AML

Answer 15

-CBC (best initial test): normocytic normochromic anemia. Thrombocytopenia. Circulating myeloblasts.

-Bone marrow biopsy (GOLD): >20% myeloblasts. Auer Rods (pink/red rods in cytoplasm) with APL.

-Immunophenotyping: Myeloperoxidase positivity with APL.

Question 16

Management for AML

Answer 16

-Combination chemotherapy
-Al-trans-retinoic acid added for M3**

Question 17

What is a leukostasis reaction (associated with AML and CML)?

Explain the pathophysiology of this.

What are symptoms/seen on diagnostics?

Answer 17

-Leukostasis leads to white cell plugs in microvasculature, impeding blood flow, causing local hypoxemia

-Hyperleukocytosis (WBC > 100,000) + symptoms due to tissue hypoxia (lung, CNS, heart, etc.)

Question 18

Management for a leukostasis reaction

Answer 18

-Leukapheresis (has rapid improvement): removes WBCs from the blood

Question 19

Chronic Myelogenous Leukemia (CML)
-What is it?
-Pathophysiology (two genes remember)
-Symptoms

Answer 19

-Uncontrolled production of mature and maturing granulocytes (predominantly neutrophils, but also basophils and eosinophils)

-Fusion of BCR (on chromosome 22) and ABL1 (on chromosome 9), resulting in BCR-ABL1 fusion gene. Translocation of 9 and 22 = Philadelphia chromosome.

-Symptoms: fatigue, night sweats, splenomegaly (MC), pruritus after hot showers/baths

Question 20

Diagnostics for CML
-CBC with peripheral smear:
-Leukocyte alkaline phosphatase score:
-Genetic testing for…

Answer 20

-CBC: leukocytosis with granulocytic cells (neutrophilia, basophilia, eosinophilia)

-LAP score decreased. LAP only found in functioning WBCs not leukemic cells.

Genetic testing for Philadelphia chromosome.

Question 21

Management for CML

Answer 21

-Tyrosine kinase inhibitors (Imatinib, Nilotinib, Dasatinib)

-Hematopoietic stem cell transplant most effective cure.

Question 22

Multiple Myeloma (Plasmacytoma)
-What is it
-MC primary bone malignancy in adults
-Pathophysiology

Answer 22

Cancer due to proliferation of single clone of plasma cells, leading to increased production of ineffective monoclonal antibodies (IgG, IgA, and IgM)

Plasma cells accumulate in the bone marrow, interrupting normal cell production –> kidney injury

Question 23

Symptoms of Multiple Myeloma
-Think BREAK your bones

Answer 23

B: Bone pain (MC): Vertebral MC, ribs. Pathologic fractures, osteolytic lesions, radiculopathy
R: Recurrent infections (ineffective IgG)
E: Elevated calcium (bone destruction)
A: Anemia (fatigue, pallor, weight loss)
K: kidney injury (increased BUN and Cr)

Question 24

Diagnostics for Multiple Myeloma
-Serum protein electrophoresis
-Urine protein electrophoresis
-CBC
-Skull radiographs
-Bone marrow aspiration (definitive)

Answer 24

-Protein: monoclonal protein spike: IgG MC
-Urine: Bence-Jones protein (kappa or lambda chains)
-CBC: Rouleaux formation (RBCs with stack of coins appearance)
-Skull xrays: punched out, lytic lesions.
-Bone marrow: plasmacytosis > 10%

Question 25

Treatment for Multiple Myeloma

Answer 25

-Autologous stem cell transplant most effective
–Chemotherapy is a temporary fix for symptoms