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A Review of Leukemias for the Physician Assistant Exam

Leukemias are high levels of abnormal white cells that overwhelm and overtake the bone marrow. For Physician Assistant Exam (PANCE) purposes, be familiar with four types of leukemias — two acute leukemias and two chronic leukemias. The acutes are acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). They can invade and take over other organs. The chronic forms are chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL).

Try to pick up on key points that differentiate the leukemias from each other. For example, Auer rods (needle-shaped, lysosomal-like material within the cytoplasm of the leukemic cell) are a key finding in AML, and the Philadelphia chromosome is important for diagnosing CML. This type of hematologic minutiae is high yield for test questions.

Acute lymphocytic leukemia

Acute lymphocytic leukemia (ALL) is a condition primarily of childhood and young adulthood, although it can also occur in older adults. The cell line affected in ALL is the lymphoblast, whereas acute myeloid leukemia (AML) affects the myeloblast. Here are some key points concerning ALL:

  • Risk factors of acquiring ALL include having Down syndrome and perhaps radiation exposure. The risk due to other toxic exposures is uncertain.

  • Clinical presentation can include type B constitutional symptoms, including fevers, chills, drenching night sweats, and weight loss as well as easy bleeding and bruising.

  • On physical examination, lymphadenopathy and hepatosplenomegaly can be present.

  • Initial labs can show a significant leukocytosis with blasts. Anemia and thrombocytopenia can be present.

  • In someone with ALL, do a chest radiograph to make sure that there’s no mediastinal mass.

  • Treatments include chemotherapy and bone marrow transplant.

People with ALL can test positive for terminal deoxynucleotidyl transferase (TDD). Common acute lymphoblastic leukemia antigen is expressed by most types of lymphoblastic leukemias. You may see either of these on the PANCE.

Acute myeloid leukemia

Acute myeloid leukemia (AML) is a very bad disease that can present either insidiously or abruptly. Different types of AML exist. One classification system, the French-American-British (FAB), has seven different types of AML.

Having a high clinical suspicion is the key to recognizing leukemia. Here are the key points you need to know about AML:

  • Risk factors include a history of benzene exposure.

  • Chromosomal aberrations such as Down syndrome and Klinefelter’s syndrome increase the risk of developing AML. Anti-cancer medications also can increase the risk of developing AML.

  • Clinical presentation can include bruising and bleeding and type B constitutional symptoms, including fever, weight loss, and overwhelming fatigue.

  • On physical examination, lymphadenopathy, petechiae, and splenomegaly can be present. A small percentage of people present with retinal bleeding.

  • Initial labs can show a significant leukocytosis with blasts or leukopenia. Anemia and thrombocytopenia can be profound.

  • The treatment is high-dose chemotherapy.

On a bone marrow aspirate of someone with AML, you can see Auer rods. You see Auer rods in certain forms of myelodysplasia as well.

When treating leukemias or high-grade lymphomas with chemotherapy, a potential complication is tumor lysis syndrome (TLS). Before giving chemo, give prophylaxis with intravenous fluids with bicarbonate to alkalinize the urine (with the goal of getting urine pH above 6.5) and with allopurinol to reduce hyperuricemia. In a condition called spontaneous tumor lysis syndrome, TLS occurs in the absence of chemotherapy.

Retinoic acid syndrome is a reaction to the medication tretinoin, which is used to treat a form of AML called acute promyelocytic leukemia. It’s high yield for tests because it can cause a unique syndrome that presents with an ARDS-like picture, including hypoxemia and opacification of both lung fields. The treatment is supportive and intravenous steroids. Other immunosuppressive medications may be given.

Chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia you’ll encounter. You usually see CLL in the older population. The first indication of CLL is often an abnormality of blood work, specifically an elevated white count with a significant lymphocytosis. Here are the main points about CLL concerning the Rai staging of classification for CLL:

  • Stage 0: You see an isolated lymphocytosis.

  • Stage I: Lymphadenopathy is present.

  • Stage II: You see splenomegaly.

  • Stage III: Anemia is present.

  • Stage IV: You see thrombocytopenia.

CLL often follows an indolent course, although it does have the potential for malignant transformation. Usually chemotherapy is indicated for Stage II or above unless significant adenopathy is present.

The preferred treatment for CLL is now imatinib (Gleevec). Other treatment options include a bone marrow transplant.

Chronic myelogenous leukemia (CML)

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, peaks in incidence for people in their mid 40s. Testing for the Philadelphia chromosome, which is a translocation between chromosomes 9 and 22, is highly indicative that CML may be present. Philadelphia chromosome is associated with a BCR/ABL fusion protein.

  • Risk factors of CML include smoking and perhaps high doses of radiation.

  • Clinical presentation can include type B constitutional symptoms, fatigue, and abdominal discomfort because of a large spleen. If the platelet or white cell counts are high enough, people can have related problems, including strokes, visual problems, lung problems, and heart problems (including MIs).

  • On physical examination, lymphadenopathy and splenomegaly can be present. Sometimes you can detect hepatomegaly on physical examination as well.

  • The lab pattern of CML is leukocytosis, thrombocytosis, high B12 levels, high uric acid levels, high LDH levels, and low leukocyte alkaline phosphatase.

  • The only CML treatment that has any shot at a cure is stem cell transplantation. Sometimes the medication imatinib (Gleevec) is used to help manage the disease process.

Hairy cell leukemia (HCL)

In a subtype of leukemia called hairy cell leukemia (HCL), blood cells actually look like hair when seen under a microscope. This condition has nothing to do with the hairiness of the individual. HCL is a disorder of B cells. The patient can have pancytopenia, and yes, splenomegaly. The treatment is 2-chlorodeoxyadenosine (2CDA).

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