Section 3: Leukemias, Myeloproliferative Disorders, Plasma Cell Disorders, Lymphoma

Question 1

Best initial test in acute leukemia

Answer 1

Peripheral smears showing blasts

Question 2

Rx for patients with acute leukemia with poor prognosis

Answer 2

Bone marrow transplantation should be performed as soon as chemotherapy induces remission

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5300-5317). Kaplan Publishing. Kindle Edition.

Question 3

Diagnosis in leukemia:

• Auer rods
• DIC

Answer 3

• Acute myeloid leukemia (AML)
• M3, acute promyelocytic leukemia

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5300-5317). Kaplan Publishing. Kindle Edition.

Question 4

Rx of leukemia

Answer 4

Chemotherapy with idarubicin (or daunorubicin) and cytosine arabinoside is the best initial therapy for acute myelogenous leukemia

Add all-trans-retinoic-acid (ATRA) to the treatment of M3 (acute promyelocytic) leukemia

Add intrathecal methotrexate for acute lymphocytic leukemia (ALL)

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5300-5317). Kaplan Publishing. Kindle Edition.

Question 5

A patient presents with shortness of breath, confusion, and blurry vision. His white cell count is over 100,000. What is the best initial therapy?

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5300-5317). Kaplan Publishing. Kindle Edition.

Answer 5

Acute leukemia can sometimes present with an extremely high white cell count. When the count goes above 100,000, these cells result in sludging of the blood vessels of the brain, eyes, and lungs. Chronic lymphocytic leukemia rarely does this, because lymphocytes are much smaller and do not occlude vessels. Leukostasis is treated with leukapheresis, which removes white cells via centrifugation of blood. Hydroxyurea is also added to lower the white cell count.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5300-5317). Kaplan Publishing. Kindle Edition.

Question 6

Lab features of myelodysplasias

Answer 6

Pancytopenia

Elevated MCV

Low reticulocyte count

Macroovalocytes

There is a special neutrophil with 2 lobes called a “Pelger-Huet cell.”

Normal B12 level

There will be a small number of blasts but not enough to be considered acute leukemia

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5319-5329). Kaplan Publishing. Kindle Edition.

Question 7

Rx of Myelodysplasias (MDS)

1. Major Rx modality
2. Specific therapy
3. Rx for those with 5q minus syndrome

Answer 7

1. Treatment is largely supportive with transfusions as needed.
2. Azacitadine is a specific therapy for myelodysplasia (MDS).
3. Those with the 5q minus syndrome are treated with lenalidomide.Lenalidomide has tremendous efficacy in decreasing transfusion dependence in MDS.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5319-5329). Kaplan Publishing. Kindle Edition.

Question 8

Chronic Myelogenous Leukemia (CML)

Look for an elevated white cell count that is predominantly neutrophils. Splenomegaly is frequent

Best initial test

Most accurate test

The best initial therapy

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5333-5341). Kaplan Publishing. Kindle Edition.

Answer 8

Leukocyte alkaline phosphatase (LAP) score. An elevated neutrophils count with a low LAP score is CML. Reactive high white counts from infection give an elevated LAP score. LAP is up in normal cells, not CML

Most accurate test: Philadelphia chromosome

Imatinib (Gleevec)

Bone marrow transplantation is the only way to cure CML, but this is never the best initial therapy, because imatinib leads to 90 percent hematologic remission with no major adverse effects.

Dasatinib and nilotinib are tyrosine kinase inhibitors. They can be used as first-line therapy or as an alternative in those not responding to imatinib.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5341-5350). Kaplan Publishing. Kindle Edition.

Question 9

True or False: The following drugs are useful in CML

• Inteferon
• Hydroxyurea
• Bulsufan

Answer 9

• Interferon: Much less efficacy; causes uncomfortable, flulike symptoms
• Hydroxyurea: Never makes the Philadelphia chromosome negative
• Bulsulfan: Never for anything except the exam ask which drug causes pulmonary fibrosis

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5341-5350). Kaplan Publishing. Kindle Edition.

Question 10

Best inital test in CLL

Answer 10

Peripheral blood smear shows “smudge” cells, which are ruptured nuclei of lymphocytes.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5358-5359). Kaplan Publishing. Kindle Edition.

Question 11

Rx of CLL

1. In asymptomatic patients
2. In more advanced disease
3. Which therapy is most likely to extend survival (in advanced disease)?
4. Name the anti-CD52 agent used for CLL that is better than chlorambucil

Answer 11

1. No Rx
2. Fludarabine combined with rituximab. Chlorambucil is not as effective
3. Fludarabine
4. Alemtuzumab

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5364-5367). Kaplan Publishing. Kindle Edition.

Question 12

Hairy Cell Leukemia

Presents with the following:

• Pancytopenia
• Massive splenomegaly
• Middle-aged patient (50s)

The most accurate test

The best initial therapy

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5372-5380). Kaplan Publishing. Kindle Edition.

Answer 12

Tartrate resistant acid phosphatase (TRAP), smear showing hairy cells

Cladribine (2-CDA)

Cladribine is a purine analog (subclass of antimetabolites). The major toxicity is bone marrow

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5372-5380). Kaplan Publishing. Kindle Edition.

Question 13

Myelofibrosis Presents in the same way as hairy cell leukemia (pancytopenia and splenomegaly) with a normal TRAP level.

What is the key to diagnosis?

Answer 13

A key feature is teardrop-shaped cells on the smear.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5372-5380). Kaplan Publishing. Kindle Edition.

Question 14

Pvera

Diagnostic tests to do in CCS

Answer 14

• CBC
• Arterial blood gas to exclude hypoxia as a cause of erythrocytosis
• Leukocyte alkaline phosphatase (LAP)
• Erythropoietin level (low)
• Hematology consultation
• Nuclear red cell mass test
• JAK2 mutation test

The B12 and LAP levels are elevated in Pvera

JAK2 mutation is found in Pvera and ET

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5389-5406). Kaplan Publishing. Kindle Edition.

Question 15

Rx of Pvera

Best initial therapy

Other Rx

Answer 15

Phlebotomy

Hydroxyurea is also used to lower the cell count

Daily aspirin should also be given

Anagrelide is used in the context of thrombocythemia.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5389-5406). Kaplan Publishing. Kindle Edition.

Question 16

Essential Thrombocythemia (ET)

Markedly elevated platelet count

CF

Most common causes of death

Rx

Answer 16

• Headache
• Visual disturbance
• Pain in the hands referred to as erythromelalgia

The most common causes of death are bleeding and thrombosis, with thrombosis being more common.

Therapy is with

• Hydroxyurea to lower the platelet count
• Anagrelide is an agent specific to the treatment of ET but it is not as strong as hydroxyurea
• Daily aspirin should also be given if patient is thrombosing.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5406-5416). Kaplan Publishing. Kindle Edition.

Question 17

Plasma Cell Disorders Multiple Myeloma (MM) The most frequent presentation of MM is with bone pain caused by a fracture occurring under normal use.

List the most common causes of death from MM

List the diagnostic tests to be done

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5406-5416). Kaplan Publishing. Kindle Edition.

Answer 17

Infection and and renal failure

Initial testing is as follows:

• Skeletal survey to detect punched out osteolytic lesions. (Osteoblastic lesions suggest metastatic prostate cancer.)
• Serum protein electrophoresis (SPEP): You are looking for elevated levels of monoclonal antibody (usually IgG).
• Urine protein electrophoresis (UPEP): Detects Bence-Jones protein.
• Peripheral smear: Shows “rouleaux” formation of blood cells.
• Elevated calcium level: Makes sense with the osteolytic lesions.
• Beta 2 microglobulin level: This is a prognostic indicator.
• BUN and creatinine: This is to detect the frequent occurrence of renal insufficiency.

The single most specific test is the bone marrow biopsy, which detects high numbers of plasma cells (10 percent).

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5416-5428). Kaplan Publishing. Kindle Edition.

Question 18

Rx of MM

Answer 18

Melphalan and steroids

Thalidomide, lenalidomide, or bortezomib may be added: Thalidomide is an inhibitor of tumor necrosis factor that has the same efficacy as chemotherapy.

The most effective therapy is an autologous stem cell bone marrow transplantation. This is reserved for patients who are relatively young (< 70) with advanced disease.

You should remember also to treat the hypercalcemia (hydration/ diuresis), bone fractures (bisphosphonates), renal failure (hydration), and anemia (erythropoietin) and to prophylax against infections with vaccinations (e.g., flu, pneumovax, tetanus, etc.).

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5430-5436). Kaplan Publishing. Kindle Edition.

Question 19

Waldenstrom’s Macroglobulinemia

This presents with hyperviscosity from IgM overproduction. The question will describe blurry vision, confusion, and headache. Enlarged nodes and spleen can be found.

Diagnostic Testing

Best initial Rx

Other Rx

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5442-5451). Kaplan Publishing. Kindle Edition.

Answer 19

There are no specific findings on CBC

The best initial test is a serum viscosity level, which will be markedly increased, and an SPEP, which will show an elevated IgM level

Best initial therapy: Plasmapheresis

Further treatment: Use the agents you would use for CLL, such as fludarabine or chlorambucil.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5442-5451). Kaplan Publishing. Kindle Edition.

Question 20

Rx of aplastic anemia

• <50years
• >50 years and/or no match

Answer 20

• Bone marrow transplant
• Antithymocyte globulin and cyclosporin

Question 21

Lymphoma presents with enlarged lymph nodes, most commonly in the cervical area. Hodgkin’s disease (HD) spreads centrifugally away from the center, starting at the neck. Non-Hodgkin’s lymphoma (NHL) more often presents as widespread disease

List the “B” symptoms of lymphoma

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5459-5471). Kaplan Publishing. Kindle Edition.

Answer 21

• Fever
• Weight loss
• Night sweats

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5459-5471). Kaplan Publishing. Kindle Edition.

Question 22

Best initial test for lymphoma

Answer 22

Best initial test for both HD and NHL: Excisional lymph node biopsy.

The major difference between HD and NHL is that HD has Reed-Sternberg cells.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5471-5490). Kaplan Publishing. Kindle Edition.

Question 23

Stages of Lymphoma

Answer 23

Stage I: Single lymph node group

Stage II: Two lymph node groups on one side of the diaphragm

Stage III: Lymph node involvement on both sides of the diaphragm

Stage IV: Widespread disease

HD and NHL present with stages as follows

• HD: 80– 90 percent present with Stages I and II
• NHL: 80– 90 percent present with Stages III and IV

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5471-5490). Kaplan Publishing. Kindle Edition.

Question 24

List the tests used in staging in lymphoma

Answer 24

• Chest x-ray
• CT scans (with contrast): Chest, abdomen, pelvis, and head
• Bone marrow biopsy

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5471-5490). Kaplan Publishing. Kindle Edition.

Question 25

True or False: Lymphoma evaluation does not need lymphangiogram or exploratory laparotomy of the abdomen Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5493-5502). Kaplan Publishing. Kindle Edition.

Answer 25

True. When these are in the choices, they are wrong Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5493-5502). Kaplan Publishing. Kindle Edition.

Question 26

Rx of lymphoma

Answer 26

Localized disease (Stages I and II) without “B” symptoms is treated predominantly with **radiation**. More advanced stage disease (Stages III and IV) is treated with chemotherapy: * HD: ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) * NHL: CHOP (cyclophosphamide, hydroxyadriamycin, Oncovin [vincristine], prednisone). Also, test for **anti-CD20 antigen**; if present, add **rituximab**, which adds efficacy to CHOP. Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5493-5502). Kaplan Publishing. Kindle Edition.

Question 27

Causes of aplastic anemia

Answer 27

* Cancers * **Radiation** and **toxins** such as toluene, insecticides (DDT), and benzene * **Drug effect**: sulfa, phenytoin, carbamazepine, chloramphenicol, alcohol * chemotherapy * SLE * PNH * Infection: HIV, hepatitis, CMV, EBV * B12 and folate deficiency * **Thyroid-inhibiting medications** such as propylthiouracil (PTU) and methimazole Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 219). Kaplan Medical Test Prep. Kindle Edition.

Question 28

A 54-year-old man comes to the emergency department for shortness of breath, blurry vision, confusion, and priapism. His WBC count is found to be 225,000/μL. The cells are predominantly neutrophils with about 4% blasts. What is the most appropriate next step in the management of this case? a. Leukapheresis b. BCR-ABL testing c. Bone marrow biopsy d. Bone marrow transplant e. Consult hematology/oncology f. Flow cytometry g. Hydroxyurea Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 224). Kaplan Medical Test Prep. Kindle Edition.

Answer 28

**A.** In acute leukostasis reaction, it is more important to remove the excessive white cells from the blood than to establish a specific diagnosis. Specific testing is not as important as treatment. No matter what the etiology, you still have to take the cells off. The symptoms are caused by blocking the delivery of oxygen to tissues because the red cells simply cannot get to the tissues. Afterward, you can establish a specific Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 224). Kaplan Medical Test Prep. Kindle Edition.

Question 29

Rx of CLL in the following scenarios: * Refractory cases * Mild cases * Severe infection * Autoimmune thrombocytopenia or hemolysis Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 226). Kaplan Medical Test Prep. Kindle Edition.

Answer 29

* Refractory cases: **cyclophosphamide** (more efficacy, but more toxic) * Mild cases: **chlorambucil** * Severe infection: **intravenous immunoglobulins** * Autoimmune thrombocytopenia or hemolysis: **prednisone** Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 226). Kaplan Medical Test Prep. Kindle Edition.

Question 30

List the differences between HD and NHL

Answer 30

HD typically present as local, stage I, and stage II in 80%–90%; NHL typically present as stage III and stage IV in 80%–90% HD centers around cervical area; NHL is often disseminated HD shows Reed-Sternberg cells on pathology; NHL does not show Reed-Sternberg cells HD pathologic classification: lymphocyte predominant has the best prognosis while lymphocyte depleted has the worst prognosis; in NHL, Burkitt and immunoblastic have the worst prognosis Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 228). Kaplan Medical Test Prep. Kindle Edition.

Question 31

Which of the following is the most useful to determine dosing of chemotherapy in HD? a. Echocardiogram b. Bone marrow biopsy c. Gender d. MUGA or nuclear ventriculogram e. Hematocrit f. Symptoms

Answer 31

**D**. Adriamycin (or doxorubicin) is cardiotoxic. The nuclear ventriculogram is the most accurate method of assessing left ventricular ejection fraction. **Use the MUGA scan to determine whether cardiac toxicity has occurred prior to the development of symptoms**. Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 229). Kaplan Medical Test Prep. Kindle Edition.

Question 32

List the adverse effects of the following chemotherapy agents: 1. Doxorubicin 2. Vincristine 3. Bleomycin 4. Cyclophosphamide 5. Cisplatin

Answer 32

1. Cardiomyopathy 2. Neuropathy 3. Lung fibrosis 4. Hemorrhagic cystitis 5. Renal and ototoxicity Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 229). Kaplan Medical Test Prep. Kindle Edition.

Question 33

A 69-year-old woman is admitted with severe back pain that has suddenly worsened. She also feels a “pop” when she coughs followed by tenderness over the ribs. X-ray shows lytic lesions. Her calcium level is 2 points above normal, the hematocrit is 27%, and her creatinine is elevated. Urinalysis shows trace protein, but the 24-hour urine show 5 grams of protein. What do you expect to find on technetium bone scan? a. Normal b. Lytic lesions at the site of the fractures c. Increased uptake diffusely d. Decreased uptake

Answer 33

**A**. The radionuclide bone scan will be normal because lytic lesions do not pick up the nuclear isotope. Nuclear bone scan shows increased uptake with osteoblastic activity, which is absent in myeloma. Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 230). Kaplan Medical Test Prep. Kindle Edition.

Question 34

What is the explanation for the difference between the urinary level of protein on urinalysis and the 24-hour urine? a. False positive 24-hour urine is common in myeloma. b. Calcium in urine creates a false negative urinalysis. c. Uric acid creates a false positive 24-hour urine. d. Bence-Jones protein is not detected by dipstick. e. IgG in urine inactivates the urine dipstick.

Answer 34

**D**. **Bence-Jones protein is detected by urine immunoelectrophoresis**. The urine dipstick will detect only albumin. Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 230). Kaplan Medical Test Prep. Kindle Edition.

Question 35

What is the single most accurate test for myeloma? a. Skull x-rays b. Bone marrow biopsy c. 24-hour urine d. SPEP e. Urine immunoelectrophoresis (Bence-Jones protein) Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 230). Kaplan Medical Test Prep. Kindle Edition.

Answer 35

**B**. **Nothing besides myeloma is associated with greater than 10% plasma cells on bone marrow biopsy**. The most common wrong answer is SPEP. Of those with an “M-spike” of immunoglobulins, 99% do not have myeloma. Most IgG spikes are from monoclonal gammopathy of unknown significance that does not progress or need treatment. Skull x-rays show lytic lesions, but this is not as specific as massive plasma cell levels in the marrow. Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 231). Kaplan Medical Test Prep. Kindle Edition.

Question 36

**Multiple myeloma** * Best initial Rx * Rx for candidates not for BIRx * Most effective Rx

Answer 36

* Combination of dexamethasone with either lenalidomide or bortezomib; OR dexamethasone and lenalidomide and bortezomib * Melphalan is useful in older, fragile patients who cannot tolerate adverseeffects. **MPT** = Melphalan + Prednisone + Thalidomide; **MPV** = Melphalan + Prednisone + Bortezomib (Velcade) * The most effective therapy in those under age 70 is an autologous bone marrow transplant with stem cell support. **This is used after induction chemotherapy with lenalidomide and steroids.** Fischer, Conrad (2012-11-01). Master the Boards USMLE Step 2 CK (Page 231). Kaplan Medical Test Prep. Kindle Edition.

Question 37

Rx of ALL

Answer 37

* Vincristine * Predinisone * Daunorubicine * +- Asparaginase

Question 38

List the causes of JAK2 mutation

Answer 38

* Polycythemia rubra vera * Essential thrombocytopenia

Question 39

Diagnosis: * Elevated neutrophil count * Low Leukocyte alkaline phosphatase

Answer 39

CML