Free USMLE Step 2 CK Hematology and Oncology practice questions

Cisplatin is the prototype of highly emetogenic chemotherapy, causing emesis in more than 90% of patients without prophylaxis, with both an acute phase (first 24 hours, driven by serotonin) and a delayed phase (peaking at 48 to 72 hours, driven by substance P). ASCO and NCCN recommend a 4-drug regimen for adults receiving cisplatin or an anthracycline plus cyclophosphamide: an NK1 receptor antagonist (aprepitant or fosaprepitant), a 5-HT3 receptor antagonist (ondansetron, granisetron, or palonosetron), dexamethasone, and olanzapine, given on day 1, with dexamethasone and olanzapine continued on days 2 to 4 to cover the delayed phase. Aprepitant inhibits CYP3A4 and raises dexamethasone levels, so the steroid dose is reduced when they are combined. Olanzapine causes sedation, so a 5-mg dose at bedtime is an option. Preventing emesis completely from the first cycle is important because poorly controlled vomiting conditions anticipatory nausea in later cycles.

A. A 5-HT3 antagonist with dexamethasone is the standard 2-drug regimen for moderately emetogenic chemotherapy and leaves the delayed, substance P-mediated phase of cisplatin emesis undertreated. B. Ondansetron alone is suitable only for low-risk regimens. D. Lorazepam is used for anticipatory nausea and as an adjunct, not as core prophylaxis. E. Metoclopramide is a breakthrough agent; it is less effective than the recommended classes and causes extrapyramidal reactions.

Hypotension, hypoxia, wheezing and angioedema within minutes of starting a transfusion define an anaphylactic transfusion reaction. That it occurs with her first-ever transfusion, in a woman with recurrent sinopulmonary infections and celiac disease (both associated with selective IgA deficiency), points to anti-IgA antibodies in an IgA-deficient recipient reacting to IgA in donor plasma. No prior transfusion is needed because these antibodies can form without known exposure.

The life-saving drug is epinephrine, given intramuscularly in the anterolateral thigh (0.3 to 0.5 mg of 1 mg/mL, repeated every 5 to 15 minutes as needed), which reverses vasodilation, bronchospasm and airway edema. The transfusion has correctly been stopped and saline started; supportive care includes oxygen, airway monitoring, fluid boluses and an inhaled bronchodilator, and the reaction is reported to the blood bank. Afterward, measure IgA and anti-IgA levels and give future transfusions as washed red cells or IgA-deficient products (plasma and platelets from IgA-deficient donors).

A. Diphenhydramine treats urticaria and pruritus in a mild allergic reaction and is only an adjunct in anaphylaxis; it does not treat hypotension or airway edema. C. Methylprednisolone has an onset of hours and does not reverse acute anaphylaxis. D. Furosemide treats transfusion-associated circulatory overload, which presents with hypertension, elevated JVP and crackles, not hypotension with angioedema. E. Acetaminophen is used for febrile nonhemolytic reactions; she is afebrile and in shock.

This man has a very low MCV with only mild anemia, a high RBC count, a normal RDW, target cells, and normal iron studies. The Mentzer index (MCV divided by RBC count in millions) is 64 / 6.2, about 10, which is below 13 and favors thalassemia trait over iron deficiency. His Mediterranean ancestry and a mother whose "low iron" never responded to iron add to the picture. In thalassemia trait the marrow makes increased numbers of small cells, so the RBC count is preserved or high, unlike iron deficiency, in which production falls along with cell size.

The next step is hemoglobin electrophoresis (or high-performance liquid chromatography). An elevated HbA2 (above about 3.5%), sometimes with a modestly raised HbF, confirms beta-thalassemia trait. If electrophoresis is normal in this setting, alpha-thalassemia trait is likely; it is a diagnosis of exclusion or of DNA testing, because adult electrophoresis is normal. Confirming the diagnosis matters because it avoids repeated futile iron therapy (and iron overload) and allows reproductive counseling and partner testing.

A. A bone marrow iron stain looks for ringed sideroblasts, but sideroblastic anemia typically shows a high ferritin and saturation and is not suggested by a high RBC count with target cells; marrow examination is invasive and unnecessary here. B. Lead poisoning causes basophilic stippling and an exposure history, neither present. D. Colonoscopy evaluates iron deficiency in men and postmenopausal women, but his iron studies are normal. E. Erythropoietin levels help in suspected chronic kidney disease or polycythemia, not in isolated microcytosis.

This patient has a supratherapeutic INR without bleeding, explained by a classic drug interaction: trimethoprim-sulfamethoxazole inhibits CYP2C9 metabolism of S-warfarin and displaces it from albumin. For an INR between 4.5 and 10 with no bleeding, the American College of Chest Physicians guideline and the 2020 ACC expert consensus pathway recommend holding one or two doses of warfarin, rechecking the INR soon, and resuming at the same or a slightly reduced dose once the INR returns to range, without routine vitamin K. Randomized trials showed that low-dose oral vitamin K in this range lowers the INR faster but does not reduce bleeding or thromboembolism. The precipitating antibiotic has already been stopped, so the INR should drift down over a few days. Oral vitamin K (2.5 to 5 mg) is reserved for an INR above 10 without bleeding.

A. Oral vitamin K 5 mg is appropriate for an INR above 10, but at 7.2 it adds no clinical benefit and, in a patient with prior stroke, can cause warfarin resistance and a period of subtherapeutic anticoagulation. B. Intravenous vitamin K with 4-factor prothrombin complex concentrate is for major or life-threatening bleeding, such as intracranial or gastrointestinal hemorrhage with instability; using it here exposes a high-risk patient to rebound thrombosis. D. Fresh frozen plasma is a slower, volume-heavy reversal agent inferior to prothrombin complex concentrate and has no role without bleeding. E. Switching to a DOAC may be reasonable later for a patient with labile INRs, but this patient has been stable for a year and the elevation has a transient, identified cause; starting apixaban while the INR is 7.2 would also stack anticoagulants.

Patients with aplastic anemia, especially while receiving antithymocyte globulin and when they are potential transplant candidates, should receive irradiated, leukoreduced blood products from unrelated donors. He clearly needs transfusion now: platelets for bleeding and a count below 10,000/uL, and red cells for a hemoglobin below 7 g/dL.

Each feature has a reason. Irradiation inactivates donor T lymphocytes, preventing transfusion-associated graft-versus-host disease, which is nearly always fatal in a patient whose T cells are being depleted by ATG. Leukoreduction lowers the rate of HLA alloimmunization (which causes platelet refractoriness and graft rejection), CMV transmission, and febrile nonhemolytic reactions. Products from family members are avoided because they sensitize the recipient to minor histocompatibility antigens that a related or haploidentical donor might share, raising the risk of graft rejection; directed donation from a first-degree relative also carries a higher risk of transfusion-associated GVHD because of shared HLA haplotypes. Transfusions should still be kept to the minimum needed.

A. Directed donation from his son is wrong on two counts: it risks sensitization against a potential donor and, if unirradiated, transfusion-associated GVHD from partially HLA-matched lymphocytes. B. Leukoreduction alone does not reliably remove enough viable T cells to prevent transfusion-associated GVHD; irradiation is required during ATG therapy. D. Washing removes plasma proteins and helps prevent allergic reactions or reactions in IgA-deficient patients, but it does not inactivate lymphocytes. E. Fresh whole blood from a relative combines every risk: unirradiated lymphocytes, HLA sensitization against a family donor, and no component targeting.

Headache, fatigue and an enlarged pituitary gland in a patient receiving ipilimumab (anti-CTLA-4), especially combined with nivolumab, indicate immune checkpoint inhibitor hypophysitis. The labs show central (secondary) adrenal insufficiency, with a low cortisol and an inappropriately low ACTH, plus central hypothyroidism, with a low free T4 and a low or inappropriately normal TSH. Potassium is normal because the renin-angiotensin-aldosterone axis is intact in pituitary disease. Her orthostatic hypotension, hyponatremia and low-normal glucose show that cortisol deficiency is clinically significant.

The first drug is a glucocorticoid: hydrocortisone at physiologic replacement doses (higher stress doses if she were in crisis). Levothyroxine is added only after glucocorticoid replacement has begun, usually several days later, because thyroid hormone increases cortisol metabolism and can precipitate adrenal crisis. Endocrine irAEs are treated with hormone replacement, and high-dose immunosuppressive steroids are reserved for severe mass effect such as visual compromise or intractable headache. Replacement is usually lifelong, and the checkpoint inhibitor can often be resumed once she is stable.

A. Levothyroxine first is the classic error; it accelerates cortisol clearance in a patient with untreated adrenal insufficiency. C. Fludrocortisone is needed for primary adrenalitis, where aldosterone is lost (hyperkalemia, high ACTH), not for central adrenal insufficiency. D. Infliximab is the second-line agent for steroid-refractory immune colitis and plays no role in hypophysitis. E. Cabergoline treats prolactinomas and hyperprolactinemia, not inflammatory pituitary failure.

Thrombophilia testing is reasonable here because the result could change management: she is young, the clot was unprovoked, she has a strong family history, and pregnancy planning (and counseling of relatives) may depend on the answer. The question is which tests are valid now, 10 days after an acute clot and while she takes a DOAC.

Genetic tests for factor V Leiden and the prothrombin G20210A mutation detect a DNA sequence and are unaffected by acute thrombosis, heparin, warfarin or direct oral anticoagulants, so they can be sent at any time. Factor V Leiden is the most common inherited thrombophilia, especially in people of European ancestry, and its interaction with estrogen and pregnancy makes it particularly relevant to her plans.

Functional assays are distorted in this setting. An acute clot consumes natural anticoagulants, heparin lowers antithrombin, warfarin lowers proteins C and S, and DOACs interfere with clot-based assays. Guidance (ASH and the British Society for Haematology) is to defer these assays until at least 3 months after the event and, when possible, off anticoagulation, without ever stopping treatment of an acute clot simply to test.

A. Antithrombin activity falls with acute thrombosis and can be falsely low, and anti-Xa based assays are affected by apixaban. B. Free protein S falls with acute thrombosis, inflammation, pregnancy and estrogen, so a low value now proves nothing. C. Lupus anticoagulant clotting assays, including the dRVVT, give false positives on DOACs and heparin. D. Protein C activity is consumed by the acute clot and is unreliable until months later.

This asymptomatic man has no CRAB features: hemoglobin is above 10 g/dL, calcium and creatinine are normal, and CT shows no lytic lesions. On marrow burden alone (10% to 60% clonal plasma cells) he would be classified as smoldering myeloma and observed. However, the 2014 International Myeloma Working Group criteria added three SLiM biomarkers that predict about an 80% risk of progression to end-organ damage within 2 years and therefore define active myeloma even without CRAB: Sixty percent or more clonal marrow plasma cells, an involved to uninvolved serum free Light chain ratio of 100 or more (with the involved light chain at least 100 mg/L), and more than one focal lesion 5 mm or larger on MRI. Here the lambda to kappa ratio is 1,480 / 11.2, about 132, and the involved lambda level is far above 100 mg/L. This single biomarker converts the diagnosis from smoldering to active multiple myeloma, and treatment is indicated.

A. Bone marrow clonal plasma cells of 34% meet the 10% threshold for myeloma but fall in the smoldering range; only 60% or more is a myeloma-defining event. C. Serum beta-2 microglobulin of 3.9 mg/L is used with albumin (and LDH and cytogenetics in the revised system) to stage established myeloma; it is prognostic, not diagnostic. D. IgA isotype of the monoclonal protein is a modest risk factor for progression of MGUS and smoldering disease but is not a myeloma-defining event. E. Serum M-protein of 2.6 g/dL is below even the 3 g/dL smoldering threshold, and the size of the spike alone never mandates treatment.