You examine a 10-year-old boy with severe aplastic anemia. He has no dysmorphic features and is at the 50th percentile for height and weight. Family history includes a sister with aplastic anemia unresponsive to anti-human thymocyte globulin (ATG) and cyclosporine who died early in the course of an unrelated donor hematopoietic stem cell transplant complicated by severe mucositis and transplant-related organ toxicities. There are no other siblings. A cousin died of acute myeloid leukemia at age 5 years. A peripheral blood sample test for Fanconi anemia is negative with no increased chromosomal breaks in response to diepoxybutane or mitomycin C. Which of the following is the most important next step in management?

Correct Answer: D

Rationale: The correct answer is D: Send a skin fibroblast culture for Fanconi anemia testing. This is the most important next step because the patient has a family history suggestive of Fanconi anemia, which is an inherited bone marrow failure syndrome. Aplastic anemia in a child with a family history of bone marrow failure syndromes raises suspicion for inherited causes like Fanconi anemia. Testing for Fanconi anemia involves assessing chromosomal breakage in response to DNA cross-linking agents like diepoxybutane or mitomycin C, which is best done using skin fibroblast culture. This specific test can confirm or rule out Fanconi anemia as the underlying cause of aplastic anemia in this patient. The other choices are incorrect because administering ATG and cyclosporine (Choice A) may not be effective if the underlying cause is Fanconi anemia. Searching for a donor for matched unrelated transplant (Choice B) is premature without confirming the diagnosis.

Correct Answer: C

Rationale: The correct answer is C: Stage III. According to the St. Jude (Murphy) staging system for non-Hodgkin lymphoma, Stage III is defined as disease that extends beyond a single region (e.g., thorax) on one side of the diaphragm. In this case, the large mediastinal mass greater than 33% of thoracic diameter indicates involvement beyond a single region. The absence of disease in other sites based on the metastatic work-up rules out Stages IV. Since there is no information provided to suggest involvement on both sides of the diaphragm, Stage III is the most appropriate stage for this patient. Choice A (Stage I) is incorrect as the disease extends beyond a single region. Choice B (Stage II) is incorrect as it implies involvement on both sides of the diaphragm, which is not indicated. Choice D (Stage IV) is incorrect as there is no evidence of distant metastasis in the given scenario.

Correct Answer: C

Rationale: The correct answer is C: Granisetron, dexamethasone at 50% dosing, and aprepitant. Granisetron is a first-line antiemetic for CINV in chemotherapy. Dexamethasone at 50% dosing is effective in reducing nausea and vomiting. Aprepitant, a neurokinin-1 receptor antagonist, is recommended for moderate to high emetogenic chemotherapy regimens like cisplatin. This combination provides a comprehensive approach targeting different pathways involved in CINV. Choice A is incorrect because olanzapine is not typically used in pediatric patients for CINV prevention. Choice B is incorrect as aprepitant is preferred over olanzapine. Choice D is incorrect because excessive dexamethasone dosing can increase the risk of side effects without additional benefit.

Correct Answer: C

Rationale: Rationale for correct answer (C - MYH9): 1. MYH9 gene encodes for non-muscle myosin heavy chain IIA. 2. Mutations in MYH9 gene are associated with May-Hegglin anomaly, characterized by thrombocytopenia without bleeding tendency. 3. Additionally, MYH9-related disorders can present with sensorineural hearing loss. 4. Given the patient's thrombocytopenia and hearing loss, MYH9 gene is the most likely culprit. Summary of incorrect choices: A: NBEAL2 - Associated with gray platelet syndrome, not consistent with patient's presentation. B: GP-1Ba - Glycoprotein Ib-IX-V complex gene, not linked to the symptoms described. D: Deletions of long arm of chromosome 11 - Not specific to thrombocytopenia and hearing loss in this context.

Correct Answer: D

Rationale: The correct answer is D. Platinum-associated hearing loss is due to the destruction of the cochlear hair cells. Platinum-based chemotherapy agents can cause ototoxicity, leading to sensorineural hearing loss by damaging the hair cells in the cochlea. This type of hearing loss affects the ability to hear high-frequency sounds first. Low-frequency volumes are typically preserved. Older age at exposure does not increase the risk of platinum-associated hearing loss. Conductive hearing loss is not typically associated with platinum chemotherapy. In summary, the correct answer is D because platinum-associated hearing loss affects the cochlear hair cells, leading to sensorineural hearing loss predominantly in high-frequency sounds.