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 in management because the patient's negative peripheral blood test for Fanconi anemia does not rule out the possibility of having this condition. Skin fibroblast culture testing is more sensitive for detecting Fanconi anemia compared to peripheral blood testing. Given the family history of aplastic anemia and leukemia, along with the sister's poor response to treatment, it is crucial to definitively confirm or rule out Fanconi anemia as the underlying cause. Administering ATG and cyclosporine (choice A) without confirming the diagnosis may not be effective. Searching for a donor for matched unrelated transplant (choice B) is premature without confirming the diagnosis. Sending a bone marrow aspirate for Fanconi anemia testing (choice C) may not be as sensitive as skin fibroblast culture testing.

Correct Answer: C

Rationale: The correct answer is C: Stage III. Rationale: 1. In the St. Jude (Murphy) staging system for non-Hodgkin lymphoma, Stage III is defined as the presence of a mediastinal mass that is greater than 33% of the thoracic diameter. 2. The patient in the scenario has a large mediastinal mass that meets this criteria, placing her in Stage III. 3. The absence of disease in other sites, as confirmed by the metastatic work-up, indicates that the disease is localized to the mediastinum. 4. Therefore, based on the specific criteria of the St. Jude (Murphy) staging system, the correct stage for this patient's non-Hodgkin lymphoma is Stage III. Summary of other choices: - Choice A: Stage I would not be appropriate as the mass is not localized to a single lymph node region. - Choice B: Stage II would not be correct as the mass extends beyond a

Correct Answer: C

Rationale: The correct answer is C: Granisetron, dexamethasone at 50% dosing, and арrepitant. This regimen is recommended by guidelines for moderate emetogenic chemotherapy in children. Granisetron is a first-line antiemetic for children, and combining it with dexamethasone and арrepitant provides a synergistic effect in preventing CINV. Dexamethasone at 50% dosing is preferred in children to reduce the risk of side effects. Palonosetron and olanzapine (choice A) are not typically recommended as first-line agents in pediatric patients. Dexamethasone and арrepitant (choice B) do not cover the full spectrum of CINV prevention compared to the correct regimen. Using dexamethasone at 100% dosing (choice D) may increase the risk of side effects in children without additional benefit in preventing CINV

Correct Answer: C

Rationale: Rationale: The correct answer is C: MYH9, as mutations in the MYH9 gene are associated with May-Hegglin anomaly, which presents with thrombocytopenia and hearing loss. NBEAL2 (choice A) is linked to gray platelet syndrome, not hearing loss. GP-1Ba (choice B) is a platelet glycoprotein, not associated with hearing loss. Deletions of the long arm of chromosome 11 (choice D) are related to Jacobsen syndrome, which presents with thrombocytopenia but not hearing loss. Thus, based on the presented clinical findings, MYH9 is the most likely gene responsible.

Correct Answer: D

Rationale: The correct answer is D because platinum-associated hearing loss is primarily due to the destruction of the cochlear hair cells, leading to sensorineural hearing loss. This type of hearing loss affects the inner ear's ability to transmit sound signals to the brain. Platinum chemotherapy drugs are ototoxic and can damage the hair cells in the cochlea, resulting in permanent hearing loss. Choices A and B are incorrect because platinum chemotherapy typically causes sensorineural, not conductive, hearing loss, and high-frequency volumes are usually affected first. Choice C is incorrect because younger age at exposure is actually a risk factor for platinum-associated hearing loss due to the vulnerability of developing auditory structures.