A 4-year-old child with acute lymphoblastic leukemia is receiving high-dose methotrexate during interim maintenance. He receives ondansetron and арrepitant during his stay, which control his nausea and vomiting well. These medications work by inhibiting signaling in which part of the brain?

Correct Answer: E

Rationale: The correct answer is D: Vomiting center. Ondansetron and aprepitant are antiemetic medications that work by inhibiting signaling in the vomiting center of the brain. The vomiting center is located in the medulla oblongata in the brainstem, which plays a crucial role in triggering the reflexes that lead to nausea and vomiting. By blocking signals in the vomiting center, these medications effectively prevent and control nausea and vomiting. Incorrect choices: A: The vestibular system is responsible for balance and spatial orientation, not for controlling nausea and vomiting. B: The cerebral cortex is involved in higher brain functions such as thinking and decision-making, not in regulating nausea and vomiting. C: The hypothalamus regulates various physiological processes like temperature regulation and hormone release, but it is not directly involved in controlling nausea and vomiting.

Correct Answer: D

Rationale: The correct answer is D: Dexamethasone exposure. Dexamethasone is a corticosteroid commonly used in the treatment of acute lymphoblastic leukemia. It can cause avascular necrosis of the hip due to its effect on bone metabolism, leading to increased hip pain during weight-bearing activities. This is a known side effect seen more commonly in patients exposed to dexamethasone. Incorrect Choices: A: Younger age at diagnosis - Age is not a known risk factor for avascular necrosis in this context. B: Non-White race - Race is not a known risk factor for avascular necrosis in this context. C: Low body-mass index - Body mass index is not a known risk factor for avascular necrosis in this context.

Correct Answer: B

Rationale: The correct answer is B: Hyperleukocytosis; leukapheresis or manual exchange transfusion and initiation of induction chemotherapy. In this scenario, the patient's symptoms and lab findings are consistent with acute myeloid leukemia (AML) with leukostasis, causing hypoxia and interstitial infiltrates. Leukapheresis or manual exchange transfusion is crucial to rapidly reduce the high white blood cell count, which can help alleviate symptoms and prevent complications like tissue hypoxia. Initiation of induction chemotherapy is also essential for long-term management of AML. Rationale for why other choices are incorrect: A: Hyperleukocytosis alone without leukostasis does not typically require immediate leukoreduction, as in this case. Induction chemotherapy should be initiated promptly to address the underlying AML. C: COVID-19 infection would not typically present with such profound leukocytosis and monocytic morphology. Convalescent plasma and prednisone are not

Correct Answer: A

Rationale: The correct answer is A: CXCR4. In this case, the patient presents with severe neutropenia, recurrent infections, and warts, suggestive of WHIM syndrome, where CXCR4 mutations are often involved. CXCR4 plays a crucial role in immune cell trafficking and retention in the bone marrow. The hypercellular marrow and vacuolated myeloid cells are consistent with WHIM syndrome. The absence of abnormalities in red cells or platelet precursors rules out other syndromes. Mutations in ELANE are commonly associated with congenital neutropenia, not familial inherited bone marrow failure syndromes. GATA2 mutations are linked to familial myelodysplastic syndromes, not typically presenting with neutropenia and warts. Mitochondrial DNA mutations are more related to mitochondrial disorders, which usually manifest with multi-system involvement, not specific to bone marrow failure syndromes.

Correct Answer: B

Rationale: The correct answer is B: Acute myeloid leukemia-like. In JMML, a disease signature resembling acute myeloid leukemia (AML) has been associated with a poor outcome. This signature includes features such as increased blasts, abnormal karyotypes, and mutations in genes like NRAS and KRAS. AML-like JMML cases often have aggressive disease progression and poorer response to treatment. Tyrosine kinase inhibitors (choice A) are not typically used in JMML treatment. Chronic myeloid leukemia-like (choice C) is not associated with a poor outcome in JMML. BRAF pathway abnormalities (choice D) may be present in some cases of JMML but are not the primary disease signature predicting poor outcomes.