A 48-year-old man, 3 months after heart transplantation, presents with worsening fatigue and new bruising. He denies fevers, chills, or bleeding from other sites. Vital signs are: T 36.8°C, BP 104/68 mm Hg, HR 88/min, RR 16/min, SpO₂ 98% on room air. His maintenance immunosuppression includes tacrolimus, mycophenolate mofetil, and valganciclovir for CMV prophylaxis. Laboratory results show: WBC 4.2 × 10³/µL, hemoglobin 9.8 g/dL, platelets 45 × 10³/µL, and a tacrolimus trough level of 8.2 ng/mL (target 5–10 ng/mL). Which of the following is the most likely etiology of his cytopenias?

A 45-year-old man is on the bone marrow transplant unit on day +40 following an allogeneic hematopoietic stem cell transplant for acute myeloid leukemia. Over the past 24 hours, he has developed a maculopapular rash covering approximately 30% of his body surface area and has had three episodes of watery, non-bloody diarrhea. His total bilirubin is 1.5 mg/dL (baseline 0.8 mg/dL), he is afebrile, and his white blood cell count is stable. Stool studies for infectious pathogens are pending. Which of the following is the most appropriate next step to confirm the diagnosis and guide management?

A 34-year-old woman is evaluated on day +45 after an allogeneic stem-cell transplant for acute myeloid leukemia. She has developed a diffuse maculopapular rash covering about 60% of her body surface area, and nursing records show watery diarrhea totaling 1600 mL over the past 24 hours. Her most recent total bilirubin is 1.5 mg/dL (normal 0.1–1.2 mg/dL). Based on these findings, what is the overall stage of her acute graft-versus-host disease (GVHD)?

A 48-year-old man, 3 weeks after allogeneic hematopoietic stem cell transplant for acute leukemia, is admitted to the ICU with new-onset fever and hypotension. He is on assist-control mechanical ventilation (FiO₂ 0.5, PEEP 8 cm H₂O) for respiratory distress and receiving norepinephrine at 0.1 mcg/kg/min via a central venous catheter to maintain MAP ≥65 mmHg. His immunosuppressive regimen includes tacrolimus and mycophenolate. Vital signs are: T 38.5°C, HR 110 bpm, BP 90/55 mmHg (on norepinephrine), RR 16 (ventilator), SpO₂ 92%. Laboratory results: WBC 1.8×10³/mm³, ANC 350/mm³, platelets 80×10³/mm³, hemoglobin 8.5 g/dL. He reports generalized malaise and has white, scraping plaques on his tongue. Given this presentation, which of the following immediate complications is most concerning and requires prompt intervention?

A 62-year-old male, 3 months after kidney transplantation, is admitted to the ICU with increasing fatigue and a low-grade fever. He is on assist-control ventilation for suspected pneumonia and receiving a continuous tacrolimus infusion via a central line. His laboratory results are: WBC 2.2 × 10^3/mm^3, ANC 350/mm^3, Hemoglobin 10.5 g/dL, and Platelets 180 × 10^3/mm^3. Which hematologic abnormality poses the greatest immediate risk for infection in this patient?

A 48-year-old man, 6 weeks after kidney transplantation, is in the intensive care unit with worsening fatigue and malaise. His immunosuppression regimen includes tacrolimus and mycophenolate mofetil, and he receives valganciclovir and trimethoprim–sulfamethoxazole prophylaxis. Vital signs are: blood pressure 118/72 mm Hg, heart rate 96 bpm, and temperature 37.8 °C. Morning laboratory results show: WBC 2.1 × 10^3/µL (ANC 400/µL), hemoglobin 7.8 g/dL, and platelets 8,000/µL. Physical examination reveals scattered petechiae on his extremities without active bleeding. Which of the following hematological complications requires the MOST immediate prioritization for intervention?

A 52-year-old man is evaluated on day +45 following an allogeneic stem cell transplant for acute myeloid leukemia. He is on a dedicated transplant unit with continuous cardiac monitoring. Nursing rounds note a new, diffuse maculopapular rash covering approximately 60% of his body surface area. The patient reports multiple episodes of watery diarrhea, with a 24-hour stool volume of 1,200 mL. Laboratory results show a total bilirubin of 3.5 mg/dL (normal 0.1–1.2 mg/dL). His immunosuppressive regimen consists of tacrolimus and mycophenolate mofetil. Using the modified Glucksberg criteria for acute graft-versus-host disease (GVHD), what is the patient’s overall aGVHD grade?

A 48-year-old man, 3 months after kidney transplantation, is in the ICU for septic shock secondary to pneumonia. He is intubated, receiving vasopressor support via a central venous catheter, and under continuous cardiac monitoring. His maintenance immunosuppression includes mycophenolate mofetil and tacrolimus. Over the past week, his absolute neutrophil count (ANC) has fallen from 1,200/mm³ to 350/mm³. Three days ago, mycophenolate mofetil was reduced to 500 mg twice daily, and valganciclovir prophylaxis was stopped yesterday. Despite administration of standard-dose granulocyte colony-stimulating factor (G-CSF), his ANC remains 350/mm³. His latest tacrolimus trough is within the target range. Which of the following is the most appropriate next adjustment to his regimen to manage persistent neutropenia?

A 48-year-old man, 3 months post–kidney transplant, is admitted to the ICU for septic shock. Initial vital signs are blood pressure 85/50 mm Hg on norepinephrine 0.2 mcg/kg/min, heart rate 110 beats/min, temperature 38.5 °C, and respiratory rate 24 breaths/min. He is on assist-control ventilation and a central norepinephrine infusion. His immunosuppression consists of tacrolimus (trough 8 ng/mL) and mycophenolate mofetil 1000 mg twice daily. Labs show WBC 1.8 × 10³/µL (ANC 450/µL), platelets 45 × 10³/µL, and hemoglobin 9.2 g/dL; there is no active bleeding. Which of the following is the MOST appropriate initial adjustment to his immunosuppressive regimen?

A 48-year-old man, 3 months post–kidney transplant, is in the ICU for acute respiratory distress and is intubated on assist-control ventilation. He requires vasopressors via a central line. His immunosuppression includes tacrolimus and mycophenolate mofetil (MMF). He also receives trimethoprim-sulfamethoxazole for Pneumocystis jirovecii prophylaxis and valganciclovir for CMV prophylaxis. Recent labs show WBC 1.8 × 10³/mm³ with an ANC of 350/mm³ (neutropenia) and platelets 180 × 10³/mm³. Tacrolimus trough is therapeutic. Blood and respiratory cultures are pending. Considering his severe neutropenia, which of the following is the MOST appropriate initial pharmacotherapy adjustment?