Question:
A patient with acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation shows no clinical improvement despite treatment with high-dose corticosteroids. Which of the following is the next best drug to use?
A patient with acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation shows no clinical improvement despite treatment with high-dose corticosteroids. Which of the following is the next best drug to use?
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Ruxolitinib is also approved for the treatment of steroid-refractory *chronic* GVHD.
Its primary adverse effects include dose-dependent cytopenias (thrombocytopenia and anemia) and an increased risk of severe infections due to immunosuppression, necessitating careful monitoring.
Its primary adverse effects include dose-dependent cytopenias (thrombocytopenia and anemia) and an increased risk of severe infections due to immunosuppression, necessitating careful monitoring.
Updated On: Sep 3, 2026
- Ruxolitinib
- Tacrolimus
- Mycophenolate mofetil
- Etanercept
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The Correct Option is A
Solution and Explanation
Concept:
The patient has developed acute Graft-Versus-Host Disease (aGVHD) following an allogeneic hematopoietic stem cell transplant.
The standard first-line therapy for severe aGVHD is high-dose systemic corticosteroids (usually methylprednisolone).
However, the patient is refractory to steroids, and we must select the most appropriate second-line agent.
Explanation:
• Acute GVHD occurs when donor immune cells (primarily mature T cells) recognize the recipient's tissues as foreign and mount an aggressive immune attack, typically targeting the skin, liver, and gastrointestinal tract.
• When aGVHD does not respond to initial high-dose corticosteroids (steroid-refractory aGVHD), the prognosis is historically very poor, and second-line therapy is urgently required.
• The pathophysiology of GVHD relies heavily on pro-inflammatory cytokines whose signaling is mediated intracellularly via the Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway.
• Ruxolitinib is an oral, selective inhibitor of JAK1 and JAK2.
• By inhibiting the JAK-STAT signaling pathway, Ruxolitinib effectively dampens the activation and proliferation of alloreactive T cells and reduces the production of inflammatory cytokines.
• Based on highly successful clinical trials (such as the REACH2 trial), Ruxolitinib is now the only drug specifically FDA-approved for the treatment of steroid-refractory acute GVHD in patients 12 years and older.
• It has demonstrated superior overall response rates and increased survival compared to other conventional salvage therapies.
• Tacrolimus and Mycophenolate mofetil are heavily used for GVHD prophylaxis and sometimes as part of initial therapy, but they are less effective as single salvage agents once the disease is established and steroid-refractory.
• Etanercept (a TNF inhibitor) has been used off-label in the past with limited and inconsistent success.
• Therefore, Ruxolitinib is definitively the next best drug.
Final answer:
Ruxolitinib is the drug of choice for steroid-refractory acute GVHD.
The patient has developed acute Graft-Versus-Host Disease (aGVHD) following an allogeneic hematopoietic stem cell transplant.
The standard first-line therapy for severe aGVHD is high-dose systemic corticosteroids (usually methylprednisolone).
However, the patient is refractory to steroids, and we must select the most appropriate second-line agent.
Explanation:
• Acute GVHD occurs when donor immune cells (primarily mature T cells) recognize the recipient's tissues as foreign and mount an aggressive immune attack, typically targeting the skin, liver, and gastrointestinal tract.
• When aGVHD does not respond to initial high-dose corticosteroids (steroid-refractory aGVHD), the prognosis is historically very poor, and second-line therapy is urgently required.
• The pathophysiology of GVHD relies heavily on pro-inflammatory cytokines whose signaling is mediated intracellularly via the Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway.
• Ruxolitinib is an oral, selective inhibitor of JAK1 and JAK2.
• By inhibiting the JAK-STAT signaling pathway, Ruxolitinib effectively dampens the activation and proliferation of alloreactive T cells and reduces the production of inflammatory cytokines.
• Based on highly successful clinical trials (such as the REACH2 trial), Ruxolitinib is now the only drug specifically FDA-approved for the treatment of steroid-refractory acute GVHD in patients 12 years and older.
• It has demonstrated superior overall response rates and increased survival compared to other conventional salvage therapies.
• Tacrolimus and Mycophenolate mofetil are heavily used for GVHD prophylaxis and sometimes as part of initial therapy, but they are less effective as single salvage agents once the disease is established and steroid-refractory.
• Etanercept (a TNF inhibitor) has been used off-label in the past with limited and inconsistent success.
• Therefore, Ruxolitinib is definitively the next best drug.
Final answer:
Ruxolitinib is the drug of choice for steroid-refractory acute GVHD.
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