›Antihistamines for pruritus
›Cetirizine 10 mg PO daily or hydroxyzine 25 mg PO as needed
›Sedating antihistamines with caution in frail or elderly
Grade II to IV GVHD systemic treatment
›First-line systemic corticosteroids
›Skin or lower GI or liver GVHD (Grade II to IV)
›Methylprednisolone 1 to 2 mg/kg/day IV or PO
›Grade II: 1 mg/kg/day often adequate
›Grade III to IV: 2 mg/kg/day
›Do NOT exceed 2 mg/kg/day (no added benefit, increased harm)
›Upper GI only GVHD
›Methylprednisolone 0.5 to 1 mg/kg/day systemic
›Plus oral beclomethasone dipropionate 1 mg PO four times daily
›Plus oral budesonide 9 mg/day as adjunct
›Steroid taper
›Begin taper after clinical response confirmed
›Typical taper over 4 to 8 weeks minimum
›Avoid rapid taper to prevent flare
›Baseline immunosuppression escalation
›Continue calcineurin inhibitor at therapeutic levels
›Tacrolimus trough 5 to 15 ng/mL
›Cyclosporine trough 150 to 400 ng/mL
›Mycophenolate mofetil consideration
›1000 mg PO twice daily if not already on MMF
›Myelosuppression monitoring
Steroid-refractory GVHD treatment
›Definition of steroid-refractory aGVHD
›Progression on steroids within 3 days
›New organ involvement or worsening existing organ
›Grade escalation despite therapy
›No response after 5 to 7 days of systemic steroids
›No improvement in any involved organ
›Partial response criteria not met
›Ruxolitinib (JAK1/JAK2 inhibitor)
›First-line for steroid-refractory aGVHD
›Category 1 recommendation (NCCN)
›FDA-approved for steroid-refractory aGVHD age >= 12 years
›Dosing
›Ruxolitinib 10 mg PO twice daily
›Dose reduction for cytopenias: 5 mg twice daily
›Monitoring
›CBC weekly for first month then monthly
›Opportunistic infection risk (especially CMV reactivation)
›Lipid panel monitoring
›Alternative steroid-refractory agents
›Extracorporeal photopheresis (ECP)
›Particularly for skin-predominant GVHD
›Typically 2 sessions per cycle, biweekly cycles
›Vedolizumab
›Anti-alpha4-beta7 integrin for GI-predominant GVHD
›300 mg IV infusion at weeks 0, 2, 6, then every 8 weeks
›Infliximab
›TNF inhibitor for refractory GI or hepatic GVHD
›10 mg/kg IV every 1 to 2 weeks
›Infection risk including tuberculosis
›Mycophenolate mofetil if not already on regimen
›1000 mg PO twice daily
›Monitor CBC for myelosuppression
›Sirolimus
›2 mg PO daily loading then adjusted to trough 3 to 12 ng/mL
›TMA risk with concurrent calcineurin inhibitor
›Antithymocyte globulin (ATG) for refractory disease
›Rabbit ATG 1.5 mg/kg IV daily for 5 days
›High infection risk
›Clinical trial enrollment strongly encouraged for steroid-refractory disease
Remestemcel-L (pediatric indication)
›FDA-approved for steroid-refractory aGVHD in patients >= 2 months
›Mesenchymal stromal cell-based therapy
›2 million cells/kg IV infusion
›Two infusions per week for 4 weeks
›Monitoring
›Infusion reactions
›Efficacy assessment at week 4
›Infection prophylaxis on corticosteroids
›Pneumocystis prophylaxis
›Trimethoprim-sulfamethoxazole one single-strength tablet PO daily
›Dapsone 100 mg PO daily if sulfa allergy
›Antifungal prophylaxis
›Continue or intensify per institutional protocol
›Voriconazole or micafungin for high-risk patients
›CMV surveillance
›CMV PCR weekly in appropriate patients
›Preemptive ganciclovir or valganciclovir if threshold exceeded
›GI symptom management
›Octreotide for refractory secretory diarrhea
›100 to 500 mcg SC every 8 hours or IV infusion
›Ileus risk with high doses
›Loperamide for mild to moderate diarrhea
›4 mg PO initially then 2 mg after each loose stool
›Maximum 16 mg/day; avoid in colitis with fever
›Steroid side effect prevention
›Glucose monitoring daily
›Insulin therapy as needed for steroid-induced hyperglycemia
›Target blood glucose 6 to 10 mmol/l
›Bone protection
›Calcium 1200 mg PO daily in divided doses
›Vitamin D 1000 to 2000 IU PO daily
›Bisphosphonate for prolonged steroid courses > 3 months
›Proton pump inhibitor
›Pantoprazole 40 mg PO or IV daily
›Ulcer prophylaxis during high-dose steroid therapy