1. Immunosuppression De-Escalation Protocols

Once acute GVHD signs (e.g., rash, diarrhea, bilirubin) show a sustained improvement of ≥50% over 7–14 days on high-dose steroids, a gradual taper can begin. The goal is to balance the risk of a GVHD flare against the significant toxicities of prolonged immunosuppression.

A. Corticosteroid Tapering

The initial induction dose is typically prednisone 1–2 mg/kg/day (or its methylprednisolone equivalent), with higher doses reserved for grade IV GVHD. The subsequent taper schedule depends on the initial severity.

B. Calcineurin Inhibitor (CNI) Reduction

Tacrolimus or cyclosporine levels should be maintained at therapeutic targets during the initial steroid taper. Reductions are considered only after the GVHD is quiescent and steroids are at a lower dose.

• Tacrolimus: From a target trough of 5–10 ng/mL, reduce by 2 ng/mL every 1–2 weeks.
• Cyclosporine: From a target trough of 100–200 ng/mL, reduce the target by approximately 20% with each step.
• Toxicity Management: If serum creatinine increases by >50% or neurotoxicity occurs, reduce the CNI dose by 25% and evaluate for alternatives. In patients on CRRT, tacrolimus clearance is increased, often requiring a ~50% higher daily dose with close therapeutic drug monitoring (TDM).

C. Monitoring for Flare vs. Over-Suppression

Vigilant monitoring is critical during the taper. Distinguishing a GVHD flare from infection is a key clinical challenge.

• GVHD Flare Signs: New or recurrent rash, onset of secretory diarrhea, or a rise in bilirubin ≥2 mg/dL over 48 hours.
• Over-Suppression Signs: Unexplained fever, neutropenia, CMV or EBV viremia, or invasive fungal infections.
• Surveillance Labs: CBC twice weekly, LFTs weekly, and CMV/EBV PCR weekly are standard during the active taper phase.

2. IV-to-Enteral Conversion Strategies

Transitioning from intravenous (IV) to enteral (PO) immunosuppressants is a critical step toward discharge. This should only occur once GI function is restored, hemodynamics are stable, and the patient’s mental status permits. Careful dose conversions and early TDM are essential to prevent under- or over-exposure.

A. Equivalent Formulations & Conversions

B. Feeding Tube & Drug-Nutrient Interactions

• Tube Material: Use silicone-lined feeding tubes for tacrolimus, as PVC plastic can bind the drug and reduce delivery.
• Flushing Protocol: Flush the tube with ≥20 mL of water before and after each medication administration. Document flush volumes meticulously.

C. Absorption Monitoring

After converting, verify absorption with TDM. Check a tacrolimus trough level 24 hours after the first enteral dose, adjusting the dose to maintain the target of 5–10 ng/mL. If GVHD signs persist despite “therapeutic” levels, investigate potential malabsorption or non-adherence.

3. Post-ICU Syndrome (PICS) Mitigation

Patients recovering from severe GVHD are at high risk for Post-ICU Syndrome (PICS), a constellation of new or worsened cognitive, physical, and psychological impairments. Proactive, multidisciplinary interventions are key to reducing long-term morbidity.

A. Risk Stratification and Screening

Patients with an ICU stay >7 days, high sedation requirements, or multiorgan failure are at highest risk. Screen for PICS before discharge using validated tools:

• Cognition: Mini-Cog test.
• Physical Function: 6-minute walk test or Short Physical Performance Battery.
• Mental Health: Hospital Anxiety and Depression Scale (HADS) or PHQ-9.

B. Delirium Prevention and Early Mobility

The ABCDEF bundle is a proven, evidence-based framework for improving ICU outcomes and reducing the incidence of PICS.

C. Psychological Support

Screen for PTSD (Impact of Event Scale) and depression (PHQ-9) before discharge. Provide referrals to psycho-oncology or transplant psychiatry services for ongoing counseling and therapy. Educating the family on PICS symptoms and coping strategies is also crucial for long-term recovery.

4. Medication Reconciliation and Discharge Counseling

A comprehensive medication reconciliation process and thorough patient/caregiver education are the cornerstones of a safe transition to outpatient care, directly impacting readmission rates and long-term outcomes.

A. Reconciliation Template

A standardized discharge checklist should include:

1. Immunosuppressants: Document the current dose and the full taper schedule for steroids. Clearly list the CNI name, dose, and trough goal, along with any adjunct agents (e.g., MMF, sirolimus).
2. Antimicrobial Prophylaxis: Confirm continuation of prophylaxis for PJP (TMP-SMX), herpes viruses (acyclovir/valacyclovir), and fungal pathogens (posaconazole or fluconazole).
3. Supportive Medications: List all GI protectants, bone health agents, antihypertensives, and antidiabetic medications.
4. Allergies & ADRs: Re-verify all allergies and document any adverse drug reactions experienced during the admission.

B. Patient and Caregiver Education

Focus education on practical skills and red-flag symptoms:

• Warning Signs: Teach how to identify early signs of a flare: new rash, pruritus, ≥3 watery stools/day, jaundice, new mouth ulcers, or fever.
• Adherence Tools: Provide tools like pillboxes and demonstrate how to set phone alarms. Link medication times to daily routines (e.g., meals).
• Side-Effect Management: Discuss common side effects and their management, such as taking antiemetics for nausea or performing regular glucose monitoring for steroid-induced hyperglycemia.

C. Outpatient Handoff and Follow-Up

A successful discharge requires seamless communication and planning:

• Schedule a follow-up transplant/GVHD clinic visit within 7–14 days post-discharge.
• Transmit the full MAR and taper plan to the outpatient pharmacy and nursing teams.
• Conduct a warm, verbal handoff between the inpatient pharmacist and the outpatient care coordinator.
• Arrange for home health services if needed for TDM draws or infusion therapy.
• Confirm insurance coverage for high-cost medications and complete prior authorizations before discharge.