stem cell transplant complications

The Allogeneic Timeline

Time from transplant is the single most useful diagnostic filter.

Phase	Time	Key Risks
Pre-Engraftment	Days 0–30	Mucositis, Bacterial Sepsis, Haemorrhagic Cystitis, VOD/SOS
Early Post-Tx	Days 30–100	Acute GVHD, CMV/EBV, Engraftment Syndrome, TA-TMA
Late Phase	Days >100	Chronic GVHD, Encapsulated bacteria, VZV, Secondary Malignancy

infectious complications

clinical pearl

Fever is often absent due to high-dose corticosteroids. Maintain low threshold for septic workup in “unwell” patients.

• Bacterial:
  • Mucositis: Portal for Gram-positive (Strep. viridans) and anaerobes.
  • Late Phase: Hypogammaglobulinemia/functional asplenia $\to$ Strep. pneumo risk.
• Viral:
  • CMV: Major cause of pneumonitis/colitis.
    • Prophylaxis: Letermovir (Standard of care for seropositive recipients).
    • Treatment: Ganciclovir or Valganciclovir.
  • BK Virus: Causes Haemorrhagic Cystitis (dysuria, haematuria). Differentiate from cyclophosphamide toxicity (Mesna prevention).
  • VZV: Reactivation common late. Prophylaxis required >1 year.
• Fungal/PJP:
  • PJP: Cotrimoxazole required for ≥6 months or while on immunosuppression.
  • Invasive Fungal: Fluconazole/Posaconazole prophylaxis during neutropenia/GVHD.

non-infectious acute complications

1. vascular & endothelial

• VOD/SOS (Veno-Occlusive Disease):
  • Triad: RUQ pain + Weight gain (fluid retention) + Jaundice (hyperbilirubinaemia).
  • Rx: Defibrotide (strict funding criteria).
• TA-TMA (Transplant-Associated Thrombotic Microangiopathy):
  • Presentation: Coombs-neg haemolysis, schistocytes, thrombocytopenia, renal failure, HTN.
  • Diagnosis: Normal ADAMTS13 (vs TTP). Screen if $\ge$ 3 features present.
  • Trigger: CNI toxicity, viral reactivation.
• Engraftment Syndrome:
  • Timing: Within 4 days of neutrophil recovery (typ. Day +10 to +20).
  • Clinical: Non-infectious fever + rash + pulmonary oedema (“capillary leak”).
  • Rx: Pulse steroids.

2. organ toxicities

• Cardiovascular:
  • Arrhythmias: AFib/Flutter common.
  • Cardiomyopathy: High-dose Cyclophosphamide is cardiotoxic (acute HF, haemorrhagic myocarditis).
• Neuro (CNI Toxicity):
  • Cyclosporine/Tacrolimus cause PRES, tremors, seizures.
  • Pearl: Hypomagnesaemia drastically lowers seizure threshold—aggressive Mg replacement required.

graft-vs-host disease (gvhd)

exam trap

Distinguishing Acute vs Chronic is based on clinical features, not the rigid “Day 100” cutoff.

acute gvhd

• Patho: Donor T-cells attack host tissues.
• Classic Triad:
  1. Skin: Maculopapular “sunburn” rash (acral/palmar/plantar).
  2. Gut: High volume secretory diarrhoea (green/mucoid, often >1L/day).
  3. Liver: Cholestatic jaundice (High ALP/Bili).
• Management:
  • Systemic: Methylprednisolone 1–2 mg/kg IV.
  • Refractory: Ruxolitinib (JAK1/2 inhibitor).

chronic gvhd

• Patho: Fibrotic/Autoimmune phenotype.
• Presentation: Scleroderma-like skin, Bronchiolitis Obliterans (air trapping), Sicca (dry eyes/mouth).
• Grading: Mild/Moderate/Severe based on number of organs and functional impairment.
• Management: Steroids + CNI taper + supportive care.

survivorship & maintenance

• Vaccination: Immune “amnesia”. Restart inactivated vaccines at 6–12 months. Live vaccines (MMR/Varicella) delayed ≥24 months (and only if no active GVHD).
• Metabolic: Monitor for metabolic syndrome (HTN, DM, Dyslipidaemia).
• Malignancy: Increased risk of secondary solid tumours (skin, oral, thyroid) and MDS/AML.