Chapter 58: Complications of Stem Cell Transplant

ACUTE GRAFT VS. HOST DISEASE (GVHD)^1,2

• Definition: Pro-inflammatory syndrome affecting the skin, liver, and gastrointestinal (GI) tract, typically within 100 days of hematopoietic stem cell transplant; immunocompetent transplanted cells mount an inflammatory response to cells in an immunosuppressed host.

  • Skin: Most commonly affected organ, commonly maculopapular eruption, can progress to bulla formation and epidermal necrosis

  • Gastrointestinal: Symptoms include watery diarrhea, severe abdominal pain, GI bleeding or ileus (endoscopy and biopsy are recommended for diagnosis when possible)

  • Hepatic: Cholestatic jaundice most common, but can progress to hepatic failure

  • See Table 58-1 for staging and grading of GVHD

• Therapy:

  • First-line therapy is corticosteroids (decrease inflammatory cytokines that propagate acute GVHD)

    • Skin GVHD typically responds most quickly to steroid therapy

  • Variety of second-line therapies include polyclonal (ATG) and monoclonal antibodies, TNF-blockade (infliximab, etanercept), and calcineurin inhibitors

  • Supportive care: Organ specific, including wound care, antimotility agents, bowel rest, ursodeoxycholic acid, and antimicrobial prophylaxis

VASOOCCLUSIVE DISEASE (VOD)/SINUSOIDAL OBSTRUCTION SYNDROME (SOS)^1–3

• Definition: Clinical syndrome of tender hepatomegaly, fluid retention, weight gain, and elevated serum bilirubin

  • Reported incidence varies from 5% to 60% of pediatric patients undergoing stem cell transplant

  • Poor prognosis with mortality rates as high at 90% in severe disease

• Diagnosis: Clinical diagnosis based on physical exam and laboratory findings. Liver ultrasound with Doppler is an adjunctive test but may be normal.

• Treatment:

  • Supportive care: Focus on fluid balance and preservation of renal blood flow, using fluid restriction, diuretics, dialysis

  • Defibrotide: Polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium

    • Bleeding is serious complication and requires frequent monitoring of platelet count and markers of coagulation

IDIOPATHIC PNEUMONIA SYNDROME^1,2

• Definition: Widespread alveolar injury following hematopoietic stem cell transplant in the absence of an active lower respiratory tract infection or cardiogenic causes

  • Spectrum of disease that includes interstitial pneumonitis, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, and bronchiolitis obliterans organizing pneumonia

    • Widespread alveolar injury: Multifocal infiltrates, ...