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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

TABLE 58-1

Staging and Grading of Graft vs. Host Disease (GVHD)

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TABLE 58-1

Staging and Grading of Graft vs. Host Disease (GVHD)
Skin Gastrointestinal (GI) Liver
Stage
1 <25% skin surface Diarrhea 10–19.9 mL/kg/day or persistent nausea, vomiting or anorexia, with a positive upper GI biopsy Bilirubin 2–3 mg/dL
2 25%–50% skin surface Diarrhea 20–30 mL/kg/day Bilirubin 3.1–6 mg/dL
3 >50% skin surface Diarrhea >30 mL/kg/day Bilirubin 6.1–15 mg/dL
4 Generalized erythroderma with bullae formation Severe abdominal pain with or without ileus Bilirubin >15 mg/dL
Grade
I Stages 1–2 None None
II Stage 3 or Stage 1 or Stage 1
III - Stages 2–4 or Stages 2–3
IV Stage 4 - Stage 4

Grade II requires Stage 3 Skin or Stage 1 GI or Stage 1 Liver

Grade III requires Stage 2–4 GI or Stage 2–3 Liver

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 SYNDROME1,2

  • 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 ...

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