Stem cell transplant complications

Background

• Autologous or allogenic
• Cells harvested from bone marrow or peripherally
• Treats various malignant and benign heme/onc diseases
  • Leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome
  • Severe aplastic anemia and bone marrow failure, inherited blood dyscrasias or immune deficiencies
• Phases of recipient transplant process
  • Conditioning with radiation (usually total body) and/or chemotherapy
    • Goals: eliminate underlying malignancy, prevent rejection
  • Infusion
  • Neutropenic phase (weeks 2-4): no functioning immune system
  • Engraftment phase: highest risk of acute GVHD, lasts several weeks
  • Post-engraftment phase

Clinical Features/Differential

Neurologic complications

Higher risk with allogenic transplant

• Stroke
  • Median time of presentation 28 days post-transplant
  • Usually hemorrhagic due to thrombocytopenia
  • Can also be ischemic due infection, thrombosis, endocarditis
• Infection
  • Aspergillus (main cause), CMV, HSV, Toxoplasma, Candida, Cryptococcus, bacterial meningitis
• Metabolic Encephalopathy
  • Causes include hypoxemia, electrolyte abnormalities, metabolic acidosis, sepsis, hepatic failure, medications (sedatives and analgesics), thiamine deficiency

Cardiac complications

• Pulmonary edema
  • Risk factors: low EF, venooclussive disease, severe sepsis, anemia, high-dose chemo
• Pericardial effusion, pericardial tamponade
  • Rare, associated with cyclophosphamide toxicity, infection, chronic GVHD, renal failure

Pulmonary complications

• Engraftment syndrome
  • Due to rapid return of neutrophils
  • Features: fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy
• Diffuse alveolar hemorrhage
• Bronchiolitis obliterans with or without organizing pneumonia

GI complications

• Intestinal GVHD
  • abdominal pain, nausea/vomiting, diarrhea, GI bleeding +/- peritonitis, hepatitis, rash
• Pseudo-obstruction
• Veno-occlusive disease of liver
  • common
  • usually first 21 days after transplant
  • high dose chemo→endothelial damage of central hepatic venules→ thrombosis
  • RUQ pain, jaundice, weight gain
• GI bleed
  • Chemo, GVHD, or CMV/adenovirus → diffuse mucosal bleeding, ulcers, or necrosis

Renal complications

• Tumor lysis syndrome
• Hemorrhagic cystitis, veno-occlusive disease
• Hemolytic uremic syndrome

Graft-vs-host disease

• Acute (<100 days post-transplant) or chronic
• rash, mucositis, diarrhea, fever, +/- hepatitis, polyneuropathy, polymyositis, GI bleed, pancreatitis

Infection

See also neutropenic fever and Immunocompromised antibiotics

• Viral
  • CMV: pneumonitis most fatal, can also cause CNS infection, retinitis, hepatitis, pancreatitis, esophagitis, colitis
  • RSV
  • Adenovirus
  • HHV-6: pneumonitis, bone marrow suppression, enteritis, encephalitis
  • HSV: pneumonia, hepatitis, rash, encephalitis, DIC
• Bacterial
  • increased risk due to neutropenia, mucositis, skin fragility, GI problems, indwelling lines
  • Pseudomonas, klebsiella
  • MRSA, strep viridans, enterococcus
  • C. diff
  • Pneumonia, endocarditis, UTI, colitis, meningitis, etc.
• Fungal
  • Aspergillus: pulmonary, hepatic, endocarditis, CNS infection (main cause of CNS infection)
  • Candida: pneumonia, hepatic, CNS infection, endophthalmitis, esophagitis
  • Pneumocystis: pneumonia
  • Cryptococcus: CNS, pneumonia
• Toxoplasmosis: CNS infection, pneumonia
• Causative organisms by time after transplant:
  • early (<30 days): bacteria, candida, aspergillus, HHV, RSV
  • mid (30-100 days): CMV, PCP, adenovirus, HSV, aspergillus
  • late (>100 days): CMV

Treatment adverse effects

• Prednisone
  • Hyperglycemia, psychiatric symptoms, poor wound healing, edema, hypertension, ulcers
• Tacrolimus, cyclosporine
  • Neurotoxicity, tremor, hyperkalemia, nephrotoxicity, hypertension, hyperglycemia, gout, cardiotoxicity
• Mycophenolate mofetil, methotrexate
  • Cytopenias, GI distress
• Azathioprine
  • Cytopenias, pancreatitis, hepatitis
• Also consider toxicities related to other medications, including prophylactic or broad spectrum antibiotics

Evaluation

• CBC, BMP, Mg/Phos
• Low threshold for infectious workup
• Additional evaluation dependent on presentation

Management

• See immunocompromised antibiotics, neutropenic fever
• See thrombocytopenia, anemia
  • Patients should recieve leukocyte-reduced/irradiated PRBCs
• See Graft-vs-host disease
  • Treatment usually glucocorticoids
• Low threshold to consult heme/onc, infectious disease

Disposition

• Most complications will require admission

See Also

• Transplant complications
• Neutropenic fever, immunocompromised antibiotics
• Graft-vs-host disease
• Leukemia, lymphoma, multiple myeloma

References

Authors

Claire, Michael Holtz