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

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

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

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

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

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

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

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

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

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