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The gastrointestinal (GI) tract is one of the systems most commonly affected by transplant complications. It is due to the high vulnerability of the gut mucosa composed of dividing cells, which are susceptible to chemotherapy-induced damage, rich vasculature, constant contact with intestinal microflora, and high content of immune-competent cells.
The gastrointestinal (GI) tract is one of the systems most commonly affected by transplant complications. It is due to the high vulnerability of the gut mucosa composed of dividing cells, which are susceptible to chemotherapy-induced damage, rich vasculature, constant contact with intestinal microflora, and high content of immune-competent cells. Therefore, when evaluating symptoms from the GI system, various possible causes must be taken into account, especially drug toxicity, infections, and graft-versus-host disease. In this chapter selected GI complications most frequent after HSCT will be presented. The GI aGVHD was already discussed in Chaps. 43 and 44 and infectious causes in Chaps. 38 and 39.
Nausea: a disorder characterized by a queasy sensation and/or the urge to vomit.
Vomiting: a disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Acute onset: within 24 h of chemotherapy administration (peak at 4–6 h) lasting for 24–48 h.
Delayed onset: occurs more than 24 h after chemotherapy (peak at 2–3 days) lasting for prolonged period of time.
Direct activation of the vomiting center in the brain stem by chemotherapy, which triggers target organs in GI tract.
Damage to the GI mucosa, causing vagal stimulation and neurotransmitter (serotonin, neurokinin-1, dopamine) release causing reflexive stimulation of the vomiting center.
Radiotherapy-induced neurotransmitter release stimulating vomiting center concomitant with brain edema.
Induced directly by conditioning chemoradiotherapy
TBI, TLI, cranio-spinal irradiation
Chemotherapy drugs (NCCN 2017):
• High emetic risk (frequency > 90%): CY >1500 mg/m2, BCNU >250 mg/m2
• Moderate emetic risk (frequency 30–90%): bendamustine, BU, BCNU ≤250 mg/m2, CY ≤1500 mg/m2, MEL
• Minimal to low emetic risk (frequency < 30%): VP, TT, FLU, MTX ≤50 mg/m2
Drugs: opioids, CNI, nystatin, AmB, voriconazole, itraconazole, TMP-SMX, MMF
Hepatic disease: GVHD, VOD, viral hepatitis
Infection: CMV, HSV, VZV, fungal, bacterial, norovirus, rotavirus, parasites
Based on symptoms.
50.2.6 Grading (CTCAE v4.0 [NCI 2009])
Loss of appetite without alteration of eating habits
Oral intake decreased without significant weight loss, dehydration, or malnutrition
Inadequate oral caloric or fluid intake, tube feeding, TPN, or hospitalization indicated
1–2 episodes (separated by 5 min) in 24 hs
3–5 episodes (separated by 5 min) in 24 h
≥6 episodes (separated by 5 min) in 24 h, tube feeding, TPN, or hospitalization indicated
Life-threatening consequences, urgent intervention indicated
Prevention of nausea/vomiting is the mainstay of clinical management since treatment frequently proves ineffective. Delayed nausea should be treated with scheduled antiemetics for 2–4 days after completion of chemotherapy.
High emetic risk
Serotonin (5-HT3 antagonist) (patients should be monitored for QT corrected prolongation)
• Short-acting: ondansetron 3 × 8 mg IV on days of chemo +24–48 h, granisetron, dolasetron
• Long-acting: palonosetron 0.25 mg IV, may be repeated every 3 days
Neurokinin-1 receptor antagonists, e.g., aprepitant
Dexamethasone 2–10 mg IV (as required for a short duration)
Moderate emetic risk
Serotonin (5-HT3) antagonists (as above)
Dexamethasone 2–10 mg IV
Low emetic risk
Serotonin (5-HT3) antagonists (short acting, as above)
Serotonin (5-HT3) antagonists (short- or long-acting, as above)
Dexamethasone (4 mg/d or 4 mg bid)
50.2.9 Other Nausea/Vomiting
Addition of a different class anti-emetic drug
Prochlorperazine (10 mg IV q6h)
Haloperidol (1–2 mg q4h)
Metoclopramide (0.5–2 mg/kg IV q6h)
Scopolamine transdermal patch
Prevention of nausea/vomiting by efficient prophylaxis at every treatment
Strong smell avoidance
A disorder characterized by frequent and watery bowel movements.
Depending on the cause.
Chemotherapy and radiation therapy-related toxicity
– Clostridium difficile
– Viral (CMV, VZV, rotavirus, norovirus, astrovirus, adenovirus)
– Parasitic (giardia, strongyloides, cryptosporidium)
– Fungal (candida)
Medications (antibiotics, mycophenolate mofetil, oral nutritional supplements)
Other: pancreatitis/pancreatic insufficiency, lactose intolerance/disaccharidase deficiency, malabsorption, inflammatory bowel disease, liver and gallbladder disease
Stool examination and microbiological workup
• C. difficile toxin, antigen, culture
• Parasites (giardia, strongyloides, cryptosporidium)
• Viruses (CMV, VZV, rotavirus, norovirus, astrovirus, adenovirus)
• Fungi (culture)
Sigmoidoscopy/colonoscopy ± gastroscopy
• Histopathology for GVHD, cryptosporidium, and CMV
• Viral, parasitic/bacterial cultures
Biochemistry (triglycerides, amylase, lipase),
Ultrasound, CT (in GVHD distal ileum or proximal colon most likely involved)
Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
Increase of 4–6 stools per day over baseline; moderate increase in ostomy output compared to baseline
Increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self- care activities of daily living
Life-threatening consequences; urgent intervention indicated
Targeted, according to the known or suspected cause, consider overlap with another pathology (e.g., aGVHD with gut CMV infection)
Ancillary: modification of diet
• Lactose- or gluten-free
• Restricted diet (low roughage, low residue, low or no lactose)
• Temporarily nothing per os and TPN
Avoid fluid loss and dyselectrolytemia
Monitor and replace protein losses (albumin, gamma globulin)
Loperamide 2–4 mg p.o. every 6 h if associated with toxicity of conditioning or GVHD
Heartburn and/or epigastric pain observed most frequently during conditioning and period of mucositis.
Mucositis, medications, altered gastric pH, peptic ulcer disease, and fungal esophagitis.
Based on clinical symptoms ± endoscopy.
Depending on the cause, elevation of the head of bed, and consideration of proton pump inhibitors and other symptomatic treatments (e.g., alginate, antacid, and topical local anesthetics, such as oxetacaine for mucositis). May require systemic analgesia if patient unable to swallow.
50.5 GI Bleeding
May appear as melena, hematemesis or bloody stool, or emergence of normocytic anemia.
Thrombocytopenia, esophageal trauma, esophagitis, colitis, anal fissures or varices, viral infections, GVHD, and plasma coagulation impairment.
Esophagogastroduodenoscopy, colonoscopy, and angioCT.
Treatment of underlying disorder
• Platelet transfusion to >50 × 109/L
• RBC transfusion
• Fresh frozen plasma, fibrinogen concentrates, vitamin K supplementation
• Endoscopic cauterization or embolization
When massive blood loss
• Tranexamic acid
• Recombinant factor VII
Necrosis of usually large intestinal wall associated with chemotherapy toxicity and bacterial overgrowth.
Occurs within 30 days after HSCT, patients usually complain of pain in right lower abdominal quadrant, often with associated fever.
Additionally, nausea, emesis, increased abdominal wall tension, and watery bloody diarrhea may occur (Robak et al. 2017).
Clinical and abdominal ultrasound or CT: bowel wall thickening usually limited to single region, e.g., ileocecal or ascending colon; may be associated with perforaton and air within intestinal wall.
Antibiotics and bowel rest. Avoid surgical intervention.
50.7 Pancreatic Disease
Pancreatic insufficiency and atrophy or acute pancreatitis.
Medications (prednisone, tacrolimus), stones, and pancreatic GVHD.
Insufficiency and atrophy: low serum trypsinogen, high fecal elastase-1, and possible atrophy in imaging. Acute pancreatitis: elevated lipase and amylase, elevated fecal fat, and edema in ultrasound/CT.
When insufficiency: enzyme replacement.
50.8 Chronic Esophageal GVHD
Barium meal: mid/upper esophageal strictures, webs, rings, bullae, and desquamation. Endoscopy: as above, erythematous, friable sloughed mucosa.
When severe and chronic, need serial dilations and enteral tube placement or esophagectomy.
Nausea/vomiting or diarrhea occurring before engraftment is most likely caused by toxicity of conditioning, while after engraftment, GVHD needs to be considered, especially in allo-HSCT setting.
For the whole post transplant period, infectious causes should also be considered with bacterial or fungal causes predominating in the neutropenic period and viral reactivations/infections in the later phases.
Importantly, inflammation caused by infection may become a trigger to GVHD, while GVHD is frequently followed by infection; therefore, overlapping scenarios always need to be taken into account.
GI GVHD is frequently a diagnosis of exclusion (especially in patients with other overlapping causes which may impact on laboratory investigations). However, it should always be considered when symptoms persist despite extensive workup and/or directed treatment.
- Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Published: May 28, 2009 (v4.03: June 14, 2010) U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Antiemesis. Version 2.2017. March 28, 2017. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf
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