Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

Table 1 Emetogenic potential of chemotherapeutic agents used in stem cell transplantation

	Chemotherapeutic agent
High (90%) emetogenic risk	Carmustine > 250 mg/m2
	Cyclophosphamide > 1500 mg/m2
Moderate (30%-90%) emetogenic risk	Busulfan
	Cytarabine > 200 mg/m2
	Melphalan
Low (10%-30%) emetogenic risk	Etoposide
Minimal (< 10%) emetogenic risk	Fludarabine
	Rituximab

Table 2 Differential diagnosis of post-transplant diarrhea

Conditioning regimen-related
Acute GVHD
Drug toxicity
	Antibiotic-related
	Opioid withdrawal
	Mycophenolate mofetil toxicity
	Tacrolimus (thrombotic microangiopathy)
	Proton pump inhibitors
	Promotility agents
	Magnesium salts
	Metoclopramide
Infectious
	Clostridium difficile
	CMV
	Rotavirus
	Adenovirus
	EBV
	HSV
	Astrovirus
	Norovirus
	Bacterial infections including ESBL
	Fungal infections
	Parasitic infections (Cryptosporidium, Microsporidia, Giardia)
	Mycobacterial infections
Others
	Lactose intolerance
	Malabsorption
	Pancreatic insufficiency

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; HSV: Herpes simplex virus; GVHD: Graft-versus-host disease; ESBL: Extended spectrum β lactamase.

Table 3 Staging of acute graft-versus-host disease (modified Keystone criteria)

Stage	Intestinal tract	Liver	Skin
0	Diarrhea ≤ 500 mL/d	Bilirubin < 2.0 mg/dL	No rash
1	Diarrhea 501-1000 mL/d or nausea (± vomiting)	Bilirubin 2.0-3.0 mg/dL	Maculopapular rash < 25% of body surface
2	Diarrhea 1001-1500 mL/d	Bilirubin 3.1–6.0 mg/dL	Maculopapular rash 25%-50% of body surface
3	Diarrhea > 1501 mL/d	Bilirubin 6.1–15 mg/dL	Generalized erythroderma
4	Severe abdominal pain +/- ileus	Bilirubin > 15 mg/dL	Generalized erythroderma with blister/bullous formation and desquamation

Table 4 Grading of acute graft-versus-host disease (modified Keystone criteria)

Grade	Gut	Liver	Skin
0 (none)	0	0	0
I(mild)	0	0	1-2
II (moderate)	1	1 or	3 or
III (severe)	2-4	2-3 or	0-3
IV (life-threatening)		4	4 or

Table 5 Differential diagnosis for liver function abnormalities after hematopoietic stem cell transplantation

First 3 wk post-transplant

Drug toxicity

Conditioning regimens (cyclophosphamide, total body irradiation, bis-chloroethylnitrosourea, busulfan)

Calcineurin inhibitors

Azole antifungals

SOS

Sepsis, candidiasis

Ischemic liver disease

From 3 wk to 3 mo post-transplant

Acute GVHD

Drug toxicity

SOS

Hepatitis (fulminant, acute or chronic):

Viral (HBV, HCV, HSV, VZV, adenovirus) reactivation

Bacterial or fungal Infection

Fungal abscess

Gall bladder disease/cholecystitis

Hyperalimentation

Post-transplant lymphoproliferative disorder (EBV-related)

After 3 mo post-transplant

Chronic GVHD

Iron overload

Chronic viral hepatitis

Drug toxicity

Liver fibrosis or cirrhosis:

SOS

Viral infections

Hemosiderosis

Disease recurrence or new malignancy including hepatocellular carcinoma, lymphoproliferative disorder

Nodular regenerative hyperplasia

Gallbladder disease

GVHD: Graft-versus-host disease; SOS: Sinusoidal obstruction syndrome; EBV: Epstein-Barr virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HSV: Herpes simplex virus; VZV: Varicella zoster virus.

Table 6 Risk factors for sinusoidal obstruction syndrome

Existing liver disease:

Chronic viral hepatitis

Alcohol related hepatitis

Steatohepatitis

Cirrhosis, lobular fibrosis

Cholestatic disorders

Extramedullary hematopoiesis with sinusoidal fibrosis

Prior history of:

SOS

Extensive chemotherapy and stem cell transplantation

Hepatic radiation

Drugs

Recent gemtuzumab ozogamicin use

Conditioning agents:

High dose TBI (> 14 Gy)

Cyclophosphamide metabolite: acrolein

Busulfan

Melphalan

Concomitant use of sirolimus during conditioning

SOS: Sinusoidal obstruction syndrome; TBI: Total body irradiation.