Table 1 Hematopoietic stem cell transplantation-related endothelial injury syndromes

Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS)

2–60% [16, 17, 152, 153]

Triad of weight gain (often ascites), right upper quadrant pain or hepatomegaly, and elevated bilirubin [16, 17]

Fluid retention and ascites, jaundice, weight gain (≥ 5%), and painful hepatomegaly, in the absence of other identifiable causes of liver disease. Platelet transfusion refractoriness is an early sign, particularly in pediatric patients. Pediatric onset can present beyond 30 days after HSCT [17, 152]

100-day mortality (all causes): [17, 154] Mild VOD/SOS: 3% Moderate VOD/SOS: 20% Severe VOD/SOS: > 80%

Idiopathic pneumonia syndrome (IPS)/ diffuse alveolar hemorrhage (DAH)

2–14% [19]

Signs and symptoms of diffuse or multilobar pneumonia, with evidence of alveolar injury, after infectious causes have been ruled out by bronchoscopy or lung biopsy [19]

IPS: Shortness of breath, cough, hypoxemia, with or without fever. May progress rapidly to ARDS/hypoxemic respiratory failure requiring intubation. Onset usually within 120 days after HSCT [19, 155]

DAH: Fever, dyspnea, and hypoxemia; occurs within 30 days after HSCT and within 5 days of neutrophil engraftment [19]

Mortality: [18] Overall: 60–86% Patients requiring mechanical ventilation: > 95%

Engraftment syndrome (ES)

13% [157]

Major: noninfectious fever, erythroderma > 25% of body surface, noncardiogenic pulmonary edema

Minor: hepatic dysfunction, renal insufficiency, weight gain, transient encephalopathy [3, 156]

Fever, generalized rash, shortness of breath. Usually transient and improves quickly with steroids [156]

Mortality: 18% [156]

Capillary leak syndrome (CLS)/ fluid overload

CLS: 5% [22]

Overall fluid overload: 43–66%; Grade ≥ 2 fluid overload:

6–21% [5]

Weight gain, general edematous syndrome that does not respond to furosemide treatment [3]

CLS: Pulmonary edema, total body volume overload with weight gain, but relative intravascular volume depletion [156]

Fluid overload: Fluid retention, weight gain [5]

Mortality: [156] CLS in combination with other EIS: 60% 100-day nonrelapse mortality: [5] Overall fluid overload: 5–9% Grade ≥ 2 fluid overload: 30–36%

Graft-versus-host disease (GVHD)

40–80%

Grade II to IV GVHD [158]

Chronic GVHD: Diagnosis based on either the presence of specific diagnostic signs or distinctive signs in at least one target organ (skin and appendages, mouth, eyes, genitalia, esophagus, lungs, muscles, and fascia) and by additional confirmation (e.g., biopsy or other objective diagnostic test) [159]

Acute GVHD: Skin: inflammatory maculopapular erythematous skin rash

Liver: elevated bilirubin

GI tract: anorexia with weight loss, nausea, vomiting, diarrhea, severe pain, GI bleeding and/or ileus

Chronic GVHD may involve: skin, nails, scalp and body hair, mouth, eyes, esophagus, lungs, muscles, joints and fascia, genitalia [159]

Overall mortality: [12] Acute GVHD: 16% Grade IV GVHD: 92%

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA)

Adults: 4–68% [8, 30,31,32,33,34,35,36]

Pediatrics: 3–39% [24, 27,28,29]

Overlapping criteria from diagnostic algorithms: schistocytosis, increase in serum LDH levels, thrombocytopenia, anemia, or negative Coombs test

Additional criteria: proteinuria, hypertension, terminal complement assay results [3]

Hemolytic anemia with evidence of microangiopathy. Acute renal dysfunction, proteinuria, uncontrolled hypertension. Neurologic dysfunction, encephalopathy, seizures. May also involve lungs leading to pulmonary vascular hypertension, respiratory failure. Intestinal TMA leads to intestinal ischemia, pain, and lower GI bleeding [3, 8, 29]

Non-relapse mortality: [29, 160] Moderate TMA: 34–44% Severe TMA: > 90%