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Table 1 Hematopoietic stem cell transplantation-related endothelial injury syndromes

From: Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy

Syndrome Incidence Diagnostic criteria Clinical presentation Clinical outcomes
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%
  1. ARDS Acute respiratory distress syndrome, CLS Capillary leak syndrome, DAH Diffuse alveolar hemorrhage, ES Engraftment syndrome, GI Gastrointestinal, GVHD Graft-versus-host disease, HSCT Hematopoietic stem cell transplantation, HSCT-TMA Hematopoietic stem cell transplantation-associated thrombotic microangiopathy, IPS Idiopathic pneumonia syndrome, LDH Lactate dehydrogenase, TMA Thrombotic microangiopathy, VOD/SOS Veno-occlusive disease/sinusoidal obstruction syndrome