Capillary Leak Syndrome in the Pediatric Population: Incidence, Risk Factors and Prognostic VALUE

Capillary leak syndrome (CLS) is complication occurring after stem cell transplantation (SCT), which consists in a loss of intravascular fluids into interstitial spaces after endothelial damage. CLS incidence is around 20% among adults, and so far unknown in the pediatric population. Risk factors for CLS are the use of G-CSF as well as the burden of pre-transplant chemotherapy.  We aimed at assessing CLS incidence, risk factors and impact on survival in a pediatric cohort of patients.

In this single centre, retrospective study we revised the clinical charts of all the patients <18 years of age undergoing SCT between January 2002 and May 2012 at our Institution.

CLS was defined by at least the first 2 of the following criteria: weight gain >3% in 24 hours, positive intake balance irrespective of diuretic administration, oedemas (ascites, pleural effusion, pericarditis, peripheral oedema), hypotension (10% reduction of MAP), hypoalbuminemia

Clinical data were collected in an electronic database.

235 patients underwent 276 SCT procedures in the analyzed timeframe.

15/276 fulfilled criteria for CLS diagnosis (5.4%).

Patients´ characteristics, conditioning regimen, donor type, stem cell source, CSA administration as GvHD prophylaxis and G-CSF administration did not represent a risk factor for CLS.

The probability of developing CLS was significantly higher in patients exhibiting sepsis (14.3% vs 0.6 %,p< 0.01), and patients developing CLS were at higher risk for developing acute GvHD in the first 30 days after SCT (10.8% vs 1.8% p<001).

10/15 patients exhibiting CLS required intensive care treatment.

In 9 patients CLS did not resolve and directly led to death.

CLS deeply impacts on overall survival on day + 100 after transplantation (pOS 92.3% vs 57.1%, p<0.01), being a strong predictive factor for day + 100 TRM.

The CLS is an uncommon but severe complication in pediatric SCT recipients.

No pre-transplant risk factors for CLS could be identified in our study. Among the post transplant complications, sepsis is significantly associated with the appearance of CLS. Patients who develop CLS often need an intensive care treatment and are at high risk for early TRM, as well as for other endothelium derived complications like GvHD.

The biological relation between sepsis, GvHD and CLS development in terms of cytokine release and endothelial damage is worth further studies in order to possibly support new targeted therapies.