The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

This is the first demonstration that functionally assessed ED is present in ALL children at the diagnosis and results from elevated ADMA and parallel inflammatory ED.

SummaryBackgroundThe aim of the study was to analyse MR images of the brain, including advanced MR techniques, such as single voxel spectroscopy (MRS) and diffusion tensor imaging (DTI), in children with X-linked adrenoleukodystrophy (X-ALD) before and after haematopoietic stem cell transplantation (HSCT) and to establish the imaging criteria which may be helpful in the assessment of disease staging, qualification to HSCT and follow-up.Material/MethodsSeven boys, aged 5–10 years, (mean 8.14 years) with biochemically proved X-ALD, underwent plain MR imaging with a 1.5 T unit before and after HSCT. Structural images were analyzed using an MRI severity scale (Loes scale). In one patient the follow-up examinations included MRS with the assessment of metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr), as well as DTI with evaluation of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in several white matter tracts.ResultsTwo boys had an MRI severity score before HSCT equal to <8 points, and after HSCT they showed no clinical or radiological progression. In 5 patients with a higher severity score (from 8 to 16 points, mean 10.9) before HSCT, clinical and radiological progression was observed (MRI severity score from 17 to 25 points, mean 20.9). Follow-up advanced MRI techniques in one boy showed metabolic alterations, as well as decreased FA and ADC values in all evaluated areas.ConclusionsChildren at an early stage of X-ALD (below 8 points in MRI severity scale) are more likely to benefit from HSCT. DTI and MRS seem to be more useful imaging methods to assess the progression of X-ALD.

5314 Background: Activation of endothelium has been demonstrated to be associated with an increased risk of mortality in severe diseases. In this study we hypothesize that ALL might be also associated with endothelial dysfunction (ED) and that children with concomitant ED might be at higher risk for death. Methods: N=18 children at age of 4–18 years with ALL treated with the ALLIC protocol were investigated. Plasma levels of markers of ED (VCAM-1, ICAM-1, E-selectin, P-selectin and PAI-1), lipid peroxidation (malonyldialdehyde – MDA), angiogenesis (VEGF) as well as routine blood tests were analyzed at baseline – the day of diagnosis of ALL, next during the 33rd day of the protocol (steroid therapy, evaluation of remission) and subsequently at the 78th day of therapy (beginning of the protocol M). The control group constituted of N=15, age-matched healthy children. Results: Children with ALL were characterized with significantly worse kidney and liver function at baseline as compared to the control. Similarly, the fasting glycemia was higher in the investigated group. Markers of endothelial proagreagattory and procoagulative function (P-selectin and PAI-1) were similar in both groups at baseline. However, vascular inflammation was significantly more pronounced in children with ALL at baseline as compared to the healthy control (ICAM-1= 467.1±72.8 vs. 206.3±21.7 ng/ml, p<0.05). High baseline plasma level of E-selectin and VEGF (as compared to the healthy control) were positive predictors for death in children with ALL (E-selectin: 56.1±10.9 vs. 28.1±10.0 ng/ml, respectively; VEGF: 366.1±61.6 pg/ml vs. 190.1±71.4 pg/ml, respectively, p<0.05). Conclusion: Endothelial inflammatory activation is a common phenomenon in children with ALL. High baseline level of VEGF and E-selectin are associated with higher mortality in ALL. Disclosures: No relevant conflicts of interest to declare.