@article {10852,
	title = {Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation.},
	journal = {Oncotarget},
	volume = {9},
	year = {2018},
	month = {2018 Apr 13},
	pages = {19543-19554},
	abstract = {<p>Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8{\textpm}100,3 μmol/g vs 28,4{\textpm}37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2{\textpm}48,8 μmol/g vs 55,7{\textpm}10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26\% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48\% vs 4\%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1\% vs 0,9\% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy. Based on our data, we suggest that TBI is detrimental for pancreatic functions, and speculate that DFO may contribute to the rapid pancreatic IO observed in these patients.</p>},
	issn = {1949-2553},
	doi = {10.18632/oncotarget.24646},
	author = {Maximova, Natalia and Gregori, Massimo and Simeone, Roberto and Sonzogni, Aurelio and Zanon, Davide and Boz, Giulia and D{\textquoteright}Antiga, Lorenzo}
}
@article {10853,
	title = {Vanishing Bile Ducts in the Long Term after Pediatric Hematopoietic Stem Cell Transplantation.},
	journal = {Biol Blood Marrow Transplant},
	volume = {24},
	year = {2018},
	month = {2018 Nov},
	pages = {2250-2258},
	abstract = {<p>There are no structured studies on liver histology after hematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinicopathologic features of liver disease in the long term after HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semiquantitative score evaluating inflammation, cholestasis, and ductopenia (bile ducts-to-portal tracts ratio <= .5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. We evaluated 131 biopsies taken in 50 HSCTs performed in 47 children (mean age, 9.7 {\textpm} 5.2 years). Pre-HSCT chemotherapy was administered in 36 of 50 (72\%). GVHD was diagnosed in 17 of 50 (34\%). Over time the overall score decreased from a mean of 6 {\textpm} 2.7 to 3.25 {\textpm} .96 (P < .01), inflammation from 1.22 {\textpm} 1.19 to 1 {\textpm} 0 (not significant), and cholestasis from 3.9 {\textpm} 2.08 to 1.5 {\textpm} .58 (P < .01). Ductopenia, found in 113 of 131 biopsies (93\%), worsened from .63 {\textpm} .35 to .16 {\textpm} .14 (P < .01). On multivariate analysis severe ductopenia (ratio <= .2) was associated with previous chemotherapy (P = .04), in particular with thiotepa, but not with history of GVHD. Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow-up will reveal whether these patients are prone to late liver-related morbidity and mortality.</p>},
	issn = {1523-6536},
	doi = {10.1016/j.bbmt.2018.07.009},
	author = {Maximova, Natalia and Sonzogni, Aurelio and Matarazzo, Lorenza and Ghirardi, Arianna and D{\textquoteright}Antiga, Lorenzo}
}
