Maximova Natalia, Gregori Massimo, Simeone Roberto, Sonzogni Aurelio, Zanon Davide, Boz Giulia, D'Antiga Lorenzo
Bone Marrow Transplant Unit, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Department of Pediatric Radiology, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Oncotarget. 2018 Apr 13;9(28):19543-19554. doi: 10.18632/oncotarget.24646.
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±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±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.
尽管许多研究探讨了造血干细胞移植(HSCT)后器官功能障碍的风险,但在这种情况下胰腺的易感性却知之甚少。我们旨在研究铁过载(IO)和全身照射(TBI)对接受HSCT的儿童胰腺功能的影响。我们回顾性评估了2012年至2016年间入院的符合以下标准的儿童:胰腺铁浓度(PIC)正常、HSCT前胰腺功能正常、有采用梯度回波序列的腹部磁共振成像以及HSCT前和出院时全套IO和胰腺功能的生化标志物。我们根据预处理方案中是否使用TBI或清髓性化疗(MCHT)对患者进行分组。所有有严重IO或中度IO且有植入延迟或移植相关并发症高风险的患者从预处理第一天至出院接受去铁胺(DFO)螯合治疗。研究期间有63例患者接受了HSCT,13例不符合纳入标准;50例(每组25例)纳入分析,且在基线评估时未显示出差异。在随访检测中,TBI组的PIC显著更高(107.8±100.3 μmol/g,而MCHT组为28.4±37.9,p<0.0001)。在TBI组中,接受DFO治疗的患者PIC更高(223.2±48.8 μmol/g,未接受DFO治疗的为55.7±10.5,p<0.0001),且随访时所有PIC>100 μmol/g的患者都接受了基于DFO的螯合治疗,而PIC较低的患者中这一比例为26%(p<0.0001)。移植后1个月出现外分泌性胰腺功能障碍的患者数量在TBI组显著更高(48%对4%;p<0.0001)。TBI组胰腺体积的平均减少显著更大(39.1%对MCHT组的0.9%;p<0.05),且在接受DFO治疗的患者中情况更糟。根据我们的数据,我们认为TBI对胰腺功能有害,并推测DFO可能导致了这些患者中观察到的快速胰腺铁过载。