Total body irradiation and iron chelation treatment are associated with pancreatic injury following pediatric hematopoietic stem cell transplantation

Abstract

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.

Hospitalization Outcomes of Acute Pancreatitis in Hematopoietic Stem Cell Transplant Recipients

“…The application of myeloablative or reduced-intensity chemotherapy regimens and total body irradiation prior to HSCT puts patients at risk for the development of acinar cell injury, leading to AP [ 5 ]. Iron overload from cytotoxic chemotherapy and pre-HSCT blood transfusions can further damage the pancreas [ 10 ]. Immunosuppressive medications such as thalidomide, calcineurin inhibitors, and steroids are frequently used in HSCT recipients and are common causes of AP [ 11 ].…”

Benefits and Risks in Polypathology and Polypharmacotherapy Challenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease

“…In particular, the prospect of chelating drug toxicity increases in TM patients with low or normal iron stores [91]. Within this context, the use of DFRA is not recommended for iron loaded patients with serum ferritin lower than 500 µg/L [92][93][94][95][96]. Some toxic side effects have also been reported in iron loaded TM patients treated with DFRA, which however are less frequent than in non-iron loaded categories.…”

Evaluation of Pharmacokinetics and Pharmacodynamics of Deferasirox in Pediatric Patients

“…In patients affected by hematological malignancies or who underwent a hematopoietic stem cell transplantation (HSCT), IO is considered multifactorial [ 2 ]. Intensive cytotoxic therapy before HSCT causes bone marrow and neoplastic cell lysis, releasing free and protein-bound iron and inducing excessive iron storage [ 3 ]. IO has been associated with poor prognosis in patients undergoing allogeneic HSCT, correlating with an increased risk of non-relapse mortality and acute and chronic graft-versus-host disease (GVHD) [ 4 , 5 , 6 ].…”