Risk Factors and Measures to Prevent Liver and Pancreas Complications in Pediatric Patients After HSCT

NCT04423237 | Completed

• 1 other identifier: 1105/2015
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Hematopoietic Stem Cell Transplantation (HSCT) is currently a standard procedure for a wide range of blood-oncological diseases and genetic disorders. Recent improvements in transplant technologies, infection prevention and graft-versus-host-disease (GVHD) management procedures have significantly reduced the transplant-related mortality (TRM). However, approximately 50% of pediatric patients may develop liver dysfunction before HSCT and 74% to 85.5% after HSCT, with a TRM related to liver dysfunction reaching 46%. The liver and pancreas complications still remain too high for the difficulties and diagnostic inefficiencies and, consequently, for the lack of targeted and safer therapies. The diagnostic problems can be summarized in 3 major points: a) the histological examination of liver and pancreas parenchyma cannot be routinely performed because of the organ anatomy and the relative risk of the bioptic procedures; b) the lack of specific biomarkers or advanced imaging techniques appropriate for the diagnosis of HSCT complications; c) the multifactorial causes of organ complications, as well as drug toxicities, GVHD, siderosis, ductopenia (considered as an index of hepatic GVHD), the accumulation of potentially toxic substances favored by siderosis and ductopenia. In more than 50% of HSCT patients, siderosis and/or ductopenia may represent common pathological conditions. Furthermore, international guidelines issued by onco-hematology and transplantation scientific societies recommend a chelating treatment with deferasirox in all hematological and oncological patients undergoing an intense transfusion regimen. However, in the presence of siderosis and marked ductopenia, patients receiving deferasirox may experience both severe renal and hematological toxicities and lack of effectiveness of the chelating treatment. Therefore, the principal aim of the present retrospective study will be the evaluation of the transplant-related mortality (TRM) in patients requiring a chelation treatment according to the Italian guidelines in pediatric patients

Conditions

Iron Overload

Keywords

iron overload; deferasirox; children; HSCT; toxicity; ductopenia

Outcome Measures

Primary Outcomes (1)

• Transplant-related mortality (TRM)

  TRM in SIO/SIO+D patients treated with deferasirox as per Italian guidelines

  0-24 months after transplant

Secondary Outcomes (5)

• Post-HSCT liver and pancreatic complications

  0-24 months after transplant

• Time to iron concentration normalization

  0-24 months after transplant

• Statistical analysis of risk factors for ductopenia

  0-24 months after transplant

• Minimum plasma concentrations of deferasirox

  0-24 months after transplant

• Correlation of minimum plasma concentrations of deferasirox with drug tolerability

  0-24 months after transplant

Study Arms (2)

Severe Iron Overload (SIO)

Children affected by Severe Iron Overload who received DEFERASIROX

Drug: Deferasirox

Severe Iron Overload + Ductopenia (SIO+D)

Children affected by Severe Iron Overload + Ductopenia who received DEFERASIROX

Drug: Deferasirox

Interventions

Deferasirox DRUG

DEFERASIROX administered as per clinical practice and according to technical note

Also known as: Exjade or Deferasirox Milan

Severe Iron Overload (SIO); Severe Iron Overload + Ductopenia (SIO+D)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric inpatients who a) underwent a HSCT at the Bone Marrow Transplant Center, IRCCS Burlo Garofalo, and b) had a ≥2-year follow-up after transplant. All procedures were performed according to clinical routine protocols

You may qualify if:

• one or more allogeneic HSCT
• any type of disease (blood-oncological or genetic), from any type of donor (sibling, MUD, haploidentical) and with any source of stem cells (spinal cord, peripheral blood stem cells, cord blood)
• diagnosis of moderate-to-severe siderosis (by nuclear magnetic resonance imaging, MRI) and who needed a chelation treatment with deferasirox
• one or more liver biopsies in the post-transplant period to perform histological examinations
• Complete results from lab analyses
• year follow-up after HSCT
• therapeutic drug monitoring (TDM) protocol for deferasirox plasma concentration as per clinical routine
• Sign of the informed consent by the parents or legal representatives

You may not qualify if:

• Lack of liver biopsies after transplantation, results from laboratory analyses or TDM or MRI
• Lack of informed consent

Sponsors & Collaborators

• University of Pisa: lead
• IRCCS Burlo Garofolo: collaborator
• University of Genova: collaborator

Study Sites (1)

IRCCS Burlo Garofolo

Trieste, 34137, Italy

Location

Related Publications (2)

• Maximova N, Zanon D, Pascolo L, Zennaro F, Gregori M, Grosso D, Sonzogni A. Metal accumulation in the renal cortex of a pediatric patient with sickle cell disease: a case report and review of the literature. J Pediatr Hematol Oncol. 2015 May;37(4):311-4. doi: 10.1097/MPH.0000000000000322.

  PMID: 25811747 BACKGROUND

• Galeotti L, Ceccherini F, Fucile C, Marini V, Di Paolo A, Maximova N, Mattioli F. Evaluation of Pharmacokinetics and Pharmacodynamics of Deferasirox in Pediatric Patients. Pharmaceutics. 2021 Aug 11;13(8):1238. doi: 10.3390/pharmaceutics13081238.

  PMID: 34452199 RESULT

MeSH Terms

Conditions

Iron Overload

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Natalia Maximova, MD

  Institute for Maternal and Child Health, IRCCS Burlo Garofalo, Trieste, Italy

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor

Study Record Dates

• First Submitted: May 30, 2020
• First Posted: June 9, 2020
• Study Start: September 30, 2020
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: June 3, 2025

Record last verified: 2025-06

Locations

IT (1)