Iron Overload in Patients Undergoing Donor Stem Cell Transplant

Study Overview
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Brief Summary
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RATIONALE: Learning about the effect of excess iron in the liver of patients undergoing donor stem cell transplant may help doctors plan treatment. PURPOSE: This study is investigating the effects of iron overload in patients undergoing donor stem cell transplant.

Detailed Description
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OBJECTIVES: Primary Determine the impact of pre-transplant iron overload (defined as liver iron concentration [LIC] above normal [> 1.8 mg/g] on an MRI of the liver measuring tissue proton transverse relaxation rates [R2 MRI]) on the probability of 1-year overall survival of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Secondary Determine the impact of pre-transplant iron overload on the composite endpoint of non-relapse mortality and complications (e.g., serious infections, hepatic veno-occlusive disease, or organ failure) within 1 year after allogeneic HSCT. Determine the impact of pre-transplant iron overload on the 1-year cumulative incidence of acute or chronic graft-vs-host disease in patients with acute leukemia or myelodysplastic syndromes undergoing allogeneic HSCT. Determine the impact of pre-transplant iron overload on the 1-year probability of overall survival and non-relapse mortality in patients undergoing allogeneic HSCT. Determine the prevalence of pre-transplant iron overload in adult patients undergoing allogeneic HSCT. Determine the correlation between pre-transplant ferritin levels and LIC on R2 MRI. Compare the longitudinal measures of serum ferritin levels after allogeneic HSCT in patients with iron overload vs those without iron overload. Estimate the cumulative incidence of iron overload at 1 year after allogeneic HSCT. OUTLINE: Patients undergo blood sample collection to measure serum ferritin levels at baseline (pre-transplant) and then at 3, 6, 9, and 12 months after transplant. Patients with serum ferritin > 500 ng/mL also undergo an R2 MRI at baseline (pre-transplant) and at 12 months after transplant to determine liver iron concentration. Patients with serum ferritin > 500 ng/mL at 12 months after transplant also undergo an R2 MRI.

Official Title
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Iron Overload in Allogeneic Hematopoietic Cell Transplantation

Conditions
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Cancer, Hematopoietic Stem Cell Transplantation, Allogeneic Hematopoietic Cell Transplantation

Intervention / Treatment
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* Procedure: magnetic resonance imaging
* Procedure: Serum ferritin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Planning to undergo allogeneic hematopoietic stem cell transplantation using either myeloablative or reduced-intensity conditioning Any diagnosis allowed Not pregnant Weight ≤ 350 lbs Must be able to give written informed consent indicating the investigational nature of the study and its potential risks. Exclusion Criteria: Claustrophobia Other contraindication for MRI (e.g., cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, insulin or infusion pump, or implanted drug infusion device)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Without Iron Overload<br>Patients entering study without pre-HSCT iron-overload. Iron overload will be defined as liver ion concentration (LIC above normal (>1.8 mg/g) on R2 magnetic resonance imaging (MRI) of the liver. | Procedure: magnetic resonance imaging<br>* MRI of the liver will be performed within 30 days prior to HSCT (day 0) and can be done during receipt of conditioning regimen chemotherapy and/or radiation therapy. MRI will also be performed in selected patients at 1 year post-HSCT. This MRI will be done within ± 30 days of their 1-year post-transplant followup date. The R2 MRI is a specific MRI technique and cannot be used for the purpose of general diagnostic imaging. In our study, this modality is being used specifically for the estimation of LIC.<br>* Other names: R2 MRI;Procedure: Serum ferritin<br>* Blood samples will be taken pre-transplant, 3, 6, 9 and 12 months post-transplant<br>|
| With Iron-Overload<br>Patients entering study with pre-HSCT iron-overload. Iron overload will be defined as liver ion concentration (LIC above normal (>1.8 mg/g) on R2 magnetic resonance imaging (MRI) of the liver. | Procedure: magnetic resonance imaging<br>* MRI of the liver will be performed within 30 days prior to HSCT (day 0) and can be done during receipt of conditioning regimen chemotherapy and/or radiation therapy. MRI will also be performed in selected patients at 1 year post-HSCT. This MRI will be done within ± 30 days of their 1-year post-transplant followup date. The R2 MRI is a specific MRI technique and cannot be used for the purpose of general diagnostic imaging. In our study, this modality is being used specifically for the estimation of LIC.<br>* Other names: R2 MRI;Procedure: Serum ferritin<br>* Blood samples will be taken pre-transplant, 3, 6, 9 and 12 months post-transplant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Number of patients alive at 1 year. | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of non-relapse mortality | Number of patients who died due to serious infections, hepatic venous occlusive disorder (VOD) or organ failure within one year of transplant. | Up to 1 Year | 
| Acute and chronic graft-vs-host disease | Number of patients who had acute and chronic graft versus host disease through 1 year after transplant. | 1 Year Post Transplant | 
| Overall survival and non-relapse mortality | Number of patients who were alive and did not have any non-relapse mortality events at 1 year post transplant. Determine the impact of pre-transplant iron-overload on 1-year probability of overall survival and of non-relapse mortality in allogeneic HSCT recipients with acute leukemia and myelodysplastic syndrome. | 1 Year Post Transplant | 
| Number of Patients with Iron Overload | Prevalence of iron overload in patients being considered for allogeneic HSCT | Baseline | 
| Ferritin levels and Liver Iron Concentration | Correlation between pre-transplant and post-transplant ferritin levels and liver iron concentration on an MRI of the liver measuring tissue proton transverse relaxation rates (R2 MRI) | Baseline, and 3, 6, 9, and 12 Months Post Transplant | 
| Longitudinal averages of serum ferritin levels | Compare the longitudinal measures of serum ferritin between the no iron-overload and iron-overload groups. | Post Transplant | 
| Incidence of iron overload | Compare the longitudinal measures of serum ferritin between the no iron-overload and iron-overload groups. | 1 Year Post Transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron overload