Study of the Outcome of Patients With Acute Myeloblastic Leukemia and Myelodysplastic Syndrome Receiving Iron Chelation Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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Iron chelation, mostly associated with multiple red blood cell transfusion, is relatively common in patients with hematological malignancies receiving allo-HSCT. This multicenter prospective observational study is designed to establish the impact of iron chelation on relapse after allo-HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome. The investigators will compare the results obtained in the prospective study to those observed in a historical retrospective cohort of paired patients who did not receive chelation. Given our clinical experience and literature results, the investigators will evaluate the Exjade chelator. Although not demonstrated, the presence of mutations of the HFE gene could play an indirect role on leukemogenesis by promoting overload. It is therefore important to evaluate the status in this patient population.

Official Title
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Multicenter Prospective Observational Study of the Outcome of Patients With Acute Myeloblastic Leukemia (AML) and Myelodysplastic Syndrome (MDS) Receiving Iron Chelation Therapy (Exjade) After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Conditions
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Myeloid Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: EXJADE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults older than 18 years old Patients with AML or MDS in complete remission receiving CSH transplantation from a related or unrelated donor and after myeloablative or non-myeloablative conditioning. Patients with iron overload defined by at least one ferritinemia> 1000 μg / L in the 6th month after CSH allograft Creatinine less than 1.5 x ULN; ALAT and ASAT <2 x ULN Patients giving their informed consent (prior to performing any study procedure) Exclusion Criteria: Hypersensitivity to the Exjade Association with another iron chelator Proteinuria> 1g / 24h Acute and chronic hepatitis (B and C viruses); HIV Extended corrected QT History of ocular toxicity related to iron chelation treatment Gastrointestinal Abnormal Absorption of Oral Medications Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: EXJADE|The patient having given his consent, will begin the Exjade at 10 mg / kg per day if the ferritin level reached 1000 ng / ml at 6 months after allograft, for a minimum duration of three months and up to 6 months. The iron parameters will be evaluated at 3, 6, 9, 12, 18 and 24 months after the beginning of the exjade treatment. The evaluation of the disease will be carried out according to the practices of the center. It is recommended to have a washout period of one week between stopping the ciclosporin and the beginning of treatment by exjade.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of iron chelation on relapse-free survival rate | Relapse-free survival will be defined as the number of days between the date of diagnosis and the date of death and / or relapse (or censored at the end of follow-up). | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of relapse-free survival after allograft of chelated patients to allografted patients not receiving chelation. | Matching variables will include disease type (AML or MDS), prognostic factors (cytogenetics, molecular biology, age), donor type / matching, and type of conditioning. | At 2-year | 
| Cumulative incidence of GVHD | Acute and chronic GVHD date and maximum grade using international classification | 3 months, 1 and 2 years | 
| Rate of infection | during the observation period | Through study completion, an average of 4 years | 
| Hematological toxicity during administration of Exjade | Hemoglobin level; Current average frequency of transfusions | Through study completion, an average of 4 years | 
| Non-hematological toxicity during administration of Exjade | Ferritinemia | Through study completion, an average of 4 years | 
| Non-hematological toxicity during administration of Exjade | Transferrin | Through study completion, an average of 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukaemia, Myelodysplastic syndrome, Iron Chelation Therapy (Exjade), allogeneic Hematopoietic Stem Cell transplantation (Allo-HSCT)