Reduced-intensity Conditioning Allogeneic Hematopoietic Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the feasibility and efficacy of reduced-intensity conditioning allogeneic HCT followed by prophylactic dose-escalating DLIs in patients with higher risk MDS.

Detailed Description
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Conditioning therapy Busulfan 3.2 mg/kg/d on d-7 to -6 Fludarabine 30 mg/m2 on d-7 to -2 ATG 1.5-3.0 mg/kg/d on d-3 to -1 Methylpred 2 mg/kg/d on d-4 to -1 Mobilization and harvest Donor G-CSF 10 mcg/kg/d s.c. on d-3 to 0 Harvest of PBMCs on d 0 to +1 Infuse G-PBMCs on d 0 to d+1. Donor G-PBMC infusion GVHD prophylaxis Cyclosporine 1.5 mg/kg i.v. q 12 hrs beginning on d-1 and changed to oral dosing (with twice the i.v. dose) when oral intake is possible. Tapered beginning between d+30 and d+60. Methotrexate 15 mg/m2 i.v. on d+2, and 10 mg/m2 i.v. on d+4 and d+7 Prophylactic dose-escalating DLIs Begin at d+120 or at least 2 wks after IST discontinuation. No evidence of recurrence or GVHD CD3+ cell dose increment q 4 wks 4Three dose levels

Official Title
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Reduced-intensity Conditioning Allogeneic Hematopoietic Cell Transplantation Followed by Prophylactic Dose-escalating Donor Lymphocyte Infusions in Higher Risk Myelodysplastic Syndrome

Conditions
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Myelodysplastic Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with higher risk MDS including chronic myelomonocytic leukemia RAEB-1 or RAEB-2 IPSS Intermediate-2 or High risk category Chronic myelomonocytic leukemia Patients with appropriate hematopoietic cell donor HLA-matched sibling HLA-matched unrelated donor HLA-mismatched familial donor 3.16 years old or older Exclusion Criteria: • Presence of significant active infection Presence of uncontrolled bleeding Any coexisting major illness or organ failure Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible

Ages Eligible for Study
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Minimum Age: 16 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse incidence,duration of remission | The efficacy of the treatment will be measured in terms of relapse incidence and duration of remission (the primary endpoints). The hematopoietic cell donors in the study will include HLA-matched sibling, HLA-matched unrelated donors, and HLA-mismatched familial donors. | 4years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| engraftment, donor chimerism, secondary graft failure,GVHD | •This study will evaluate engraftment, donor chimerism, secondary graft failure, acute and chronic graft-versus-host disease (GVHD), immune recovery, infections, non-relapse mortality, progression-free survival (PFS), and OS. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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higher risk MDS