Reduced-intensity Conditioning Allogeneic Hematopoietic Cell Transplantation Followed by Prophylactic Dose-escalating Donor Lymphocyte Infusions in Higher Risk Myelodysplastic Syndrome
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Myelodysplastic Syndrome
- Sponsor
- Cooperative Study Group A for Hematology
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- relapse incidence,duration of remission
- Last Updated
- 15 years ago
Overview
Brief Summary
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
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
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
relapse incidence,duration of remission
Time Frame: 4years
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.
Secondary Outcomes
- engraftment, donor chimerism, secondary graft failure,GVHD(4 years)