Flu+CPM+rATG Conditioning Regimes for Unrelated Bone Marrow Transplantation (UBMT)(or Mobilized Peripheral Blood)in Severe Aplastic Anemia (SAA)

Study Overview
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Brief Summary
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Anti-thymocyte globulin (ATG) has been used in severe aplastic anemia as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine based conditioning regimens without total body irradiation have been reported to be promising for BMT/PBSCT from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in UBMT/UPBSCT.

Detailed Description
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GVHD prophylaxis recommendation tacrolimus (0.03 mg/kg/day i.v. by continuous infusion from day -2 and taper with an oral form until 1 year after BMT/PBSCT) methotrexate (15 mg/m2 i.v. on days 1 and 10 mg/m2 i.v. on days 3, 6, 11)

Official Title
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Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Bone Marrow (or Mobilized Peripheral Blood) Transplantation in Severe Aplastic Anemia

Conditions
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Anemia, Aplastic

Intervention / Treatment
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* Drug: cyclophosphamide, fludarabine , thymoglobulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion. Peripheral blood Neutrophils < 0.5 x 109/l Platelets < 20 x 109/l Corrected reticulocytes < 1% Bone marrow Severe hypocellularity (< 25%) Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells No prior hematopoietic stem cell transplantation. Age: no limits. Performance status: ECOG 0-2. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. Heart: a shortening fraction > 30%, ejection fraction > 45%. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2. Patients must lack any active viral infections or active fungal infection. Appropriate donor is available: Matched in 6/6 of A, B, DR loci. Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion Criteria: Pregnant or nursing women. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. Psychiatric disorder that would preclude compliance. Congenital aplastic anemia including Fanconi anemia. Manipulated bone marrow.

Ages Eligible for Study
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Maximum Age: 25 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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine<br> | Drug: cyclophosphamide, fludarabine , thymoglobulin<br>* cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 & -6) fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 & -2) thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 & -1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the engraftment potential, incidence and severity of acute graft versus host disease,toxicity of conditioning regimen for UBMT in SAA. |  | From Jan. 1. 2006 to Dec. 31. 2008. For 3 years. | 
| To evaluate overall and EFS follow-up of 1 year after UBMT/PBSCT. |  | From Jan. 1. 2006 to Dec. 31. 2008. For 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate chronic GVHD and immunologic recovery after UBMT/PBSCT. and the efficacy of UBMT/PBSCT before immuno-suppressive therapy with anti-thymocyte globulin in severe aplastic anemia and long term toxicity of non-TBI based conditioning |  | From Jan. 1. 2006 to Dec. 31. 2008. For 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, UBMT, Severe