Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients
Study Details
Study Description
Brief Summary
Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia.The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
The distinction between acquired and inherited disease may present a clinical challenge, but more than 80% of cases are acquired.
Therapy for aplastic anemia may consist of supportive care only, immunosuppressive therapy, or hematopoietic cell transplantation. Severe and very severe aplastic anemia have a high mortality rate with supportive care alone .
The British Committee for Standards in Haematology recommends treating infection or uncontrolled bleeding before administering immunosuppressive therapy, including in patients scheduled for hematopoietic cell transplantation. The Pediatric Haemato-Oncology Italian Association recommends hematopoietic cell transplantation from a matched sibling donor for severe aplastic anemia, and if a matched donor is not available, options include immunosuppressive therapy or unrelated donor hematopoietic cell transplantation.
Human leukocyte antigen (HLA)-matched sibling-donor hematopoietic cell transplantation is the treatment of choice for a young patient with severe or very severe aplastic anemia , being generally accepted for patients younger than 40 years.
Recent years have seen increasing the use of hematopoietic cells other than bone marrow (BM). These alternative graft sources include peripheral blood progenitor cells and granulocyte colony stimulating factor (G-CSF) bone marrow (G-BM). Several groups have demonstrated that peripheral blood progenitor cell transplantation has faster neutrophil and platelet engraftment compared to BM in patients with hematologic malignancies ; however, most adult studies also report an increase in chronic GVHD (cGVHD) Some adult studies describe improved survival with peripheral blood progenitor cells in adult recipients although survival generally was no different in those with standard-risk disease .
Cyclophosphamide (Cy)/anti-thymocyte globulin (ATG) is considered the standard conditioning regimen for patients with severe aplastic anemia undergoing hematopoietic cell transplantation from a HLA matched sibling donor, The introduction of a fludarabine (F-araA) based reduced intensity conditioning regimen has extended the availability of hematopoietic cell transplantation to patients who are older, heavily transfused and having delayed treatment from the time of diagnosis with HLA matched related/unrelated donors.
The addition of F-araA to the conditioning regimen has been shown to provide additional immunosuppression for engraftment without increasing toxicity in patients undergoing hematopoietic cell transplantation .
Also, conditioning with F-araA and Cy is associated with improved long-term survival compared to a historical cohort receiving Cy/ATG regimen in patients with severe aplastic anemia undergoing hematopoietic cell transplantation .
Adequate post transplantation immunosuppression is important not only for the prevention of GVHD, but also to secure adequate suppression of the host immune system and prevention of graft rejection. The administration of CsA alone or with or without short-course methotrexate or steroid should be considered the standard post transplantation immunosuppression. In addition to possibility of use of other immunosuppressive agents, including the use of mycophenolate mofetil, particularly in patients with renal impairment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Non ATG regimen the first 50% of patients will receive Fludarabine + cyclophosphamide prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood |
Drug: Non ATG Conditioning regimen
50% of the patients will receive Fludarabine + cyclophosphamide (F-araA 120 mg/m2 total dose for 3 days (d-3,-2,-1) over 1 h infusion and cyclophosphamide 25 mg/kg/d (d-5 to d-2) for 4 days over 1-h infusion prior to hematopoietic cell transplantation , then post transplant cyclophosphamide dose 50 mg/kg on days +3 and +4
Drug: GVHD Prophylaxis
Cyclosporine A (CsA 3 mg/kg) start day +5
Procedure: Allogenic Stem Cell Transplantation
using peripheral blood stem cells
|
| Experimental: ATG regimen the other 50% will receive Cyclophosphamide + ATG prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood |
Drug: GVHD Prophylaxis
Cyclosporine A (CsA 3 mg/kg) start day +5
Procedure: Allogenic Stem Cell Transplantation
using peripheral blood stem cells
Drug: ATG conditioning regimen
the other 50% of the patients will receive Cyclophosphamide + ATG
|
Outcome Measures
Primary Outcome Measures
- Overall Survival rate [two years]
Secondary Outcome Measures
- GVHD occurrence (Acute or Chronic), engraftment and transplant related mortality [two years]
- Relapse rate [two years]
- Progression free survival [two years]
Eligibility Criteria
Criteria
Inclusion Criteria:
- All patients with severe and very severe aplastic anemia for stem cell therapy.
Exclusion Criteria:
1- Contraindication to stem cell transplantation. 2 - Patients associated co-morbidities.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- Couban S, Simpson DR, Barnett MJ, Bredeson C, Hubesch L, Howson-Jan K, Shore TB, Walker IR, Browett P, Messner HA, Panzarella T, Lipton JH; Canadian Bone Marrow Transplant Group. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood. 2002 Sep 1;100(5):1525-31.
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- Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. Erratum in: Br J Haematol. 2016 Nov;175(3):546.
- Socié G. Allogeneic BM transplantation for the treatment of aplastic anemia: current results and expanding donor possibilities. Hematology Am Soc Hematol Educ Program. 2013;2013:82-6. doi: 10.1182/asheducation-2013.1.82. Review.
- Watanabe T, Takaue Y, Kawano Y, Koike K, Kikuta A, Imaizumi M, Watanabe A, Eguchi H, Ohta S, Horikoshi Y, Iwai A, Makimoto A, Kuroda Y; Peripheral Blood Stem Cell Transplantation Study Group of Japan. HLA-identical sibling peripheral blood stem cell transplantation in children and adolescents. Biol Blood Marrow Transplant. 2002;8(1):26-31.
- Wu Y, Yu J, Zhang L, Luo Q, Xiao JW, Liu XM, Xian Y, Dai BT, Xu YH, Su YC. [Hematopoiesis support of mesenchymal stem cells in children with aplastic anemia]. Zhongguo Dang Dai Er Ke Za Zhi. 2008 Aug;10(4):455-9. Chinese.
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