Related Experiment Videos
BMT for severe aplastic anemia using cyclosporine
W S May1, L L Sensenbrenner, W H Burns
1Bone Marrow Transplant Service, Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Insights
Hematopoietic stem cell transplantation (HSCT) using HLA-identical sibling bone marrow (BM) offers high survival for severe aplastic anemia (SAA). Further research is needed to address graft instability post-transplant.
Area of Science:
- Hematology
- Immunology
- Transplantation Medicine
Background:
- Severe aplastic anemia (SAA) is a life-threatening condition.
- Hematopoietic stem cell transplantation (HSCT) is a potential curative therapy.
- Previous HSCT protocols had variable outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of HSCT for SAA.
- To assess long-term survival and complications.
- To identify areas for improvement in HSCT protocols.
Main Methods:
- Retrospective analysis of 24 SAA patients undergoing HSCT.
- HLA-identical sibling donor bone marrow (BM) transplantation.
- Conditioning with cyclophosphamide (CY) and post-transplant immunosuppression with cyclosporine (CYA).
Main Results:
- Overall long-term survival was 79%.
- Graft failure occurred in 2 patients (primary engraftment failure) and 5 patients (secondary graft instability).
- Low incidence of acute and no chronic graft-versus-host disease (GVHD).
Conclusions:
- HSCT with CY conditioning and CYA immunosuppression is well-tolerated with excellent survival for SAA.
- High rates of graft instability warrant further investigation into post-transplant immunomodulation strategies.
Abstract:
Between 1984 and 1991 24 patients with severe aplastic anemia (SAA) were transplanted with HLA identical sibling donor BM. The overall long-term survival was 79 +/- 8%. The average age was 21 years (range 4-53 years) and the median pre-transplant disease duration was 35 days (range 12-2998 days). Over one-half (15 of 24) of the patients had received > 10 units of blood product transfusions prior to BMT. The pre-transplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY). Cyclosporine (CYA) was administered from 2 days prior to BMT and continued for 6-12 months. Two of the 24 patients failed to achieve primary engraftment (FTE). One of these patients had autologous recovery of BM function and is alive and well. Five of the 22 patients who engrafted failed to sustain engraftment (FTSE). Of these, three are alive and well following a second BMT or marrow boost. Only 1 of the 22 patients who engrafted had clinically significant (i.e. Stage II-IV) acute GVHD. No patient developed chronic GVHD. Our results indicate that BMT following a regimen consisting of CY with the continuous use of CYA in the post-transplant period is well tolerated and associated with excellent long-term survival. The high incidence of secondary graft instability (i.e. FTSE), however, suggests that future studies should focus on post-transplantation immunomodulation.