Allogeneic Hematopoietic Stem Cell Transplantation Using Intensified Conditioning Regimen and High dose Stem Cells in Severe Aplastic Anemia

Park, Chi Young; Min, Woo Sung; Shin, Ho Jin; Kim, Yoo Jin; Park, Yoon Hee; Kim, Hee Je; Lee, Seok; Min, Chang Ki; Kim, Dong Wook; Lee, Jong Wook; Park, Jong Won; Kim, Chun Choo

Abstract

BACKGROUND: Graft rejection as well as graft versus host disease is the main cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT) in patient with severe aplastic anemia. Graft rejection is associated with multiple transfusions before transplant. We added procarbazine (PCB) to the cyclophosphamide (CY) and antithymocyte globulin (ATG) conditioning regimen to overcome rejection since a synergistic immunuosuppressive effect between alkylating agents and ATG had been reported. In heavily transfused patients, G-CSF primed bone marrow+T cell depleted peripheral blood stem cell was used as the source of stem cells. Here we report the outcome in severe aplastic anemia patients receiving the intensified pretransplant conditioning and high dose stem cells to overcome graft rejection in these high risk patients.
METHODS
Between January 1995 and December 2000, among 113 patients with severe aplastic anemia who underwent allogeneic- HSCT after conditioning with CY+ATG+PCB, 90 patients were enrolled and divided into three groups. Thirty eight patients who received a small amout of transfusion were transplanted with bone marrow stem cells alone (group 1). In heavily transfused patients, 32 patients transplanted with bone marrow stem cells alone (group 2), and 20 patients transplanted with high dose stem cells (group 3). We evaluated the effect and outcome of a high dose stem cell transplantation, retrospectively.
RESULTS
The median age of all patients was 29 years (range 16 to 50) and median follow up duration was 30 months (range 1 to 80). Male to female ratio was 61 : 52. Six-year estimated overall survival of all patients was 88.4%. Sixteen patients (14.1%) experienced in graft rejection. A significant statistical significancy was observed with result that the lowest rejection incidence (5%) was seen in group 3, compared with 28.2% in group 2 (P= 0.02) and 13.1% in group 1. The incidence of acute and chronic graft versus host disease among patients with sustained engraftment was respectively 9.4%, 15.6% in group 2, and 20%, 20% in group 3 (P=0.4, P=0.78). Six- year estimated overall survival was 78% in group 2, and 90% in group 3 (P=0.24).
CONCLUSION
These results suggest that allogeneic-HSCT with high dose stem cells is an effective treatment to overcome graft rejection in heavily transfused severe aplastic anemia patients