Bone marrow transplantation in pediatric patients with severe aplastic anemia: cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor.
OBJECTIVE
Graft rejection remains a serious problem in patients transplanted for severe aplastic anemia. Although additional immunosuppression with irradiation may decrease graft failure, significant sequelae may ensue. We evaluated a nonirradiation containing conditioning regimen for children with severe aplastic anemia with matched sibling donors utilizing cyclophosphamide and anti-thymocyte globulin (ATG). To accelerate myeloid recovery, GM-CSF was used posttransplant.


METHODS
Twelve patients, with a median age of 3 years underwent BMT from HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditioning was cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globulin 30 mg/kg x 3 days. GM-CSF was administered at 10 micrograms/kg until a neutrophil count of 1,000 was achieved. Cyclosporine alone was used for graft-versus-host disease prophylaxis.


RESULTS
All patients achieved durable engraftment at follow-up of 5-51 + months, with the exception of the identical twin. Median time to neutrophil counts > 200/microliters, 500/microliters, and 1,000/microliters were 12, 13, and 15 days, respectively. Acute GVHD of less than or equal to grade II occurred in four patients; one patient had grade III. This has resolved in all but one.


CONCLUSIONS
The nonradiation conditioning regimen of cyclophosphamide/ATG appears to achieve durable engraftment in transfused children with matched sibling donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its contribution to allogeneic transplant required further study.
Bunin
N
N
Division of Oncology, Children's Hospital of Philadelphia, PA 19104, USA.
Leahey
A
A
Kamani
N
N
August
C
C
D000293:Adolescent; D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D014181:Transplantation Immunology; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide