Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection.
Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate. The number of prior transfusions was 0-276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received </=15 and >15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for </=50 and >50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.
University of São Paulo, Brazil.
F L
FL
Dulley
A C
AC
Vigorito
F J P
FJ
Aranha
D
D
Sturaro
M A
MA
Ruiz
R
R
Saboya
M C M A
MC
Macedo
R L
RL
Da Silva
D A F
DA
Chamone
J
J
Mehta
A
A
Bacigalupo
C A
CA
De Souza
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous
D003520:Cyclophosphamide; D002066:Busulfan