Autologous Bone Marrow Transplantation - Blog Science Connections

102 Conditioning Regimens in AML
Table 1. Summary: Efficacy of Ablative Conditioning Regimens Before
Bone Marrow Transplantation in Acute Myelocytic Leukemia
Regimen
Log Leukemic
Cell Kill in Rat (BNML)
CY + TBI 8-9 25
TBI + CY 9 - 10= 10
CY+ Bu 10
% Relapse After
Allogeneic BMT in
First-Remission AML
HDAC + CY + TBI >10« 5-10
Bu + CY >10 0
Abbreviations: CY, cyclophosphamide; TBI, total body irradiation; Bu, busulphan;
HDAC, high-dose cytosine arabinoside.
a
20% treatment-related mortality.
» 25% treatment-related mortality.
isologous bone marrow transplantation, resulted in an increasing percentage of
toxicity-induced animal deaths and were thus abolished.
Although TBI alone appeared to be most effective if given as a single dose
(9.0 Gy: 4-log cell kill) compared with fractionated regimens (e.g., 2.25 Gy
daily x 4; 2.0 Gy twice daily * 4; 3.0 Gy twice daily x 2; 4.5 Gy daily x 3; 2- to
3-log cell kill; [4]), a combination of 100 mg/kg CY with either one 9.0-Gy TBI
fraction or fractionated TBI (2.0 Gy twice daily x 3.5, or 4.5 Gy TBI daily x 3)
resulted in a 9-log leukemic cell kill. With the reverse order—i.e., 9.0-Gy TBI
followed by 100 mg/kg CY—a 9- to 10-log leukemic cell kill was achieved at the
expense of 20% treatment-related mortality. At present, the underlying
mechanism of the increased efficacy and toxicity of TB1/CY compared with
CY/TBI is unknown.
If, preceding CY/TBI treatment ( 100 mg/kg CY; 9.0-Gy TBI), the total body
tumor load was reduced by cytarabine in a regimen of 200 mg/kg every 12
hours x 6, 75% cures were achieved (i.e., more than 10-log leukemic cell kill).
However, 25% toxic deaths were observed after this intense treatment
regimen (6).
Busulphan and Cyclophosphamide
Busulphan alone in a dose of 30 mg/kg (LD 50
,56 mg/kg) induced a 6-log
cell kill and was thus more effective than CY alone, given comparable normal
tissue toxicity. Cyclophosphamide (100 mg/kg) followed by Bu (30 mg/kg)
yielded a 10-log cell kill with 100% late relapses. The reverse order—similar
dosages of Bu followed by CY—resulted in 25% cures (more than 10-log
leukemic cell kill) and 75% relapse deaths.
In summary, as indicated in Table 1, the efficacies of the various