Autologous Bone Marrow Transplantation - Blog Science Connections

Conditioning Regimens in AML 101
Leukemia was induced in a female brown Norway rat by 9,10-dimethyl-l,2-
benzanthracene. The disease shows a reproducible growth pattern upon
intravenous cellular transfer within the brown Norway rat strain, and it is
cytologically and cytochemically similar to human acute promyelocytic
leukemia. Further analogies with the human disease are: 1 ) slow growth rate
(10 7 BNML cell kill after 18-23 days; growth fraction, 0.60-0.40); 2) severe
suppression of normal hematopoiesis because of an absolute numerical
decrease in the number of normal hematopoietic stem cells; 3) diffuse
intravascular coagulation; 4) prolonged blood transit time of leukemic cells
(34-36 hours); 5) response to chemotherapy as in human AML; 6) presence of
clonogenic leukemic cells (including in vitro colony formation; TDso, 25 cells);
7) low antigenicity; and 8) no evidence for a virus as an etiologic agent.
Cytostatic Agents
Cyclophosphamide was kindly provided by Asta-Werke, Bielefeld, Federal
Republic of Germany. The drug was dissolved in 0.9% saline and injected
intraperitoneally. Busulphan was a gift from the Wellcome Company,
Beckenham, England. It was dissolved in carboxymethylcellulose and injected
intraperitoneally. Cytosine arabinoside (cytarabine), provided by The Upjohn
Co., Kalamazoo, Ml, USA, was dissolved in 0.9% saline and injected intravenously
into the tail vein.
Total Body Irradiation
The procedure for TBI has been described extensively (4). In short, TBI was
carried out with a 7-radiation source (Gammacel 220, 137 Cs, Atomic Energy of
Canada, Ltd.) yielding a dose rate of 1.15 Gy/minute. The D 0
for 7-rays in vivo
for BNML cells is 0.85 Gy, with an extrapolation number of 3.7.
Determination of Log Leukemic Cell Kill by Different Conditioning
Regimens
Given the linear dose-effect relationship between the number of (injected)
leukemic cells and the survival time (2), the log leukemic cell kill induced by any
given treatment regimen is deduced from the increase in life span as compared
with that of nontreated leukemic control rats, according to the rule that a 4-day
prolongation of life span corresponds to a 1 -log cell kill. All experiments were
started on day 13 after inoculation with 10 7
BNML cells (i.e., at a total body
tumor burden of approximately 5 x 10 9 -10 10
cells).
RESULTS AND DISCUSSION
Cyclophosphamide and Total Body Irradiation
At a dose of 100 mg of CY/kg, a 5-log leukemic cell kill was induced, the
LDso for CY being 164 mg/kg (5). Higher dosages, in combination with