Autologous Bone Marrow Transplantation - Blog Science Connections

Recovery After 4-Hydroperoxycyclophosphamide 121
McCoy's medium containing 15% fetal calf serum in 0.3% agar. Pretreatment
marrow samples were plated at 1 x 10 5 cells/ml. Because of the reduction in
CFcls-GM after incubation with 4-HC, treated cells were plated at 1 x 10 6
cells/ml. Human fibroblast-conditioned medium served as a standard source of
colony-stimulating factor (10). Cultures were incubated for 7 days at 37°C in a
humidified atmosphere of 7.5% C0 2
in air. Colonies of more than 25 cells were
counted with the aid of a dissecting microscope.
Patients with AML received busulfan (1 mg/kg of body weight/dose orally
every 6 hours for 16 doses) on days -9, -8, -7, and -6, followed by cyclophosphamide
(50 mg/kg/dose i.v.) on days -5, -4, -3, -2. The bone marrow
was infused on day 0. Patients with ALL or AML with evidence of CNS disease
received cyclophosphamide (50 mg/kg i.v.) on days -8, -7, -6, and -5 and total
body irradiation (3 Gy/day, with the lungs shielded after 9 Gy) on days -4, -3,
-2, and -1 with bone marrow rescue on day 0.
Patients were cared for in single rooms using simple isolation. Before
transplantation, a right atrial catheter was placed in each patient. All patients at
risk for recurrence of herpes simplex infection received prophylactic intravenous
acyclovir. Broad-spectrum antibiotics were given for fever during aplasia, and
amphotericin was added for persistent fever. Antibiotics and isolation were
discontinued when the neutrophil count exceeded 0.5 x 10 9 /1- All blood
products were exposed to 2.5 Gy before infusion.
RESULTS
Time to hematologic recovery is shown in Table 2. Patients with ALL had a
significantly more rapid recovery than did patients with AML in neutrophil (P =
.023) and leukocyte counts (P= .025) but not in reticulocyte count (P= .21). The
slower rate of recovery in AML is also reflected in the number of patients who
required the back-up marrow. Although the differences are not significant by
chi-square analysis (P= .07), the reserve marrow was required by three of seven
patients with AML but none with ALL.
There was a marked reduction in CFOs-GM after a 30-minute exposure of
marrow cells to 4-HC (Table 3). Approximately 1% of the CFCls-GM remained
after incubation with this agent.
The relationship between the number of CFOs-GM infused and hematologic
recovery was examined for both ALL and AML. The log of the number of
Table 2. Median Days to Recovery With Autologous Bone Marrow
Transplantation
Group 500 Neutrophils//^" 1,000 WBCs/ul 8 1% Reticulocytes
AML 42 (22-59) 33 (24-60) 49 (29-185)
ALL 19.5 (17-35) 19.5 (14-33) 29 (17-40)
"Significant difference between median values (P < .05,).