Autologous Bone Marrow Transplantation - Blog Science Connections

120 Recovery After 4-Hydroperoxycyclophosphamide
during these clinical trials many patients had delayed bone marrow recovery, we
carried out a study to determine if the number of granulocyte-macrophage
colony-forming units, or progenitor cells (CFCIs-GM), after 4-HC treatment
correlated with the kinetics of bone marrow recovery.
METHODS
All protocols for the high-dose preparative regimen and ex vivo marrow
treatment were reviewed and approved by the Protection of Human Subjects
Committee of Montefiore Hospital. Informed consent was obtained from all
patients and from the parents of children who were patients.
Thirteen patients were included in this study (Table 1). Patients with acute
lymphocytic leukemia (ALL) (median age, 15 years) were significantly younger
than patients with AML (median age, 25 years). All patients had at least one
documented hematologic relapse of leukemia. The disease status of the
patients at the time of bone marrow transplantation is shown in Table 1.
The procedures for collecting and processing marrow have been described
in detail previously (6). In brief, 8 * 10 8
nucleated marrow cells per kilogram of
body weight were collected according to the method of Thomas and Storb (8).
Approximately one third of the collected marrow was treated ex vivo with 4-HC
at a concentration of 60 UQ/ml, and two thirds was treated with a concentration
of 100 uq/ml (for ten patients) or 120 fig/ml (for three patients). The 4-HC was
produced at the Johns Hopkins Oncology Center in Baltimore. The marrow
treated with the lower dose of 4-HC was reserved for infusion if engraftment with
the more heavily treated marrow failed. The treated marrows were frozen in a
controlled-rate liquid nitrogen freezer and then transferred to the liquid phase of
liquid nitrogen in a freezer storage cabinet. The day of the infusion of the
autologous bone marrow was designated day 0.
The CFCIs-GM were measured by an agar gel technique (9), which was
modified in that cells were separated by Ficoll-Hypaque. Cells were mixed with
Table 1. Patient Characteristics
Characteristic ALL AML
Number 6 7
Age (yr)
Median 15 a 25 s
Range 13-41 10-52
Male : Female 1 : 1 6 : 1
Early relapse 2 3
Isolated CNS relapse 1 1
2 Complete remissions 3 1
>2 Complete remissions 0 2
Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia.
"Significant difference between median ages (P < .05).