Autologous Bone Marrow Transplantation - Blog Science Connections

122 Recovery After 4-Hydroperoxycyclophosphamide
Table 3. CFUs-GM Before and After 4-HC Treatment
CFUs-GM/kg x 10-"
Group Cells/kg * 10-« Before 4-HC After 4-HC
AML 3.8 ± 0.2 20.6 ± 5.5 0.29 (1.5%)
ALL 4.0 ± 0.3 25.0 ± 15.4 0.19 (0.8%)
Abbreviations: CFUs-GM, granulocyte-macrophage colony-forming units; 4-HC, 4-
hydroperoxycyclophosphamide; AML, acute myelogenous leukemia; ALL, acute lymphocytic
leukemia.
CFCls-GM infused was compared with the number of days to achieve a WBC
count of l,000//il, neutrophil count of 500/jul, and reticulocyte count of 1%
(uncorrected). In ALL there was no correlation (Pearson coefficient) for the
neutrophil count (r = .795) or reticulocyte count (r = .640). Likewise, no
relationship was found in AML between the CFCI-GM dose and WBC count (r =
-.574), neutrophil count (r = -.534), or reticulocyte count (r = .159).
DISCUSSION
Autologous bone marrow transplantation is a promising therapy for acute
leukemia (6,7,11), but its results may be improved if residual leukemic cells can
be purged from the marrow. In this study, 4-HC was used as a purging agent, but
we found hematologic reconstitution was slow in this group of patients. The
median time to achieve a neutrophil count of 500/u\ in patients with AML was
42 days. This compares with 29 days in another series in which 4-HC was used
to purge marrow of patients with AML (7). This delayed engraftment may be
attributed in part to damage of the progenitor cell by 4-HC. Approximately 1 % of
harvested CFCls-GM remain after treatment with 4-HC. Other investigators have
had similar experiences (12,13).
In our series, the marrow of patients with AML recovered much more slowly
than did the marrow of patients with ALL. This delay did not appear to result
from a difference in disease status, harvested number of CFCls-GM, or number
of CFCls-GM infused. These findings suggest that patients with AML may have
greater damage to their stem cell compartment from their disease or prior
therapy. It is possible that such stem cells may be more susceptible to injury
from exposure to 4-HC.
Our data also suggest that no relation exists between the number of
CFCls-GM infused and bone marrow recovery for patients with ALL or AML.
Clearly, the toxicity of 4-HC to CFGs-GM is not solely responsible for delayed
recovery because patients with ALL had fewer residual CFCls-GM yet they
showed more rapid engraftment. Perhaps 4-HC is acting on an earlier
progenitor cell than the CFCls-GM. Others' results indicate a reduction in certain
human pluripotent hematopoietic colony-forming cells (13) but only limited
effects on primitive blast cell colonies after exposure to 4-HC (14).