Autologous Bone Marrow Transplantation - Blog Science Connections

ABMT in Acute Nonlymphocytic Leukemia 65
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MONTHS AFTER BMT
+ DF SURV A SURV
Figure 1. Survival analysis of 40 patients undergoing autologous bone marrow transplantation
for acute nonlymphocytic leukemia in second remission (30 patients) or third
remission (10 patients). Overall survival (SURV) (triang les) and disease-free survival (DF
SURV) ("crosses,) are shown; each symbol represents a living patient.
incidence of transplant-related complications). Analysis of leukemia-free survival
after ABMT must thus encompass similar studies of recipients of syngeneic
marrow grafts.
Two problems must be addressed in ABMT for acute leukemia in second
or subsequent remission: eradication of residual leukemia in vivo and of
clonogenic tumor from the marrow suspension ex vivo. Attempts to remove
occult leukemic cells from autologous marrow suspensions by physical
methods such as density-gradient centrifugation have been unsuccessful (20).
Although results with ex vivo immunologic treatment of autologous marrow
with monoclonal antibodies in patients with acute lymphocytic leukemia is
encouraging (21,22), the lack of satisfactory monoclonal antibodies that react
with myeloid blast cells has limited the applicability of such techniques for ex
vivo immunologic purging in acute nonlymphocytic leukemia.
A transplantable murine lymphoma system demonstrated the differences
between the sensitivity to antitumor agents of normal and neoplastic cells (23),
suggesting that incubation of autologous marrow with selected pharmacological
agents might eradicate residual leukemic cells yet spare normal
hematopoietic stem cells. Phase I clinical studies with the alkylating agent 4-HC
have shown that the ex vivo incubation of autologous marrow with up to 100