VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

Otherwise toxicity was mild to moderate and dominated by musculoskeletal
discomfort, fatigue, fever, skin rashes and nausea.
An increase in NK cell (CD 16+, and CD 56 + CD3-) numbers was observed
during the treatment periods with lower numbers recorded before and after the
treatment (Figure 1 and 2). NK cell activity measured as killing of K562 cells as
well as LAK cell activity measured as killing of Daudi cells were increased in
individual patients (Figure 3). In individual cycles increases in monocyte and T
cell numbers were also observed.
Increased production in individual treatment cycles of TNF alpha, IL-1 and
interferon gamma has been reported previously 27
. To these observations have
now been added the measurements of IL-6 in serum before, during and after
treatment. Figure 4 shows that increases of IL-6 could be demonstrated during
the treatment.
Comparative studies underway
The knowledge of the importance of the immune function for the risk of relapse
of AML together with the data on the immunomodulatory properties of
Linomide as well as the safety of this compound formed the rationale for two
different prospective randomized studies aiming to determine if Linomide can
reduce the risk of relapse of AML after ABMT. One study is active in ten European
countries and one is in the US, Canada and Australia. Both of the studies
include patients with AML in complete remission eligible for autologous bone
marrow transplantation, regardless of prior antileukemic therapy.
Taken together the two studies have recruited almost 200 patients who are
treated with Linomide 0.2 mg/kg twice weekly or placebo. Time to relapse, relapse
rate, overall survival will be recorded as well as safety and immune parameters.
Toxicity has so far been manageable and dominated by musculoskeletal
discomfort, nausea, vomiting, edema, skin rash and diarrhea. No efficacy
data is available since the studies are blinded.
Conclusion
The high rates of remission as well as of relapse in acute myeloid leukemia
indicate that the most important opportunities for improvement of the cure rate
of this disorder lies in successful prevention of relapse. The experiences from
allogeneic bone marrow transplantation indicate that the immune function is of
importance for the relapse rate in this disorder. A variety of agents including
Linomide modulate immune functions in such a way that clinical studies are
warranted, where the aim is to determine if the relapse rate of AML can be decreased
by use of such agents. Results from currently ongoing clinical studies
will have to be awaited before the role of immunomodulatory agents in acute
myeloid leukemia can be defined.
REFERENCES
1. Rowe JM et al. Clinical trials in adults with acute myelogenous leukemia: The ECOG
experience in Acute Myelogenous Leukemia: Progress and Controversies, ed RP
Gale. New York, Wiley-Liss, 1990.
2. Schiffer CA, Mayer RJ. Cancer and leukemia Group B studies in acute myeloid
leukemia. In Acute Myelogenous Leukemia. Progress and Controversies, ed RP
40 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPIANTATION