IMMUNOTHERAPY AFTER AUTOLOGOUS MARROW TRANSPLANTION
Project Number5R01CA058576-02
Contact PI/Project LeaderFEFER, ALEXANDER
Awardee OrganizationUNIVERSITY OF WASHINGTON
Description
Abstract Text
The success of autologous marrow transplantation (AMT) for the treatment
of patients with leukemia or lymphoma is limited largely by the high
incidence of recurrence of the malignancy after AMT. Immunotherapy in
the form of recombinant human IL-2 used alone or with ex vivo-generated
lymphokine activated killer (LAK) cells has induced regression of
advanced cancer in some patients and remissions in some patients with
acute leukemia or malignant lymphoma. IL-2/LAK therapy could potentially
represent a treatment modality which would not be cross-resistant with
the chemoradiotherapy used as a preparative regimen for AMT. Our goal
is to test the hypothesis that this approach, used early after AMT in a
setting of minimal residual disease, i.e., as consolidative
immunotherapy, may decrease the relapse rates. We have already (a)
demonstrated that IL-2-responsive LAK precursor cells are detectable in
the circulation early after AMT; (b) identified an IL-2 regimen which is
tolerable and induces immunomodulatory effects when administered early
after AMT; and (c) completed a feasibility trial of the IL-2 regimen plus
ex vivo-generated autologous LAK cells in patients who have undergone AMT
for advanced hematologic malignancy -- with encouraging preliminary
clinical results. The specific aim of this proposal is to perform a
randomized controlled trial of consolidative immunotherapy with IL-2 +
LAK cells vs. no IL-2/LAK after AMT in patients with non-Hodgkin lymphoma
and acute lymphoblastic leukemia so as to determine the effect, if any,
on their high relapse rates.
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