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Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1201-1208
Complete Remission of Accelerated Phase Chronic Myeloid Leukemia by
Treatment With Leukemia-Reactive Cytotoxic T Lymphocytes
J.H. Frederik Falkenburg,
Amon R. Wafelman,
Peter Joosten,
Willem
M. Smit,
Cornelis A.M. van Bergen,
Rian Bongaerts,
Ellie Lurvink,
Menno van der Hoorn,
Petra Kluck,
James E. Landegent,
Hanneke C. Kluin-Nelemans,
Willem E. Fibbe, and
Roel Willemze
From the Departments of Hematology and Pharmacy, Leiden University
Medical Center, Leiden, The Netherlands; and the Department of Internal
Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
Relapse of chronic myeloid leukemia (CML) in chronic phase after
allogeneic stem cell transplantation (SCT) can be successfully treated
by donor lymphocyte infusion (DLI). However, relapse of accelerated
phase CML, blast crisis, or acute leukemia after allogeneic SCT are
resistant to DLI in the majority of cases. In vitro-selected and
expanded leukemia-reactive T-cell lines may be more effective in
inducing an antileukemic response in vivo. To treat a patient with
accelerated phase CML after allogeneic SCT, leukemia-reactive cytotoxic
T-lymphocyte (CTL) lines were generated from her HLA-identical donor.
Using a modification of a limiting dilution assay, T cells were
isolated from the donor, selected based on their ability to inhibit the
in vitro growth of CML progenitor cells, and subsequently expanded in
vitro to generate CTL lines. Three CTL lines were generated that lysed
the leukemic cells from the patient and inhibited the growth of
leukemic progenitor cells. The CTL did not react with lymphocytes from
donor or recipient and did not affect donor hematopoietic progenitor
cells. The 3 leukemia-reactive CTL lines were infused at 5-week
intervals at a cumulative dose of 3.2 × 109 CTL. Shortly
after the third infusion, complete eradication of the leukemic cells
was observed, as shown by cytogenetic analysis, fluorescence in situ
hybridization, molecular analysis of BCR/ABL-mRNA, and
chimerism studies. These results show that in vitro cultured leukemia-reactive CTL lines selected on their ability to inhibit the
proliferation of leukemic progenitor cells in vitro can be successfully
applied to treat accelerated phase CML after allogeneic SCT.
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