Adoptive Immunotherapy in Chimeras with Donor Lymphocytes

Allogeneic stem cell transplantation has a well-defined indication
in the treatment of hematological malignancies. The beneficial
immune effect of allogeneic marrow transplantation has long been
known, but only recently have methods been developed to separate
the graft-versus-leukemia (GVL) effect from graft-versus-host
disease (GVHD). Animal experiments have shown that lymphocytes from
the marrow donor can be transfused without causing severe GVHD if
stable chimerism and tolerance is established. First clinical
studies have been preformed in patients with recurrent chronic
myelogenous leukemia. In these patients complete molecular
remissions were induced that persist without further maintenance
treatment. These results have been confirmed in larger multicenter
studies in Europe and the USA. The best results were obtained in
chronic myelogenous leukemia (CML); repeated successes have been
reported in relapsing acute myeloid leukemia (AML), myelodysplastic
syndromes and multiple myeloma (MMY), and rare responses were
reported for acute lymphoid leukemia. Contrary to animal
experiments GVHD has been observed in human patients although to a
lesser extent than expected in transplants not given
immunosuppression. Secondly myelosuppression has been observed in
patients treated with relapsing CML. In CML the incidence of GVHD
could be reduced by depleting CD8(+) T cells from the donor
lymphocyte concentrate. Alternatively only small numbers of T
lymphocytes can be transfused and in the case of failing responses,
the numbers of donor lymphocytes may be increased. Results in
recurrent AML have been improved by the use of low-dose cytosine
arabinoside, granulocyte-macrophage colony-stimulating factor and
granulocyte colony-stimulating factor mobilized blood cells as
compared to lymphocytes only. In MMY the response rate is higher
than in AML, but the remissions are of limited duration in most
patients. Several protocols have been designed to include
preemptive donor lymphocyte transfusion in patients with a high
relapse risk after transplantation. Problems remain to avoid
chronic GVHD and to circumvent the immune escape mechanisms of
leukemia. Copyright (C) 2003 S. Karger AG, Basel.