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Donor Lymphocytes May Reverse Relapsed Leukemia

Donor Lymphocytes May Reverse Relapsed Leukemia

CHICAGO--Donor lymphocyte infusion is proving to be a potent treatment
for chronic myelogenous leukemia (CML) patients who relapse after
allogeneic bone marrow transplant (BMT). It also may improve the
overall outcome of CML patients after transplantation, said William
Drobyski, MD, at the sixth annual Malnati Symposium in the Clinical
Sciences, sponsored by Northwestern University School of Medicine.

"Donor lymphocyte infusion is a powerful form of adoptive
immunotherapy that is able to eradicate multiple logs of leukemia
cells," said Dr. Drobyski, associate professor of medicine,
Medical College of Wisconsin, Milwaukee. However, the treatment
has been most effective in patients with CML. "Response in
these patients has been durable and may be potentially curable,"
he added.

Chronic myelogenous leukemia patients who are treated early in
the course of their disease, ie, when they are in cytogenic relapse
or in the stable chronic phase, respond much more readily to donor
lymphocyte infusion than do individuals with more advanced phases
of CML.

The response also appears to be evolutionary, taking time to develop,
Dr. Drobyski said. "In our experience at the Medical College
of Wisconsin, the median time to cytogenic remission for CML patients
treated with donor lymphocyte infusion typically is 4 months;
the time to molecular remission is 8 months."

Because remission takes time to evolve and an aggressive disease
state fails to respond to this form of treatment, "it appears
that the clinical efficacy of donor lymphocyte infusion requires
that the tumor cell population not be growing so rapidly that
it overwhelms any antileukemia response of the transplant,"
he said.

The question for Dr. Drobyski, nevertheless, is not whether donor
lymphocyte infusion can salvage a few patients who have relapsed.
It is whether the procedure may improve the overall outcome of
patients undergoing BMT for CML, thus prolonging remission and
potentially eradicating the disease.

Dr. Drobyski began testing this hypothesis by combining donor
lymphocyte infusion with a T-cell depleted BMT graft. A total
of 21 patients with CML in primary phase received human leukocyte
antigen (HLA) identical bone marrow grafts at the Medical College
of Wisconsin between 1988 and 1996.


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