3522
Lymphocyte Transfusion Therapy for Cancer Patients
To the Editor:
Over 20 years ago, it was shown that lymphocytes from normal
persons have the ability to kill tumor cells in vitro. Natural killer
(NK) cells are thought to be the cause this rapid in vitro killing.
To determine whether similar recognition and killing of cancer cells
can take place in vivo, six patients with advanced cancer were trans-
fused with 1 U of fresh blood from young, normal donors. The
experiment used one-HLA-haplotype-related donors to prevent
rapid rejection of the transfused cells. HLA-identical donors were
excluded to avoid graft-versus-host reaction^.^
Patient no. 1 was a 38-year-old white man with malignant gas-
trinoma metastatic from the duodenum to the liver. He underwent
extensive therapy, including chemo-embolization and freezing of the
liver (cryosurgery), and had multiple chemotherapeutic trials with
intermittent success. After experiencing increasingly severe hepatic
dysfunction, he received a transfusion from his one-HLA-haplotype-
matched brother. Within I week, there was a significant decrease
in the tumor marker levels. CA 19.9 levels decreased from 323 to
184 in 7 days and to 116 in 57 days (Fig I).
Patient no. 2 was a 76-year-old white woman with ovarian carci-
noma, marked ascites, and increasing shortness of breath from dia-
phragmatic compression. After undergoing all the usual trials for
carcinoma of the ovary, she received a transfusion from her one-
CORRESPONDENCE
HLA-haplotype-matched son. As a result of this procedure, her CA
125 levels decreased within 6 days (Fig 1).
Patient no. 3 was a 87-year-old man with metastatic squamous
cell carcinoma of the cheek. He had experienced two recurrences
that required resection and radical neck dissection followed by radia-
tion. Once the radiated site regrew, blood was transfused from his
one-HLA-haplotype-matched 25-year-old granddaughter. The in
vitro NK activity of the donor cells was 34% at a 50:l effector to
K562 target ratio.4 The lesion, which initially measured 3 x 2 X I
cm, was reduced to 2 X 2 X 0.5 cm within 2 days. After 5 days,
the lesion was further reduced to a thin plaque measuring less than
I mm in thickness. NK killing of the patients lymphocytes increased
from 8% pretransfusion to 25% at 6 days posttransfusion.
Patient no. 4, a 54-year-old white woman, was diagnosed with
metastatic melanoma. Her donor was her one-HLA-haplotype-
matched 34-year-old son. After the transfusion, one subcutaneous
nodule decreased in size from 2.5 X 2.0 cm to 2.0 X 2.0 cm in 1
day and to 2.0 x 1.8 cm after 8 days.
Patient no. 5 was a 74-year-old man with malignant melanoma
and a subcutaneous nodule. His donor was his 49-year-old daughter
with a one-HLA-haplotype match. The patients subcutaneous nod-
ule decreased in size from 2.8 X 2.6 cm to 2.4 X 2.2 in 5 days and
2.5 x 2.0 in 12 days. Two days after transfusion, 2% of the lympho-
cytes were of donor HLA type, A9, by flow cytometry.
Patient no. 6 was a breast cancer patient with extensive liver
CORRESPONDENCE 3523

from a healthy donor may be a better alternative for cancer immuno-

therapy. In addition, as noted in patient no. 6, stimulation with alloge-
neic cells may generate activated NK cells in the patient.
The recent report regarding spontaneous regression of chronic
myelogenous leukemia (CML) in blast crisis after transfusion6 can
be explained by this mechanism. Lymphocytes from HLA-identical
sibling donors have successfully rescued patients who experienced
a recurrence of CML after bone marrow transplantation? This obser-
vation proves that allogeneic lymphocytes can kill leukemic cells in
vivo.
We conclude that allogeneic transfusions from normal donors can
0 5 10 15 20 0 5 10 15 20 have an immediate effect on tumors, probably as a result of the NK
killing mechanism. This approach has almost no side effects and

'i-
may be applicable to a wide range of tumors.
3 m p G Z -
3000
Peter D. Boasberg
Kenneth M. Tokita
St Johns Hospital
1300 Santa Monica, CA
200 Paul I. Terasaki
Xiuming Wang

loo f Patient 6
0 5 10 15 20 0 5 10 15 20
Days after Transfusion
Fig 1. CA 19.9 levels expressad as units were determined with
Abbott kit and CA 125 levels were determined with the Centocor kit.
metastasis. Her CEA and CA 15.3 values decreased dramatically in
the 2 weeks after transfusion (Fig 1). At the same time, her NK
activity increased from the pretransfusion value of 16% killing to
29% at 7 days and 51% at 12 days. At 12 days, no donor cells could
be detected in the circulation by flow cytometry.
The rapid decrease in tumor volume and tumor markers after these
transfusions is consistent with the cytotoxic activity of NK cells,
which can occur within 4 hours in vitro? However, the observed
decreases did not continue for longer than 2 weeks and fell short of
inducing long-term remission. Therefore, we are now examining the
use of multiple transfusions and larger doses of lymphocytes through
leukophoresis. None of these patients had evidence of graft-versus-
host disease or toxic effects from the transfusion.
This approach does not require a period of immunization for the
lymphocytes. Thus, unlike the strategy of activating cytotoxic T
lymphocytes with interleukin-2 and other lymphokines: treatment
with NK cells can be very direct. If the tumor can be killed within
a few days, autologous cells are not necessary. Moreover, using the
proposed approach, lymphocytes from young, normal donors can be
used. The development of the tumor itself indicates that the patient's
cells may be hyporesponsive. Therefore, infusion of active NK cells
UCLA Medical School
Los Angeles, CA
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