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Blood, 15 July 2002, Vol. 100, No. 2, pp. 442-450
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Low-dose total body irradiation followed by allogeneic lymphocyte
infusion may induce remission in patients with refractory
hematologic malignancy
Karen K. Ballen,
Pamela S. Becker,
Robert V. B. Emmons,
Thomas J. Fitzgerald,
Chung C. Hsieh,
Qin Liu,
Christine Heyes,
Yeteive Clark,
William Levy,
Jean Francois Lambert,
Frank Chiafari,
Irma Szymanski,
Sarah Rososhansky,
Mark A. Popovsky,
F. Marc Stewart, and
Peter J. Quesenberry
From the Cancer Center and Departments of Medicine,
Radiation Oncology, and Pathology, University of Massachusetts Memorial
Health Care, Worcester; Baltimore Rh Typing Laboratory, Baltimore, MD;
and the American Red Cross Cord Blood Program, Dedham, MA.
Allogeneic stem cell transplantation is curative for certain
cancers, but the high doses of chemotherapy/radiotherapy lead to
toxicity. Here, we treat patients with refractory cancer with 100 cGy
total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with
a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood
cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after
transplantation. Seven patients with solid tumors received a sibling
transplant and 6 received a cord blood transplant; none achieved donor
chimerism, but 1 treated at the higher dose level of
1 × 108 CD3+ cells/kg had a transient nodal
response. Twelve patients with hematologic malignancies were treated; 1 received a cord blood transplant and 11 received sibling donor cells.
Nine of these 11 patients achieved donor chimerism, ranging from 5% to
100%. Four patients had sustained complete remission of their cancers, including one patient with transient 5% donor chimerism. The
development of chimerism correlated with hematologic malignancy
(P < .001), total previous myelotoxic chemotherapy
(P < .001), T-cell dose (P = .03), and
graft-versus-host disease (P = .01). Tumor response correlated with donor chimerism (P = .01). Engraftment
was achieved in patients with hematologic malignancies who had been
heavily pretreated, suggesting the degree of immunosuppression may be a
determinant of engraftment. Low-dose TBI and allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy.
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