Abstract on Reducing Morbidity from Allo Transplants

[Guest guest]

[We posted the press release on this article this past week. Here is

the abstract.

This is potentially important news because acute GvHD is one of the

main causes of allogeneic stem cell transplant mortality.]

Protective Conditioning for Acute Graft-versus-Host Disease

Lowsky, M.D., Tsuyoshi Takahashi, M.D., Ph.D., Yin Ping Liu,

M.D., Sussan Dejbakhsh-, M.S., F. Carl Grumet, M.D., Judith A.

Shizuru, M.D., Ph.D., Ginna G. Laport, M.D., E. Stockerl-

Goldstein, M.D., J. ston, M.D., T. Hoppe, M.D.,

A. Bloch, Ph.D., Karl G. Blume, M.D., S. Negrin, M.D.,

and Strober, M.D.

ABSTRACT

Background Conditioning with total lymphoid irradiation plus

antithymocyte serum protects mice against acute graft-versus-host

disease (GVHD) after hematopoietic-cell transplantation. We tested

this strategy in humans.

Methods Thirty-seven patients with lymphoid malignant diseases or

acute leukemia underwent an experimental conditioning regimen with 10

doses of total lymphoid irradiation (80 cGy each) plus antithymocyte

globulin, followed by an infusion of HLA-matched peripheral-blood

mononuclear cells from related or unrelated donors who received

granulocyte colony-stimulating factor.

Results Of the 37 transplant recipients, only 2 had acute GVHD after

hematopoietic-cell transplantation. Potent antitumor effects in

patients with lymphoid malignant diseases were shown by the change

from partial to complete remission. In the transplant recipients who

underwent conditioning with total lymphoid irradiation and

antithymocyte globulin, the fraction of donor CD4+ T cells that

produced interleukin-4 after in vitro stimulation increased by a

factor of five, and the proliferative response to alloantigens in

vitro was reduced, as compared with normal control subjects and

control subjects who underwent conditioning with a single dose of

total-body irradiation (200 cGy).

Conclusions A regimen of total lymphoid irradiation plus

antithymocyte globulin decreases the incidence of acute GVHD and

allows graft antitumor activity in patients with lymphoid malignant

diseases or acute leukemia treated with hematopoietic-cell

transplantation.