Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia [see comments]

Autor: A Ferrant, W Arcese, JM Goldman, D Niederwieser, P Ljungman, B Hertenstein, L Verdonck, Hans-Jochem Kolb, A Schattenberg, N Jacobsen
Rok vydání: 1995
Předmět:
Zdroj: Blood. 86:2041-2050
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v86.5.2041.bloodjournal8652041
Popis: HE ROLE OF ALLOGENEIC lymphocytes in the eradication of leukemia is well established. In mice, transplantation of allogeneic bone marrow eliminated leukemia, and transplantation of marrow from syngeneic donors failed.’ Allogeneic marrow transplantation as a form of adoptive immunotherapy of leukemia was limited by the inevitable occurrence of graft-versus-host disease (GVHD).’ Patients with GVHD had fewer relapses than patients without GVHD, but only patients with mild degrees of GVHD had a survival ad~antage.~ T lymphocytes are most probably responsible for GVHD and the graft-versus-leukemia (GVL) effect; depletion of T lymphocytes decreased the incidence and seventy of GVHD, but increased the risk of relapse.“,’ However, a beneficial effect of adding T lymphocytes early after transplantation on high-risk leukemia could not be shown. Transfusion of donor lymphocytes early after transplantation increased the incidence and seventy of acute GVHD without improving the control of leukemia? A possible solution of the dilemma between the risk of GVHD and the benefit of a GVL effect was sought in delaying the transfusion of donor lymphocytes to a time when GVH tolerance was established. In canine chimeras, the delay of the transfusion for 2 months or longer after transplantation prevented acute GVHD without abrogating the beneficial effect on chimerism and the transfer of immunity.’ Indeed, the first patients treated with transfusion of donor lymphocytes showed only mild or no GVHD.8 In the meantime, we8 and others9-I5 have shown that remissions can be induced in patients with chronic myelogenous leukemia (CML) in relapse after marrow transplantation by the transfusion of lymphocytes from the marrow donor without chemo or radiotherapy. Occasional patients with acute myeloid leukemia (AML) have benefited from donor lymphocyte transfusions,*6 but in general, the response of different types of leukemia to the GVL effects of donor lymphocyte transfusions is not known. Here we review the results T in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty-two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD andlor myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML. 0 7995 by The American Society of Hematology. reported by 27 transplant centers in the European Group for Blood and Marrow Transplantation (EBMT) and evaluate the risks and benefits of donor lymphocyte transfusions in patients with recurrent CML in various stages, AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), and polycythemia vera (PCV).
Databáze: OpenAIRE
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