Graft-versus-leukemia reactions after bone marrow transplantation

Abstract

To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non--T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non-- T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non--T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01), and both acute and chronic GVDH (relative risk 0.33, P = .0001) as compared with recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001) than recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.

Allogeneic bone marrow transplantation with T‐cell‐depleted marrow grafts for patients with poor‐risk relapsed low‐grade non‐Hodgkin's lymphoma

“…We believe that the favourable results of allogeneic BMT cannot be explained merely on the basis of the intensive conditioning regimen before BMT, but also on immunological mechanisms after BMT (Meijerink et al, 1994). As already shown for acute leukaemia, chronic myeloid leukaemia and multiple myeloma, one of the additional beneficial effects of BMT, whether or not followed by DLI, is the immune-mediated graft-versus-tumour effect (Horowitz et al, 1990;Kolb et al, 1995;Collins et al, 1997;Lokhorst et al, 1997). Especially in patients with relapsed chronic myeloid leukaemia post-BMT, DLI induce renewed remission in the majority of patients, whereas patients with acute leukaemia respond less favourably to DLI.…”

Management of Relapsed Acute Myeloid Leukaemia

“…Moreover, the recent development of low-intensity preparative regimens is of great interest and may be the basis of an immunomodulatory approach to transplantation that is widely applicable. There is considerable evidence for GvL effect in AML: relapse of AML is less common in patients with GvHD, relapse rates are higher in syngeneic transplants, spontaneous remission has been observed following the onset of acute GvHD, there is a lower relapse risk after unrelated donor BMT, a higher relapse risk with combined post-transplant immune suppression with cyclosporine/methotrexate than with methotrexate alone, higher relapse with the more immune suppressive FK 506 than cyclosporin, and higher relapse in T-cell-depleted grafts (Higano et al, 1990;Horowitz et al, 1990;Gajewski et al, 1990;Sullivan et al, 1989;Weiden et al, 1981). Interleukin 2 (IL2) has well-recognized immunomodulatory properties and has been shown to produce responses in some patients with relapsed AML (Foa et al, 1991;Meloni et al, 1994Meloni et al, , 1996.…”

Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

“…The RIC regimen aims to take advantage of the graft-versus-leukemia (GvL) effect mediated by the donor's immunocompetent cells, rather than the upfront cytoreductive effect of the conditioning chemotherapy. 11 However, in refractory AML, RIC may not control the disease sufficiently to allow a GvL effect to occur. In an attempt to overcome this problem, the so-called "sequential" transplant approach was developed, which combines a short, intensive course of salvage chemotherapy to decrease the leukemia cell burden with RIC.…”