Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose

Abstract

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus- leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.

Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy

“…Approximately 70% of CML patients relapsing into chronic phase achieve complete remission after donor lymphocyte infusion (Cullis et al, 1992;Antin, 1993;Drobyski et al, 1993;Kolb et al, 1995;Bacigalupo et al, 1997;Collins et al, 1997;Raanani et al, 1997). Similar results have been achieved with HLA-identical sibling or matched unrelated donors .…”

“…The most striking and direct evidence supporting the concept of GVL is the observation that many patients who relapse after allogeneic transplantation can be reinduced into complete remission by infusing additional donor lymphocytes (Cullis et al, 1992;Antin, 1993;Drobyski et al, 1993;Van Rhee et al, 1994;Kolb et al, 1995;Mackinnon et al, 1995). After engraftment of an allogeneic transplant, immune reconstitution generally occurs exclusively from donor-derived immunocompetent cells.…”

Cellular therapy services provided by blood centers and hospitals in the United States, 1999: an analysis from the Nationwide Blood Collection and Utilization Survey

“…The fact that these two product categories are very distinct from each other is illustrated by the data on each. Allogeneic lymphocytes, which would include products commonly called donor lymphocyte infusions, are typically used to provide a graft‐versus‐leukemia effect in patients with relapsed leukemia or in conjunction with allogeneic nonmyeloablative hematopoietic transplantation to promote full donor engraftment 10,11 . We captured 428 lymphocyte infusion episodes for 308 recipients, 99 percent of which were allogeneic.…”

Cellular engineering for the production of blood components

“…As an adjunct to HPC transplantation, adoptive immunotherapy involves supplemental transfusions of donor lymphocytes. This induces remission and may prevent relapse of chronic myelogenous leukemia (CML) following HPC transplantation 25–27 . Routine apheresis techniques are used to obtain the lymphocytes, which are transfused without extensive manipulation.…”