Salvage Immunotherapy Research Articles

T-cell depletion plus salvage immunotherapy with donor leukocyte infusions as a strategy to treat chronic-phase chronic myelogenous leukemia patients undergoing HLA-identical sibling marrow transplantation: W.R. Drobyski, M.J. Hessner, J.P. Klein, et al. Blood 94:434–441, 1999

T-cell depletion plus salvage immunotherapy with donor leukocyte infusions as a strategy to treat chronic-phase chronic myelogenous leukemia patients undergoing HLA-identical sibling marrow transplantation: W.R. Drobyski, M.J. Hessner, J.P. Klein, et al. Blood 94:434–441, 1999

Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL‐2) and alpha‐interferon (A‐IFN) for stage D3 prostate carcinoma failing second‐line hormonal treatment

Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL‐2) and alpha‐interferon (A‐IFN) for stage D3 prostate carcinoma failing second‐line hormonal treatment

Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL-2) and alpha-interferon (A-IFN) for stage D3 prostate carcinoma failing second-line hormonal treatment.

Immunotherapy with subcutaneous rIL-2 and alpha IFN was administered to stage D3 prostate cancer patients after failure of secondary treatment with oral estramustine phosphate. Of a total of 15 patients, 2 are in partial response, with estramustine maintained after 44+ and 36+ weeks, respectively. Response to estramustine was observed initially in 7 of 13 patients, with a median duration of 12 weeks (range 8-20). No response to estramustine was observed in the remaining 6 patients. After the failure of estramustine, 13 patients were treated with immunotherapy. After the first cycle, progression of disease no therapy was given to those patients. A reduction of PSA levels was observed during the first cycle in 2 patients (15.3%); levels subsequently increased during the second cycle of treatment. A partial response was observed in 4 patients (30.7%), with a reduction of PSA levels in 3. The duration of response was 28 and 32 weeks in 2 patients who survived after failure for 18 and 21 weeks, respectively. Two patients are still alive, with continued partial response at 62+ and 42+ weeks. Side effects were represented mainly by a flu-like syndrome, associated with fever and nausea in all patients. The serum concentration of IL-10 was measured in 8 patients under study and in 11 matched controls. Levels higher than mean + 2D of controls before, during, or after immunotherapy were correlated with treatment failure, whereas levels below 6 ng/ml were encountered among the patients who showed a clinical response and a reduction of PSA during treatment. Within the limitations of this pilot study, it appears difficult to distinguish between a spontaneously slowly progressing disease and a true response to therapy.

Treatment of moderate and severe acute GVHD after allogeneic bone marrow transplantation.

We analyzed the treatment of acute GVHD following allogeneic, related or unrelated donor bone marrow transplantation (BMT). Of 510 patients transplanted between January 1986 and July 1991, 272 (53.0%) developed acute GVHD. Patients (n = 240) received treatment with either corticosteroids (n = 209), antithymocyte globulin (ATG)/prednisone (n = 26), or an anti-T cell immunotoxin (n = 5). After 28 days, 33% (79/240) had achieved a response to primary therapy; 24% a complete response. Ninety-five patients received 1 or more courses of salvage immunotherapy and 26 (27%) responded. In multivariate analysis, a response to primary therapy was the single most important factor independently predicting a lower risk of subsequent chronic GVHD (P < .0001) and improved long-term survival (P = .01). The GVHD clinical stage score, which we previously described, had significant predictive value for response to therapy and freedom from chronic GVHD. The conventional clinical grade had no such predictive value. In multivariate analysis, transplantation from a mismatched or an unrelated donor was not of independent importance in predicting either acute GVHD treatment response or chronic GVHD. However, these alternative donor transplants led to poorer survival. This analysis identifies patient subsets having GVHD with a low likelihood of response to conventional immunosuppressive treatment and may be used to indicate those needing early application of more intensive therapy. More important, however, the overall low response rates observed suggest that more effective treatment for acute GVHD is still required to improve the results of transplantation therapy.

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

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.

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

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.