https://repository.ubn.ru.nl/bitstream/handle/2066/22128/22128___.PDF

Graft-Versus-Leukemia Effect of Donor Lymphocyte Transfusions in Marrow Grafted Patients

Over the past twenty years, clinical and laboratory studies have led to important new insights into the biology of chronic myeloid leukemia. Basic science has defined the molecular pathogenesis of chronic myeloid leukemia (CML) as unregulated signal transduction by the Bcr-Abl tyrosine kinase. Clinical studies have demonstrated that CML can be curable through immune-mediated elimination of leukemia cells by allogeneic T lymphocytes. Recently, specific inhibition of signal transduction by the tyrosine kinase Bcr-Abl has been found to be active in managing the disease.

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Chronic myeloid leukemia.

PURPOSERecipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality.PATIENTS AND METHODSWe surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis.RESULTSComplete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-p...

Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.

PURPOSETo investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma.PATIENTS AND METHODSFifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 m...

Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease

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

A new method for studying splenic reticuloendothelial dysfunction in sickle cell disease patients and its clinical application: a brief report

The low molecular weight cobra venom factor (CoVF) was used to activate the terminal sequence of the alternative complement pathway in thirty-one sera from patients with sickle cell disease (SCD). The SCD sera were compared with normal sera as a source of the alternative complement pathway factors C3 proactivator (C3PA) and C3PA convertase. These factors are required for formation of the enzymatically active CoVF-C3PA complex which is capable of cleaving C3 and thus initiating generation of the cytolytic C5b-9 complex. CoVF cofactor activity was significantly less than normal in SCD sera as measured in an indirect lysis assay, indicating reduced C3PA or C3PA convertase activity in these sera. Qualitative (immunoelectrophoresis) and quantitative (radial immunodiffusion) measurement of C3PA showed, however, that this protein is normal or elevated in SCD sera. Taken together, the reduced CoVF cofactor activity and normal or elevated C3PA in SCD sera suggests that sera from patients with sickle cell disease have reduced C3PA convertase activity.

S Koethe

Papers

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

A new method for studying splenic reticuloendothelial dysfunction in sickle cell disease patients and its clinical application: a brief report

Alternative complement pathway activity in sera from patients with sickle cell disease.