Immunotherapy of Leukemia

Both Autologous and Allogeneic immune therapies are of interest for control of these diseases.

Autologous Immunotherapy is being expored in trials evaluating the combination of GM-CSF and interferon administered to patients with indolent myeloid disorders. The combination of GM-CSF and interferon has recently been shown to effectively drive the dendritic cell differentiation of monocytes in vitro. Given that many patients with these disorders have malignant or clonal monocytes circulating, it is expected that the co-administration of these two cytokines should potentially drive in vivo dendritic cell differentiation which may be therapeutically useful. Patients with early chronic phase CML, MDS and MPD (polycythemia vera, essential thrombocythemia, and myelofibrosis) will be enrolled. Blood and skin biopsies will be examined for DC populations before and after treatment. Flow cytometric assessment of circulating immune cells will include four color assessment of dendritic cells and intracellular cytokine analysis of effectors.

Laboratory optimization of anti-leukemic activity: Highly variable DC maturation has been seen in clinical and preclinical data accrued to date. The recent observation that interferon alpha may significantly contribute to DC differentiation and functional activation is important for this field given its commercial availability as a clinical grade reagent. We will continue to systematically study patient cells with a view to developing simpler and more effective techniques for the in vivo differentiations of these cell populations to therapeutically useful dendritic cell populations. Autologous T-cell proliferation, elispot, and cytotoxicity assays and multiparametric flow cytometry will provide biological endpoints for these studies .

Allogeneic immunotherapy is being studied in the context of trials of non-myeloablative stem cell transplantation as therapy for advanced hematological malignancies. To date nearly 50 patients have been enrolled on such trilas here at HMC. Some remarkeable therapeutic successes have been seen, including remissions of >1year in patients with chemotherapy refracotry acute leukemias.

An extensive collection of cryopreserved leukemias is available and is used for laboratory studies. These are available to other HMC investigators after appropriate regulatory documents are executed.