New therapies in onco-hematology and new infectious risk factors.

Abstract

The biologic, clinical and therapeutic setting is nowadays such that risk factors for infectious complications are constantly changing and progressively increasing in patients suffering from onco-hematologic conditions. In addition to situations that are well known or that are gradually being recognized related both to the underlying disease and to treatment, such as neutropenia, neutrophil dysfunction, mucosal damage, concomitant monocytopenia and lymphopenia, abnormalities within the host cellular and humoral compartments, impairments in cytokine networks, alterations in T lymphocytes/tumor interactions, crosstalks between neoplastic cells and accessory cells, etc, over the last few years we are witnessing important changes in the overall management of patients with hematologic malignancies. Historically, the categories at risk were represented by patients with acute leukemia and patients undergoing an allogeneic stem cell transplant. In both, the likelihood of eradicating the disease requires necessarily a myeloablative therapeutic strategy, complicated in the allografted patients by the risks of graft-versus-host disease (GvHD), the required immunosuppressive treatment and the recently documented role that cytokines may play in the development of acute GvHD. Considerable changes have occurred in recent years. From the identification of "new" diseases at risk (e.g. lymphomas occurring in HIV+ individuals), to the progressive and constant increase in allotransplant procedures, to the development of new transplant procedures (cord blood, matched-unrelated or mismatched donor transplant, mini-transplant, the administration of donor lymphocytes), to the development of new drugs that can induce immunosuppression, to the clinical use of certain monoclonal antibodies (MoAb), to the combined use of chemotherapy plus MoAb. These developments are associated with other general considerations. Within these: 1) the growing use of ablative therapies in diseases for which for many years the approach has been less aggressive or indeed conservative; 2) the progressive recognition of categories of patients with unfavorable prognosis for whom an aggressive approach is required; 3) the constant improvement in mean life expectancy and "biologic" age of patients; thus, the progressive changes in the definition of "old age". Taken together, this has led, on the one hand, to an increase in the categories of onco-hematologic patients at risk of infective complications and to a major focus on the immune compartment of the affected patients, and, on the other hand, to an overall broadening of the infective scenario.