Blocking tumor escape in hematologic malignancies: The anti-PD-1 strategy
Immunotherapy remains an important tool for treatment of hematologic malignancies. The Programmed Death-1 (PD-1) immune checkpoint pathway has emerged as a mechanism of tumor evasion from the anti-tumor immune response. The recent development of anti-PD-1 monoclonal antibodies has offered a targeted approach to cancer therapy. Several agents are in various stages of development and have shown clinical responses across a broad spectrum of both solid and hematologic malignancies. The use of anti-PD-1 therapy in hematologic malignancies is limited but has demonstrated clinical responses in relapsed/refractory disease followin...
Source: Blood Reviews - September 14, 2014 Category: Hematology Authors: Locke J. Bryan, Leo I. Gordon Tags: Review Source Type: research
Biosimilars: A cure to the U.S. health care cost conundrum?
As the cost of healthcare continues to rise and patents on biologics near expiration, biosimilars are gaining visibility as a mechanism for cost reduction. Yet, the introduction of biosimilars into the U.S. market will be complex, due to the related complexity of production, research requirements, and regulatory uncertainty. The purpose of this paper is to frame the relevant issues in order to provide context for stakeholders. It is particularly crucial that clinicians understand the scientific, regulatory, legislative and economic considerations involved in order to ensure that the path to approval is consistent with thei...
Source: Blood Reviews - September 13, 2014 Category: Hematology Authors: Bradford R. Hirsch, Gary H. Lyman Tags: Review Source Type: research
Interferon and tumor necrosis factor as humoral mechanisms coupling hematopoietic activity to inflammation and injury
Enhanced hematopoiesis accompanies systemic responses to injury and infection. Tumor necrosis factor (TNF) produced by injured cells and interferons (IFN) secreted by inflammatory cells are co-products of the process of clearance of debris and removal of still viable but dysfunctional cells. Concomitantly, these cytokines induce hematopoietic stem and progenitor cell (HSPC) activity as an intrinsic component of the systemic response. The proposed scenario includes induction of HSPC activity by type I (IFNα/β) and II (IFNγ) receptors within the quiescent bone marrow niches rendering progenitors responsive to additional s...
Source: Blood Reviews - September 13, 2014 Category: Hematology Authors: Nadir Askenasy Tags: REVIEW Source Type: research
Harnessing the power of alloreactivity without triggering graft-versus-host disease: how non-engrafting alloreactive cellular therapy might change the landscape of acute myeloid leukemia treatment
Human leukocyte antigen-mismatched leukocyte infusions outside of the context of transplantation are a promising strategy for acute myeloid leukemia. Recent studies using such non-engrafting alloreactive cellular therapy (NEACT) revealed that survival of elderly patients increased from 10% to 39% when NEACT was given following chemotherapy, and that durable complete remissions were achieved in about a third of patients with relapsed or chemorefractory disease. We review the clinical reports of different NEACT approaches to date and describe how although T-cell and NK alloreactivity could generate immediate anti-leukemic ef...
Source: Blood Reviews - September 6, 2014 Category: Hematology Authors: Elizabeth F. Krakow, Julie Bergeron, Silvy Lachance, Denis-Claude Roy, Jean-Sébastien Delisle Tags: Review Source Type: research
Blood and marrow transplantation for sickle cell disease: Is less more?
Blood and marrow transplantation is a curative therapy for patients with sickle cell disease yet this option is seldom used. Clinical studies have shown however that children transplanted for this condition can achieve excellent results. In children with sickle cell disease transplanted following conditioning with busulfan, cyclophosphamide, and anti-thymocyte globulin, cure rates in excess of 80% can be obtained when an HLA-matched sibling is used as the donor. However, the large majority of patients with sickle cell disease will not have such a donor, or will not be able to tolerate high dose conditioning regimens. (Source: Blood Reviews)
Source: Blood Reviews - September 4, 2014 Category: Hematology Authors: Javier Bolaños-Meade, Robert A. Brodsky Source Type: research
