Cellular immunotherapy after allogeneic stem cell transplantation in hematologic malignancies

PURPOSE OF REVIEW: The chimeric state after allogeneic stem cell transplantation provides an ideal platform for adoptive immunotherapy of hematologic malignancies using donor-derived cells. The present review aims to summarize recent results of the transfusion of donor-derived cells with regard to the diseases treated, the cells used for treatment, and the origin of these cells. RECENT FINDINGS: The transfusion of donor lymphocytes has been studied widely, not only in patients with recurrent disease, persistent disease, and mixed chimerism but also in a variety of hematologic malignancies. Donors of lymphocytes and hematopoietic stem cells have been HLA-identical siblings, HLA-matched unrelated donors, and HLA-different haploidentical family members. A variety of cells have been used for adoptive immunotherapy, including plain lymphocytes, selected T cells, T cell lines, and T cell clones. The possible therapies have been expanded by natural killer cells and natural killer T cells as well as antibodies directing the effector cells toward the malignancy. SUMMARY: Adoptive immunotherapy in chimeras has become not only a routine form of treatment of recurrent hematologic malignancy but also a prophylactic measure in high-risk leukemia and lymphoma.     

7A7 MAb: a new tool for the pre-clinical evaluation of EGFR-based therapies

The epidermal growth factor receptor (EGFR) is highly expressed in many types of epithelial tumors. EGFR overexpression has been associated with an advanced stage of the disease, with resistance to standard therapies, and, for certain tumors, with poor patient prognosis. As a result, EGFR has been considered a meaningful target in anti-tumor strategies. Active and passive immunotherapies blocking EGFR and its ligands have been explored. But for successful pre-clinical evaluation of these approaches, well-established murine tumor models are not available and highly desirable. We described, for the first time, the generation and characterization of an anti-murine EGFR extracellular domain monoclonal antibody (7A7 MAb) (IgG1). 7A7 was generated by immunization of Balb/c mice with the recombinant extracellular domain of murine EGFR (rECD-mEGFR). 7A7 recognized an epitope present in the amino acidic core of the antigen and is cross-reactive with the human EGFR. Interestingly, this MAb was able to specifically bind EGFR at the cell surface, allowing the assessment of its differential expression in a panel of murine cells. Noteworthy, in a preliminary immunohistochemical study with 7A7 MAb, recognition of Balb/c mice skin sections and EGFR-positive tumors were observed. We concluded that 7A7 MAb is a valuable tool for EGFR-based therapeutic pre-clinical studies.     

Hidden financial costs in treatment for childhood cancer: an Australian study of lifestyle implications for families absorbing out-of-pocket expenses

PURPOSE: The impact of out-of-pocket expenses on five domains of family lifestyle were explored: social, assets, credit, utilities, and charity. METHODS: Using a cross-sectional survey, 100 parents of pediatric cancer patients reported on the types of out-of-pocket expenses incurred and the perceived lifestyle impact of meeting those expenses. RESULTS: Eighty percent of the sample reported a minimum of five different out-of-pocket expenses (total mean value = 19,064 Australian dollars; approximately 9,723 US dollars). The majority reflected travel, accommodation, and communication costs, use of work-related entitlements, and changes in paid employment. In lifestyle terms, the area of greatest impact was found for the social domain, such as cancelling vacations and giving up recreational pleasures and social expenditure. Those families living furthest from the major cancer treatment center reported the greatest range of out-of-pocket expenses and subsequent lifestyle impact. While there were few differences as a function of cancer type, results suggested that families most vulnerable to financial distress tended to be those whose child had spent relatively longer on treatment. CONCLUSIONS: In meeting out-of-pocket expenses, parents primarily seek ways to "trim the fat" off existing family expenditure. While all families may incur extra expenses, parents of patients located a significant distance from the cancer treatment center remain especially vulnerable (despite increased government allowances). Creative solutions for addressing some expenses may include applications of telemedicine to augment outreach services.     

Negative ELISA D-dimer assay can miss pulmonary embolism

This evaluation of the use of enzyme-linked immunosorbent assay (ELISA) D-dimer test in routine clinical practice supports other evidence that the assay has a high sensitivity to exclude pulmonary embolism in patient populations in which there is clinical suspicion. Nevertheless, the assay incorrectly excluded the diagnosis of pulmonary embolism in 2 cases. Other examples of clinical decision-making exist for which the acceptable negative predictive value for screening is set at 100%--eg, the diagnosis of phenylketonuria in newborns. Physicians who do not want to miss cases of acute pulmonary embolism when they clinically suspect the diagnosis should not rely solely on negative D-dimer assay results when the value to rule out the diagnosis is set at 500 ng/mL. If a lower value is used to define normal--eg, 250 ng/mL, as used in other studies-no cases of acute pulmonary embolism would have been missed in this group of patients. Regardless of the cutoff used, the assay will yield many false-positive results.     

Assessing the effects of substance abuse among applicants for TANF benefits: the outcome of a demonstration project in Florida

This paper examines an attempt by the State of Florida to devise a mechanism for determining the level of drug use among TANF recipients and to determine the extent to which such use affects employment, earnings and use of government services by TANF beneficiaries. Data from tests administered by substance abuse testing providers were combined with information from Medicaid, Food Stamp, cash assistance and Unemployment Insurance files to examine differences between the two groups. The findings suggest that the procedures employed by the State of Florida did not produce reliable estimates of the level of drug use among TANF beneficiaries. The data did show very small differences in employment, earnings, and use of government services between individuals who tested positively and those who tested negatively for substance abuse. In addition, evidence is presented that suggests that there is very little difference in employment, earnings and use of government services between users of different kinds of drugs.