Management of Cancer-Related Anemia with Erythropoietic Agents: Doubts, Certainties, and Concerns

Abstract The management of cancer-related anemia with erythropoietic agents presents many unresolved issues. We reviewed the literature relating to epoetin alfa (Eprex®/Epypo®; Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit®; Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com), epoetin beta (NeoRecormon®; Hoffman-La Roche, Basel, Switzerland, http://www.roche.com), and darbepoetin alfa (Aranesp®; Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) highlighting the results of published clinical trials, safety, and cost-effectiveness. Studies were identified through MEDLINE and the bibliographies of relevant articles. Epoetin alfa, epoetin beta, and darbepoetin alfa have differing pharmacokinetic and pharmacodynamic profiles. They are all effective at reducing transfusion requirements and improving health-related quality-of-life parameters, irrespective of tumor response. A direct comparison between epoetin alfa and darbe poetin alfa is based on limited evidence, which does not allow definitive conclusions about relative efficacy and cost-effectiveness. No predictive factors for response to erythropoietic agents have been validated in prospective trials. The most consistent adverse events are thrombotic and may occur irrespective of an increase in hemoglobin. Recent research indicates that the erythropoietin receptor is expressed in several cancer cell lines, raising the concern of possible stimulation of tumor cell growth by these drugs. Studies on the cost-effectiveness of erythropoietins, particularly compared with transfusion therapy, have been challenging to conduct and analyze and have generated ambiguous results. The use of erythropoietins needs to be optimized in terms of cost-effectiveness, and issues surrounding safety need to be clarified. A stronger methodology for clinical studies and the design of new, randomized, clinical trials is a major priority

The prevention of glucocorticoid‐induced osteoporosis in patients with immune thrombocytopenia receiving steroids:a British Society for Haematology Good Practice Paper

Methodology This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org

Registries in immune thrombocytopenia (ITP) in Europe: the European Research Consortium on ITP (ERCI) network

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Long-Term Outcome of Otherwise Healthy Individuals with Incidentally Discovered Borderline Thrombocytopenia

BACKGROUND: The long-term outcome of individuals with mild degrees of thrombocytopenia is unknown. METHODS AND FINDINGS: In a prospective study conducted between August 1992 and December 2002, 260 apparently healthy individuals with incidentally discovered platelet counts between 100 × 10(9)/l and 150 × 10(9)/l were monitored for 6 mo to determine whether their condition persisted. The monitoring period was completed in 217 cases, of whom 191 (88%) maintained stable platelet counts. These 191 individuals were included in a long-term follow-up study to gain knowledge of their natural history. With a median time of observation of 64 mo, the thrombocytopenia resolved spontaneously or persisted with no other disorders becoming apparent in 64% of cases. The most frequent event during the study period was the subsequent development of an autoimmune disease. The 10-y probability of developing idiopathic thrombocytopenic purpura (ITP), as defined by platelet counts persistently below 100 × 10(9)/l, was 6.9% (95% confidence interval [CI]: 4.0%–12.0%). The 10-y probability of developing autoimmune disorders other than ITP was 12.0% (95% CI: 6.9%–20.8%). Most of the cases (85%) of autoimmune disease occurred in women. CONCLUSIONS: Healthy individuals with a sustained platelet count between 100 × 10(9)/l and 150 × 10(9)/l have a 10-y probability of developing autoimmune disorders of 12%. Further investigation is required to establish whether this risk is higher than in the general population and whether an intensive follow-up results in an improvement of prognosis

Identifying the configurational paths to innovation in SMEs:a fuzzy-set qualitative comparative analysis

Using fuzzy-set qualitative comparative analysis (fsQCA), this study investigates the conditions leading to a higher level of innovation. More specifically, the study explores the impact of inter-organisational knowledge transfer networks and organisations' internal capabilities on different types of innovation in Small to Medium size Enterprises (SMEs) in the high-tech sector. A survey instrument was used to collect data from a sample of UK SMEs. The findings show that although individual factors are important, there is no need for a company to perform well in all the areas. The fsQCA, which enables the examination of the impacts of different combinations of factors, reveals that there are a number of paths to achieve better incremental and radical innovation performance. Companies need to choose the one that is closest to their abilities and fits best with their resources

Antigen receptor rearrangements in the lymphoid malignancies

Various methods for detection of minimal residual disease (MRD) were evaluated in acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and multiple myeloma.Southern blotting was found to be labour intensive, slow, added little additional information to that provided by PCR amplification, and should be replaced in MRD studies by a PCR-based approach. PCR allowed rapid determination of residual disease in all neoplasms studied and, combined with sequencing of amplified PCR products and constructing patient specific oligonucleotides for probing post-treatment samples, was reliable and specific.From the evaluation of patients with ALL, patients up to two years from diagnosis were found to harbour residual tumour in the absence of florid clinical or morphological relapse. In CLL, patients undergoing autologous and allogeneic bone marrow transplantation were assessed using amplification of IgH. After PCR amplification, patient specific probes were constructed using junctional region nucleotides. All patients with CLL undergoing autologous BMT had PCR detectable disease before immunological marrow purging. After purging, disease was detectable in half and autologous marrows. Although PCR detectable disease was present early after transplant in most patients receiving a PCR positive marrow, only those patients in whom persistent or re-emerging PCR positivity was detected demonstrated over clinical relapse. Similar findings were obtained for the allogeneic BMT group; only patients who were found to be persistently positive following transplant had other evidence of disease relapse.Within the myeloma group studied, IgH PCR amplification demonstrated the presence of residual myeloma cells in purged autologous marrow despite the apparent absence of contaminating cells using immunophenotypic analysis.This study confirms the finding of other groups that persistence of disease in ALL may be seen for up to two years following diagnosis. The project also clearly shows that high dose therapy with bone marrow transplantation may be curative in low grade lymphoid malignancies such as CLL.</p