Michael L. Linenberger

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence‐based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence‐based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149–162, 2016.

Guidelines on the use of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the american society for apheresis

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the “level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013.

Mylotarg : antibody-targeted chemotherapy comes of age

Mylotarg (gemtuzumab ozogamicin, CMA-676; Wyeth-Ayerst Laboratories, Philadelphia, PA) recently was approved by the US Food and Drug Administration for the treatment of patients with CD33-positive acute myeloid leukemia in first relapse, age 60 years or older, who are not considered candidates for other types of cytotoxic chemotherapy. In combined phase II studies of 142 patients with CD33-positive acute myeloid leukemia in first relapse, Mylotarg monotherapy was associated with a 30% overall response rate. Although treated patients had relatively high incidences of myelosuppression, hyperbilirubinemia, and elevated hepatic transaminases, the incidences of severe mucositis and infections were low compared with what might be expected in association with conventional chemotherapeutic treatment. Preliminary data in pediatric patients also suggest that the immunoconjugate is reasonably well tolerated. Studies of Mylotarg in combination with anthracycline, cytarabine, and agents that inhibit P-glycoprotein are underway.

Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women.

Summary. The inconsistent findings among association studies that have examined the relationship between factor XIIIA Val34Leu and thrombosis may be owing to (1) population differences in the prevalence of other risk factors that modify the association with Val34Leu, or (2) linkage disequilibrium with other functional factor XIIIA polymorphisms. We therefore performed genotyping for factor XIIIA Val34Leu, Tyr204Phe and Pro564Leu in a population‐based study of myocardial infarction (MI) and ischaemic stroke among white women <u200a45‐years of age and 345 demographically similar controls, and examined potential interactions with other risk factors. The presence of the factor XIIIA Leu34 allele was associated with a slight decreased risk of MI [odds ratio (OR)u2003=u20030·80] that was most pronounced among women with traditional cardiovascular risk factors. Paradoxically, women carrying two copies of the Leu34 allele had a nearly fourfold increased risk of ischaemic stroke relative to the Val34/Val34 genotype. Heterozygosity for factor XIIIA Phe204 was associated with a milder increased risk of ischaemic stroke, and analysis of a kindred with congenital dysfibrinogenaemia suggested that co‐inheritance of the factor XIIIA Phe204 allele may increase susceptibility to ischaemic stroke. Our results suggest that the factor XIIIA Val34Leu variant may be associated with a decreased risk of MI among young women with other risk factors. The relationship of factor XIIIA polymorphisms to cerebrovascular disease requires further study.

American Society for Apheresis Guidelines Support Use of Red Cell Exchange Transfusion for Severe Malaria With High Parasitemia

TO THE EDITOR—The American Society for Apheresis (ASFA) Special Issue Writing Committee read the article “Exchange transfusion for severe malaria: evidence base and literature review” by Tan et al with much interest [1]. The article concludes that exchange transfusion (ET) is not indicated in the setting of severe malaria. This recommendation contrasts with our evidence-based review, which supports ET as an adjunctive therapy [2]. Tan et al’s conclusion was based on analysis of cases of severe malaria reported to the US National Malaria Surveillance System from 1985 to 2010, supported by a literature review. They used a propensity score matching technique to select and compare 101 individuals with severe malaria who received ET with 314 who did not. The overall mortality rates of those receiving and not receiving ET were 17.8% and 15.9%, respectively, resulting in no statistically significant association between ET and survival outcomes; however, the study was underpowered to detect a difference in mortality of <10%. The expected difference in the mortality rate between no ET and ET to make it beneficial was set at 4.6% with 15.9% overall mortality. This implies that to consider ET as efficacious, one would need to see a 3-fold decrease in mortality (about 60%). We would like to highlight differences between these 2 publications, and indicate continued support of our conclusion. First, the vast majority of cases reviewed for the Special Issue had severe malaria and >10% parasitemia. By comparison, Tan et al studied cases of malaria infection plus at least cerebral malaria, renal failure, acute respiratory distress syndrome, severe anemia, parasitemia >5%, acidosis, hypotension, or disseminated intravascular coagulopathy. Their Table 1 reports that parasite density was unknown in >90% of cases [1]. Therefore, the assignment of malarial severity was predominantly based on clinical findings, rather than parasitemia. Given the importance of high parasitemia in the decision to perform ET, and in support of the therapeutic rationale of this modality, the effect of ET on mortality cannot be reliably judged in the absence of this pathobiological correlate. Next, there is a lack of important data, including the 38% of cases not having survival data (thus not being included in the study), and exclusion of 5 ET cases that resulted in survival. Last, the Special Issue uses literature published in English only, whereas Tan et al used literature published in multiple languages, utilizing an online translating service of potentially unproven accuracy [3].

Atypical lymphocytes and eosinophilia in primary cytomegalovirus mononucleosis

A 29-year-old woman presented with a three-week history of fever, night sweats, myalgia and rubelliform rash. A full blood count demonstrated leucocytosis: white blood cell count 29 9 10/l with a lymphocyte count of 18 9 10/l and eosinophil count of 4 3 9 10/l. Physical examination did not show lymphadenopathy or hepatosplenomegaly, but prominent axillary, inguinal and mediastinal lymph nodes and splenomegaly were seen on computerized tomography (CT) imaging. A blood film showed numerous atypical lymphocytes and cytologically normal eosinophils (image). Flow cytometric immunophenotyping and T-cell receptor V-beta chain analysis demonstrated an expanded population of polyclonal CD8 T cells, which showed decreased expression of CD5 and CD7 and increased expression of HLA-DR, consistent with a reactive cytotoxic T-cell expansion. A comprehensive autoimmune and infectious evaluation was negative with the exception of positive cytomegalovirus (CMV) immunoglobulin M serology and a CMV viral load of 12 9 10 iu/l. Within 30 days, the patient’s leucocytosis, lymphocytosis and symptoms had resolved, and her eosinophil count normalized within 60 days. Primary CMV mononucleosis is infrequently identified in immunocompetent adults, as most individuals are asymptomatic or have only a mild illness. Polyclonal cytotoxic T cells are stimulated by viral antigen and appear as atypical cells with characteristic increased size (10–25 lm or more in diameter), irregular nuclear contour, fine chromatin and abundant basophilic cytoplasm. Vacuoles and azurophilic granules are variably present. The activated cytotoxic T cells produce interleukin 5 (IL5), which can induce eosinophil proliferation and activation. Although eosinophilia associated with increased IL5 is not commonly reported during acute CMV infection, several such cases have been reported. Flow cytometry can be useful where there is any difficulty in differentiating reactive lymphocytes from leukaemic cells by morphology alone. In immunocompetent adults, primary CMV infection does not require treatment and recovery is expected in 4–6 weeks.