Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

[Focus on academic multicenter trials: impact of the German drug law on hematological/oncological therapy optimization trials]. / Akademische multizentrische Studien im Fokus: Auswirkungen der Arzneimittelgesetzgebung auf Therapieoptimierungsstudien in der Hämatologie/Onkologie.

BACKGROUND: The purpose of this study was to evaluate the effect of legal regulations for clinical trials on study centers participating in investigator-initiated trials (IITs) in the field of hematology/oncology. METHOD: Questionnaires were sent out to the heads of hematology-oncology study centers. RESULTS: Medical units participating in IITs have a good infrastructure and extensive experience in clinical trials. Depending on indication, a high proportion of patients have been treated in studies with the purpose to improve outcome. However, 35% of the responders will reduce their participation in IITs in the future due to a lack of financial support for staff involved in the extensive organizational tasks. CONCLUSIONS: The widely recognized research field in therapy optimization trials in hematology and oncology in Germany is at risk. This will have negative effects on the patients as highly sophisticated protocols will no longer be initiated in several study centers, resulting in the loss of valuable data for the improvement of patient therapy and outcome. To stop this development, legislators as well as regulatory authorities and health insurances need to make the necessary changes in the legal framework.

SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma.

In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).

Antimicrobial therapy of febrile complications after high-dose chemotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

More than 18,000 autolgous transplantation were performed in Europe in the year 2009. It as a routine procedure in experienced centres. Even if there is a low mortality rate, infections are a major issue after transplantation, occurring in more than 60 % of the patients. In this review we discuss all aspects of infections after autologous stem transplantation, including epidemiology, diagnostics, therapeutic algorithms, prophylaxis and supportive therapy.

The Financial Effect of Medicare Coverage Design and Safety Net Options for Cancer Care.

BACKGROUND: National spending on specialty medications accounted for approximately $193 billion in 2016. The coverage design for Medicare Parts B and D has shifted medication costs to patients, which may prohibit patients from starting or maintaining therapy due to affordability. As a result, patients have enrolled in safety net financial options, such as patient assistance and foundation programs. Safety net options may provide savings not otherwise realized by Medicare; however, they may have a negative financial effect on health systems and pharmaceutical manufacturers. OBJECTIVES: To (a) quantify financial savings to Medicare as a result of patient enrollment in patient assistance programs and (b) quantify the financial effect of safety net options for patients, manufacturers, and the academic medical center that participated in this study. METHODS: A single-center, nonrandomized, retrospective pilot study of Medicare beneficiaries was conducted. Patients who were prescribed hematology/oncology specialty medications and enrolled in safety net options between July 2015 and June 2017 were included. Investigators collected data related to fill history, drug cost, and prescription coverage. The primary outcome was the overall cost savings to Medicare as a result of patient enrollment in patient assistance programs. Secondary outcomes included total patient out-of-pocket savings as a result of foundation copayment support, financial effect on manufacturers as a result of patient assistance programs, and health system revenue impact as a result of safety net options. Descriptive statistics were used. RESULTS: This study included 114 patients. Medicare saved $5,083,816.83 over 2 years as a result of patient assistance programs. Eight foundations provided $240,350.04 in patient insurance copayments. Nine manufacturers provided 2,243 free drug doses, valued at $3,379,032.34. The participating medical center missed the opportunity for $6,481,543.55 in revenue due to patient assistance programs. CONCLUSIONS: The participating medical center's efforts to improve access to oncology care took considerable time and resources. These activities, as well as unreimbursed infusion services, were costs to the medical center that may not be recognized by Medicare. Manufacturers also supported patient access through their sponsored patient assistance programs. The use of these services and safety net options resulted in cost savings to Medicare and their beneficiaries. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Findings from this study were part of a podium research presentation at the Great Lakes Pharmacy Residency Conference; April 25, 2018; West Lafayette, IN.

[Role of multicenter study groups for clinical research in hematology and oncology]. / Bedeutung von Multicenterstudiengruppen für die klinische Forschung in der Hämatologie und Onkologie.

During the past 25 years a highly effective infrastructure for clinical trials was developed in hematology. Following initial funding by the BMFT (Ministry for Research and Technology) a number of large multicenter study groups for leukemia and lymphoma were developed. Treatment results from these studies often represent the"gold standard". However, since no standard therapy is defined for these diseases, the study groups aim to treat all patients within treatment optimization trials (TOT) to combine research and care. They contribute considerably to quality control in therapy and diagnostics, e.g., by establishing central reference laboratories. The regulatory requirements for clinical trials were extended considerably after the activation of the 12th drug law and TOTs now have to fulfill requirements similar to registration trials in the pharmaceutical industry. Due to the considerable bureaucratic effort and increased costs, only few large multicenter trials could thereafter be initiated and a substantial disadvantage for independent academic research becomes clearly evident.

Medical devices; hematology and pathology devices; classification of cord blood processing system and storage container. Final rule.

The Food and Drug Administration (FDA) is classifying a cord blood processing system and storage container into class II (special controls). The special control that will apply to this device is the guidance document entitled "Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Container." FDA is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of this device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for this device.

Compliance with the Clinical Laboratory Improvement Amendments of 1988 for hemoglobin screening--California, 1995.

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) established standards for improving the quality of clinical laboratory testing in the United States. One intent of CLIA was the regulation of smaller, provider-based laboratories, such as those operated by health-care providers in the Child Health and Disability Prevention (CHDP) program. In 1995, in conjunction with an assessment of county-specific variations in prevalence rates of anemia, the California Department of Health Services conducted a mail survey of CHDP providers to assess compliance with CLIA regulations for hemoglobin screening. This report summarizes the results of that survey, which indicate that, in California, many CHDP providers do not comply with CLIA-mandated quality-assurance practices for hemoglobin screening in their clinical laboratories.

Transfusion medicine technology transfer: traps to avoid.

Technology transfer is the process of commercializing technology and taking it from the laboratory to the marketplace. At some stage in the technology transfer process, a due diligence will be undertaken. A due diligence is an enquiry into the technology and, in particular, its ownership. Research organizations including hospitals, universities, and blood banks need to own the intellectual property that they seek to commercialize. They own the intellectual property created by their staff in the course of employment. But volunteers, students, and collaborators, not being members of staff, will own the intellectual property that they create. This gives rise to due diligence and ownership defects, when intellectual property may in fact be owned by someone other than the research organization that seeks to commercialize it. Joint ownership can sometimes prevent commercialization. An assignment of intellectual property from a volunteer or student may sometimes be required. Such an assignment, if it inadequately deals with all relevant issues, may be void pursuant to laws throughout the world. A void deed of assignment may expose the research organization to legal liabilities. The categories of technology transfer traps to be explored are (1) ownership issues arising from the participation of students and volunteers in research, (2) ownership issues arising from collaborative research relationships, (3) ownership issues arising from the participation in research of visitors from another research organization, and (4) ownership issues arising from inventions made by employees. Each of these is considered in the context of the legal and regulatory framework in Australia, Canada, the United States of America, and the United Kingdom.

Informed consent: issues for providers.

Although obtaining informed consent is an important part of the hematologist/oncologist's practice, understanding the legal consequences can assist the practitioner to understand why it is necessary to disclose as much information as he or she does. By following the standard of care used in the state of practice, the physician can decrease the risk of being sued by patients for lack of informed consent, thus fulfilling his or her legal and ethical duties by providing the patient with all the information necessary to make an informed decision.

Regulating hematology/oncology research involving human participants.

The conduct of hematology/oncology research, particularly clinical trials involving human participants, is an extensively regulated enterprise. Professionals in the specialty of hematology/oncology have important stakes in the success of biomedical research endeavors. Knowledge about and compliance strategies regarding the pertinent regulatory parameters are essential for avoiding negative legal repercussions for involved professionals. At the same time, there is a need to be aware of and actively resist the danger that strong [legal] protectionism might inadvertently result in undermining physician investigators' sense of personal moral responsibility in the conduct of human experiments. For all the limitations of that virtue in the protection of human subjects, it is surely not one that we would want medical scientists to be without [47]. Members of the potential participant pool, financial sponsors, and the general public must be convinced that everyone involved in the research enterprise is committed to operating within acceptable legal and ethical boundaries if the atmosphere of confidence and trust that is indispensable to the continued process and progress of investigation aimed at extending and improving quality of life for all of us in the future is to continue and flourish [48].

[Evaluation of schistocytes measurement guidelines]. / Évaluation de recommandations concernant l'identification et la numération des schizocytes : une enquête du Groupe francophone d'hématologie cellulaire.

The schistocytes are fragmented red blood cells mainly observed in the setting of hemolytic anemias and particularly among the thrombotic microangiopathies. The presence of schistocytes is an important criterion for the diagnosis of mechanical anemias, though the identification of these cells remains problematic. As a high variability of the morphologic identification criteria of the schistocytes among morphologists has been observed, some guidelines have been proposed after workshops (French and Italian groups). The International council for standardization in hematology published a consensus in November, 2011. The French group of cellular hematology (GFHC) aimed to recover the opinion of French biologists directly confronted to schistocytes measurements. 169 out 500 (34%) answered 10 questions dealing with the identification and measurements of schistocytes as proposed by the ICSH guidelines. A consensus was reached for the urgent need of guidelines documents, moreover in the current background of the European accreditation NF EN ISO 15189 rules. A traduction in native (French) language as warmly wished in order to facilitate the diffusion of the information. New fragmented red cell parameter recently provided by 2 manufacturers of automated blood cell counters remained doubtfull for routine use for half of the biologists.

Legal and ethical issues relating to use of complementary therapies in pediatric hematology/oncology.

Pediatricians increasingly are asked to advise pediatric patients and their families concerning integration into conventional care (including hematology and oncology) of complementary and alternative medical (CAM) therapies such as chiropractic, massage therapy, and herbal medicine. Inclusion of CAM therapies in pediatric oncology and hematology--as in any medical subspecialty--is not itself "unethical," clinically inadvisable, or legally risky; the danger comes from over-reliance on one or more CAM therapies (particularly those with evidence of danger and/or paltry evidence of success) to the exclusion of conventional care that is curative and imminently necessary. Pediatricians can help address potential malpractice liability issues by evaluating the level of clinical risk, engaging the patient in shared decision making and documenting this in the medical record, continuing to monitor conventionally, and being prepared to intervene conventionally when medically required.

Juridical and liability reflexes of bone marrow processing.

Author analyzes bone marrow processing procedures and points out juridical and forensic-medicine reflexes of this therapeutical act. The aspects of informed consent and professional liability of hematologist are clarified.