Search

Purpose: Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based.Methods: We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor.Results: The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk.Conclusion: Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised. [ABSTRACT FROM AUTHOR]

Patients receiving intensive anti-leukemic treatment or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are prone to develop invasive fungal disease caused by both Aspergillus and non- Aspergillus moulds. Overall mortality following invasive mould disease (IMD) is high; adequate and timely antifungal treatment seems to ameliorate the outcome, yet early diagnosis in the haematological patient remains a challenge for most clinicians. Prophylaxis and the empiric addition of antifungal therapy to neutropaenic patients with fever persisting or recurring during broad-spectrum antibiotic treatment is therefore standard of care in many institutions. However, aside from the potential for overtreatment and important side effects, the emergence of resistance to medical triazoles in Aspergillus fumigatus poses a risk for inadequate initial treatment. Initial voriconazole therapy in patients with azole-resistant invasive aspergillosis was recently shown to be associated with a 23% increased mortality rate compared to the patients with azole-susceptible infection, despite changing to appropriate antifungal therapy once resistance was detected. Moreover, fever is not always present with IMD; therefore, cases may be missed when relying solely on this symptom for starting diagnostic procedures and antifungal treatment. At our institution, a diagnostic-driven treatment approach for IMD was implemented relying on clinical but also laboratory markers to start antifungal treatment. We describe the basis and clinical implementation of our diagnostic-driven approach in this review. [ABSTRACT FROM AUTHOR]

Objective: One explorative observational study in two parts was performed to examine early salivary changes in relation to oral mucositis (OM) in multiple myeloma patients treated with high‐dose melphalan and autologous haematopoietic stem cell transplantation (HSCT). As cryotherapy was introduced after part A as regular care, its effect on OM could be evaluated. Methods: Unstimulated whole‐mouth saliva (UWS) and stimulated whole‐mouth saliva (SWS) were collected, and OM was scored with the Oral Mucositis Nursing Instrument (OMNI) at days −3, 0, 4, 7, 11 and 14 after HSCT. Salivary flow rate, total protein (BCA), mucin 5B, albumin (western blot), total IgA, lactoferrin and myeloperoxidase levels (ELISA) were determined. Results: Trends of decreasing UWS and SWS flow rates and total IgA levels were observed. At days 7 and 11, increases in lactoferrin and albumin levels were found in UWS and SWS. A positive correlation was found between OMNI scores and albumin and lactoferrin levels in SWS (R2 = .56, p = .029 and R2 = .49, p = .043, respectively). In part B, cryotherapy significantly lowered peak OMNI scores. Conclusion: Compositional changes in saliva reflecting inflammation were found in the first days after HSCT, and the use of cryotherapy in the second part was associated with decreased OM severity. [ABSTRACT FROM AUTHOR]

Aims and objectives. The objective of this study was to identify and to assess the quality of evidence-based guidelines and systematic reviews we used in the case of oral mucositis, to apply general quality criteria for the prevention and treatment of oral mucositis in patients receiving chemotherapy, radiotherapy or both. Design. Systematic review. Methods. Literature searches were carried out in several electronic databases and websites. Publications were included if they concerned oral mucositis involving adults treated for cancer and had been published after 1 January 2000. As far as systematic reviews were concerned, the article had to report a search strategy, if the search was minimally conducted in the database PubMed or Medline and the articles included in the review were subjected to some kind of methodological assessment. The Appraisal of Guidelines for Research and Education (AGREE) instrument was used to assess the quality of the guidelines and the Overview Quality Assessment Questionnaire (OQAQ) was used for the quality of systematic reviews. Results. Thirty-one articles met the inclusion criteria of which 11 were guidelines and 20 were systematic reviews. Nine of the 11 guidelines did not explicitly describe how they identified, selected and summarised the available evidence. Reviews suffered from lack of clarity, for instance, in performing a thorough literature search. The quality varied among the different guidelines and reviews. Conclusion. Most guidelines and systematic reviews had serious methodological flaws. Relevance to clinical practice. There is a need to improve the methodological quality of guidelines and systematic reviews for the prevention and treatment of oral mucositis if they are to be used in clinical practice. [ABSTRACT FROM AUTHOR]

Blood concentrations of cyclosporine A (CsA) 800 μg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels 800 μg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels 800 μg/l.Bone Marrow Transplantation (2006) 38, 521–525. doi:10.1038/sj.bmt.1705481 [ABSTRACT FROM AUTHOR]

Mucositis is an inevitable side-effect of the conditioning regimens used for haematopoietic stem cell transplantation. The condition is better referred to as mucosal barrier injury (MBI) since it is primarily the result of toxicity and is a complex and dynamic pathobiological process manifested not only in the mouth but also throughout the entire digestive tract. A model has been proposed for oral MBI and consists of four phases, namely inflammatory, epithelial, ulcerative and healing phases. A variety of factors are involved in causing and modulating MBI including the nature of the conditioning regimen, the elaboration of pro-inflammatory and other cytokines, translocation of the resident microflora and their products, for example, endotoxins across the mucosal barrier, exposure to antimicrobial agents and whether or not the haematopoietic stem cell graft is from a donor. Neutropenic typhlitis is the most severe gastrointestinal manifestation of MBI, but it also influences the occurrence of other major transplant-related complications including acute GVHD, veno-occlusive disease and systemic infections. The pathobiology, clinical counterparts and the means of measuring MBI are discussed together with potential approaches for prevention, amelioration and, perhaps, even cure. Bone Marrow Transplantation (2000) 25, 1269–1278. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about lymphocyte subsets by R. Schmidmaier and colleagues in the June 24, 2011 issue.

Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the severity objectively would be very useful. This will give the opportunity to evaluate studies, to determine risk factors and incidence, and it will make it possible to compare studies. Moreover, this biomarker might improve clinical management for patients. In this paper, we reviewed studies concerning potential biomarkers in blood samples and fecal samples, and potential tests in breath samples and urine samples. We include biomarkers and tests studied in animal models and/or in clinical trials, and discuss the validity, diagnostic accuracy, and applicability. [ABSTRACT FROM AUTHOR]

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34+ hematopoietic stem and progenitor cells (HSPC). This manufacturing process combines amongst others IL15 and IL12 and the aryl hydrocarbon receptor antagonist StemRegenin-1 (SR1) to generate a consistent and active NK cell product that fits the requirements for NK cell immunotherapy well. The cell culture protocol was first optimized to generate NK cells with required expansion and differentiation capacity in GMP-compliant closed system cell culture bags. In addition, phenotype, antitumor potency, proliferative and metabolic capacity were evaluated to characterize the HSPC-NK product. Subsequently, seven batches were manufactured for qualification of the process. All seven runs demonstrated consistent results for proliferation, differentiation and antitumor potency, and preliminary specifications for the investigational medicinal product for early clinical phase trials were set. This GMP-compliant manufacturing process for HSPC-NK cells (named RNK001 cells) is used to produce NK cell batches applied in the clinical trial 'Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL2 in patients with acute myeloid leukemia' approved by the Dutch Ethics Committee (EudraCT 2019-001929-27). [ABSTRACT FROM AUTHOR]

Abstract Introduction Pericatheter calcifications are unusual and rare after removal of indwelling central venous catheters with few reports in the literature. We present a case of a woman with calcifications in her left innominate vein after removal of an implantable venous device. Case presentation A venous access port was surgically placed for intravenous chemotherapy in a 19-year-old Caucasian woman who had been diagnosed with acute lymphoblastic leukemia. She developed a fever three and a half years after placement, and the venous access port was removed as it was seen as the only focus for her fever. In the year following its removal, a computed tomography scan was ordered due to a clinical suspicion of deep venous thrombosis of her left arm. The computed tomography scan revealed a hyperdense structure in the left innominate vein with thrombosis. It was concluded that this was a foreign body, a retained catheter fragment after removal of the catheter. After three-dimensional reconstructions were performed, it was determined that these hyperdense structures were calcifications in the left innominate vein that resembled a foreign body. Conclusions Differentiating between intravenous thrombotic calcification and a retained catheter tip after removal can be challenging, even with modern day diagnostic tools. Care should be taken to document the length of the catheter upon placement and upon removal. In this manner, unnecessary surgical exploration can be avoided. We would like to highlight the importance of these diagnostic considerations for radiologists and oncologists.