A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, ...pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed.
There are currently a number of licensed azole antifungal drugs; however; only 4 (namely, fluconazole, itraconazole, posaconazole, and voriconazole) are used frequently in a clinical setting for ...prophylaxis or treatment of systemic fungal infections. In this article, we review the pharmacokinetic interactions of these azole antifungal drugs with other coadministered agents. We describe these (2-way) interactions and the extent to which metabolic pathways and/or other supposed mechanisms are involved in these interactions. This article provides an overview of all published drug-drug interactions in humans (either healthy volunteers or patients), and on the basis of these findings, we have developed recommendations for managing the specific interactions.
Background. Intensive treatment of hematological malignancies with hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence of opportunistic invasive fungal infection, but ...individual risk varies significantly. Dectin-1, a C-type lectin that recognizes 1,3-β-glucans from fungal pathogens, including Candida species, is involved in the initiation of the immune response against fungi. Methods. Screening for the DECTIN-1 Y238X polymorphism within a group of 142 patients undergoing HSCT was correlated with Candida colonization and candidemia. Furthermore, functional studies were performed on the consequences of the polymorphism. Results. Patients bearing the Y238X polymorphism in the DECTIN-1 gene were more likely to be colonized with Candida species, compared with patients bearing wild-type DECTIN-1, necessitating more frequent use of fluconazole in the prevention of systemic Candida infection. Functional assays demonstrated a loss-of-function phenotype of the polymorphism, as shown by the decreased cytokine production by immune cells bearing this polymorphism. Conclusions. The Y238X polymorphism is associated with increased oral and gastrointestinal colonization with Candida species. This suggests a crucial role played by dectin-1 in the mucosal antifungal mechanisms in immunocompromised hosts. The finding that DECTIN-1 polymorphisms rendered HSCT recipients at increased risk for fungal complications may contribute to the selection of high-risk patients who should be considered for antifungal prophylaxis to prevent systemic candidiasis.
Stem cell transplantation (SCT) is still complicated by the occurrence of fever and inflammatory complications attributed to neutropenia and subsequent infectious complications. The role of mucosal ...barrier injury (MBI) of the intestinal tract therein has received little attention.
We performed a retrospective analysis in 163 SCT recipients of which data had been collected prospectively on intestinal damage (citrulline), inflammation (C-reactive protein), and neutrophil count. Six different conditioning regimens were studied; 5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model multivariate and AUC analyses were used to define the role of intestinal damage in post-SCT inflammation. We also studied the relationship between the degree of intestinal damage and the occurrence of early post-SCT complications.
In the 5 MA regimen there was a striking pattern of inflammatory response that coincided with the occurrence of severe intestinal damage. This contrasted with a modest inflammatory response seen in the NMA regimen in which intestinal damage was limited. With linear mixed model analysis the degree of intestinal damage was shown the most important determinant of the inflammatory response, and both neutropenia and bacteremia had only a minor impact. AUC analysis revealed a strong correlation between citrulline and CRP (Pearson correlation r = 0.96). Intestinal damage was associated with the occurrence of bacteremia and acute lung injury, and influenced the kinetics of acute graft-versus-host disease.
The degree of intestinal damage after myeloablative conditioning appeared to be the most important determined the inflammatory response following SCT, and was associated with inflammatory complications. Studies should explore ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce complications associated with myeloablative conditioning therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Haematopoietic stem cell transplantation (HSCT) is potentially lifesaving. However, it comes with negative consequences such as impaired physical functioning, fatigue and poor quality of ...life. The aim of this systematic review and meta-analysis is to determine the effect of exercise and nutrition interventions to counteract negative consequences of treatment and improve physical functioning in patients receiving HSCT.
Methods
This systematic review and meta-analysis included randomised controlled trials from three electronic databases between 2009 and 2020. The trials included adult patients receiving HSCT and an exercise or nutrition intervention. Study selection, bias assessment and data extraction were independently performed by two reviewers. Physical functioning outcomes were meta-analysed with a random-effects model.
Results
Thirteen studies were included using exercise interventions (
n
= 11) and nutrition interventions (
n
= 2); no study used a combined intervention. Meta-analysis of the trials using exercise intervention showed statistically significant effects on 6-min walking distance (standardised mean difference (SMD) 0.41, 95% CI: 0.14–0.68), lower extremity strength (SMD 0.37, 95% CI 0.12–0.62) and global quality of life (SMD 0.27, 95% CI: 0.08–0.46).
Conclusion
Our physical functioning outcomes indicate positive effects of exercise interventions for patients receiving HSCT. Heterogeneity of the exercise interventions and absence of high-quality nutrition studies call for new studies comparing different types of exercise studies and high quality studies on nutrition in patients with HSCT.
Purpose
To explore trends over time in admission prevalence and (risk-adjusted) mortality of critically ill haematological patients and compare these trends to those of several subgroups of patients ...admitted to the medical intensive care unit (medical ICU patients).
Methods
A total of 1,741 haematological and 60,954 non-haematological patients admitted to the medical ICU were analysed. Trends over time and differences between two subgroups of haematological medical ICU patients and four subgroups of non-haematological medical ICU patients were assessed, as well as the influence of leukocytopenia.
Results
The proportion of haematological patients among all medical ICU patients increased over time odds ratio (OR) 1.06; 95 % confidence interval (CI) 1.03–1.10 per year;
p
< 0.001. Risk-adjusted mortality was significantly higher for haematological patients admitted to the ICU with white blood cell (WBC) counts of <1.0 × 10
9
/L (47 %; 95 % CI 41–54 %) and ≥1.0 × 10
9
/L (45 %; 95 % CI 42–49 %), respectively, than for patients admitted with chronic heart failure (27 %; 95 % CI 26–28 %) and with chronic liver cirrhosis (38 %; 95 % CI 35–42 %), but was not significantly different from patients admitted with solid tumours (40 %; 95 % CI 36–45 %). Over the years, the risk-adjusted hospital mortality rate significantly decreased in both the haematological and non-haematological group with an OR of 0.93 (95 % CI 0.92–0.95) per year. After correction for case-mix using the APACHE-II score (with WBC omitted), a WBC <1.0 × 10
9
/L was not a predictor of mortality in haematological patients (OR 0.86; 95 % CI 0.46–1.64;
p
= 0.65). We found no case–volume effect on mortality for haematological ICU patients.
Conclusions
An increasing number of haematological patients are being admitted to Dutch ICUs. While mortality is significantly higher in this group of medical ICU patients than in subgroups of non-haematological ones, the former show a similar decrease in raw and risk-adjusted mortality rate over time, while leukocytopenia is not a predictor of mortality. These results suggest that haematological ICU patients have benefitted from improved intensive care support during the last decade.
Mucositis and Infection in Hematology Patients Blijlevens, Nicole M A; de Mooij, Charlotte E M
International journal of molecular sciences,
05/2023, Letnik:
24, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and ...debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advances in our understanding of the relation of mucositis and infection.
Summary
Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as ...‘febrile neutropenia’, but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or ‘mucositis’. MBI creates a port‐de‐entrée for resident micro‐organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host‐microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept ‘febrile neutropenia’ alone may no longer suffice and a new concept ‘febrile mucositis’ should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host‐microbe interactions arising from cytotoxic therapy‐induced tissue damage in order to reduce fever in neutropenic patients with cancer.
We assessed stage-specific trends in primary therapy and relative survival among adult follicular lymphoma (FL) patients diagnosed in the Netherlands between 1989-2016 (N = 12,372; median age, 62 ...years; and 21% stage I disease). Patients were stratified by disease stage and subsequently categorized into four calendar periods (1989-1995, 1996-2002, 2003-2008, and 2009-2016) and three age groups (18-60, 61-70, and >70 years). The use of radiotherapy in stage I FL remained relatively stable over time and across the three age groups (i.e., 66%, 54%, and 49% in 2009-2016, respectively). In stage II-IV FL, the start of chemotherapy within 12 months post-diagnosis decreased over time, indicating a broader application of a watch-and-wait approach. Relative survival improved considerably over time, especially since 2003 when rituximab was introduced in the Netherlands, and for stage III-IV FL patients and older age groups. Five-year relative survival for patients with stage I-II versus stage III-IV FL in the period 2009-2016 was 96% versus 90%, 93% versus 83%, and 92% versus 68% across the three age groups, respectively. Collectively, the improvement in survival since 2003 is accounted for by advances in FL management, particularly the implementation of rituximab. There remains, however, room for improvement among elderly stage III-IV FL patients.
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