Mucositis involving the gastrointestinal, vaginal, and nasal mucosa is one of the primary dose-limiting toxicities of hematopoietic stem cell transplantation (HSCT) and its conditioning regimen. The oropharyngeal mucosa is commonly affected, which can be detrimental to patient health and quality of life. Despite its significant prevalence and deleterious effects, we have an inadequate understanding of the risk factors and outcomes associated with oral mucositis (OM). We performed a literature search through PubMed and EBSCO (inception to 31 March 2024) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data was extracted from eligible studies using a pre-specified data extraction form. Quality of the data was assessed using the Newcastle-Ottawa Scale for non-randomized, observational studies and the Cochrane Collaboration Tool for randomized controlled trials. Our initial search identified 1677 articles, 34 of which were included in our study. Of those 34, 30 were included in the qualitative assessment of clinical risk factors in the development of OM, and 4 were included in the meta-analysis assessing the relationship between OM and infectious complications following HSCT. Across both HSCT modalities and cancer cohorts, female sex and high-intensity conditioning were common risk factors in the development of OM. When stratified by allogeneic and autologous HSCT, methotrexate, younger age, and longer duration of neutropenia were associated with increased OM risk in allogeneic HSCT recipients, while renal dysfunction, HSV-1 reactivation, and longer neutrophil engraftment were associated with increased OM risk in autologous HSCT recipients. Longer neutrophil engraftment was a common risk factor across different cancer cohorts; however, renal dysfunction was a distinct risk factor for OM in multiple myeloma patients. Additionally, our meta-analysis revealed that patients with OM have an increased risk of developing infectious complications following HSCT compared to those without OM, with an odds ratio of 3.84 (95% CI: 2.51–5.86). The development of OM is related to various risk factors, and individuals with OM are at greater risk of infectious complications. Knowledge of these risk factors and outcomes will help clinicians identify high-risk individuals, prevent OM, and protect an immunocompromised population from subsequent life-threatening complications.

The World Health Organization (WHO) on March 11, 2020, had declared the novel coronavirus disease 2019 (COVID-19) outbreak a global pandemic. The COVID-19 infection continues to be a pandemic and is currently causing overwhelming challenges to healthcare across the nations. Cancer patients represent a unique population vulnerable to COVID-19 infection due to their advanced age, intrinsic frailty, medical comorbidities, immunosuppression, and frequent health care visits for their underlying disease. Robust analysis of COVID-19 infection among cancer patients is crucial to aid in the optimal management of these patients. To identify contributors of worse outcomes in patients with malignancy and COVID-19 and to describe the role of critical care. In this review, we summarized the information from seminal articles on the presentation and management of patients with COVID-19 and malignancy that were published before December 10, 2020. We searched the Pub Med and Medline database for “COVID-19” and “Cancer”, “Malignancy”. Studies published in English, including adults with malignancy and COVID-19 infection, were eligible to be included in this review. Studies on patients that provided details on malignancy, clinical presentation, management, and outcome were included. Various details of malignancy that were included are the site of cancer, histopathological type, stage, chemotherapy, and immunotherapy. Details of COVID-19 infection that were obtained are clinical presentation, the modality of testing, imaging, management, and outcome. Critical care details that were obtained were the type of the organ dysfunction and the requirement of organ support measures, requirement of noninvasive, invasive ventilation, management of vasopressor support, and outcome. Articles that did not have patient details, opinions, letters, and articles not published in English were excluded. All articles were reviewed by 2 independent clinicians. Articles were screened for the above terminologies by independent clinicians. We identified two thousand one hundred eighty-six articles, among which fifty-five were studies that had included patient details pertaining to COVID-19 and cancer (Figure 1). Among these, eighteen studies were eligible and were included in this review as shown in Table 1. A total of 5199 cancer patients were reported. The mean age of patients across all the studies was 64.3 years with male predominance was noted in 12 studies. The clinical presentation and diagnosis of these patients were similar to the general population. Most commonly reported malignancies with COVID-19 infection were hematological in 44% of patients, followed by thoracic malignancy in 11% of patients. The mean number of cancer patients with COVID-19 requiring critical care was 16%. The mean mortality reported was 27.4%. Among the studies that reported the presence of organ dysfunction, respiratory failure was reported in 52% of patients, of which 11.7% required mechanical ventilation. 72% of COVID-19 cancer patients required hospitalization across all the studies. The factors which are associated with the worse outcome from COVID-19 infections among the cancer patients were male gender, age ≥ 65 years, presence of higher comorbidity burden based on Charlson comorbidity index and cumulative illness reporting scale > 6, and smoking history. The majority of the cancer patients required intensive care due to respiratory failure and the need for mechanical ventilation. Appropriate contingency planning for these patients in terms of goals of care and judicious resource allocation in the resource-poor regions is the key. The factors associated with worse outcomes from COVID-19 infections were independent of oncological features such as tumor stage, disease status, or current provision of active anticancer therapy and it could be continued with caution.

Nosocomial infections pose an imminent challenge to hospitalized Coronavirus disease-19 (COVID-19) patients due to complex interplay of dysregulated immune response combined with immunomodulator therapy. In the pre-pandemic era, immunomodulatory therapy has shown benefit in certain autoimmune conditions with untamed inflammatory response. Efforts to recapitulate these immunomodulatory effects in COVID-19 patients has gained impetus and were followed by NIH COVID-19 expert panel recommendations. The current NIH guideline recommends interleukin-6 inhibitors (tocilizumab and sarilumab) and Janus kinase inhibitors (baricitinib and tofacitinib). Several landmark research trials like COVAVTA, EMPACTA, REMDACTA, STOP-COVID and COV BARRIER have detailed the various effects associated with administration of immunomodulators. The historical evidence of increased infection among patients receiving immunomodulators for autoimmune conditions, raised concerns regarding administration of immunomodulators in COVID-19 patients. The aim of this review article is to provide a comprehensive update on the currently available literature surrounding this issue. We reviewed 40 studies out of which 37 investigated IL-6 inhibitors and 3 investigated JAK inhibitors. Among the studies reviewed, the reported rates of nosocomial infections among the COVID-19 patients treated with immunomodulators were similar to patients receiving standard of care for COVID-19. However, these studies were not powered to assess the side effect profile of these medications. Immunomodulators, by dampening the pyrogenic response and inflammatory markers may delay detection of infections among the patients. This underscores the importance of long-term surveillance which are necessary to discover the potential risks associated with these agents.

Background: Newly diagnosed Multiple Myeloma (MM) patients have a 10 to 20 times higher risk of developing venous thromboembolism (VTE) than the general population. The pathogenesis may involve several factors such as activation of procoagulant factors, acquired activated protein C resistance, and inflammation. In addition to the general risk factors for venous thromboembolism such as older age, immobility, and surgery, some MM treatment-related factors such as the use of immunomodulatory drug therapy and abnormal cytogenetics contribute to the increased risk. The PRISM score (Prior VTE, Race, IMiD, Surgery, Metaphase Cytogenetics) is a risk prediction tool for VTE in MM and was published in 2022. The score ranges from 0 to 18 and patients were stratified into three groups: low (0), intermediate (1-6), and high risk (≥ 7). Our primary objective was to assess the external validity of the PRISM score in our community hospital setting. Methods: All consecutive newly diagnosed MM treated at Saint Vincent Hospital from 1/1/2008 to 12/22/2022 were included in our analysis. Patients receiving therapeutic anticoagulation for other indications or a diagnosis of VTE within 6 months preceding the MM diagnosis were excluded. Variables were collected through a retrospective chart review during MM treatment initiation. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Logistic regression was used to calculate the odds ratio (OR) of VTE occurrence in the risk prediction model. Results: A total of 214 patients with newly diagnosed MM and available data on VTE occurrence were included. The median age of our cohort at treatment initiation was 74 years (range 31- 96). The median BMI was 27.8. 56% were male, and 44% were female. The mean PRISM score was 2.9, and 73% of MM were IgG/IgA subtype. IMiD-based induction regimen was used in 63 % of patients. A total of 24 patients (11.2%) were diagnosed with VTE after treatment initiation, of which 8 (3.7%) patients had a previous history of VTE. Prophylactic aspirin was used in 53.8% and abnormal metaphase cytogenetics was identified in 13% of MM cases. The median time to VTE from induction therapy was 4.8 months. The PRISM score was low in 116 patients, intermediate in 89, and high in 9 patients. The AUROC of the model was 0.759 (95% CI, 0.644-0.874) (1). The cumulative incidence of VTE at 6 months, 12 months, and more than 1 year was 6%, 7%, and 11.2% of the patients respectively. Each 1-point increase in the score was associated with a significantly higher chance of VTE occurrence in the model [ HR= 1.53, 95% CI (1.27-1.85), P<0.001]. Among the parameters, patients with a history of VTE [ HR= 1.55, 95% CI (1.26-1.91), P<0.001] and with abnormal metaphase cytogenetics [HR= 2.35, 95% CI (1.37-4.05), P<0.001] had a higher strength of association with the development of VTE after induction (2). Furthermore, among 9 patients with a high-risk PRISM score (≥ 7), 7 (77%) developed VTE within the first 6 months after treatment initiation. Conclusions: Our findings suggest that PRISM [AUROC=0.75, 95% CI (0.644-0.874), P<0.001] score could statistically predict VTE outcomes in our patient population. Abnormal metaphase cytogenetics was a significant predictor of VTE in the validation cohort. Abnormal cytogenetics has been well established to be an indicator of aggressive tumor biology and proliferation in stroma-independent MM. It has been established to be a predictor of VTE in acute myeloid leukemia as well. Also, high-risk scores were predictive of earlier development of VTE after treatment induction. Our study strengthens the evidence of using PRISM as a predictive tool. Further studies are needed to enhance the sensitivity of our existing tool. No relevant conflicts of interest to declare.

Disclosures. No relevant conflicts of interest to declare.