Severe acute respiratory distress syndrome coronavirus 2 (COVID-19) is the cause of the current pandemic, which remains a tremendous cause of morbidity and mortality worldwide. Although there are ...numerous trials underway, there is currently no medication known to cure the infection. Nonsteroidal anti-inflammatory drugs (NSAIDs) are inexpensive, widely available medications with antiviral and anti-inflammatory properties and may have utility as an adjunct therapy to improve outcomes in patients with severe COVID-19 infection. A thorough PubMed literature review on the therapeutic use of NSAID was conducted to provide a comprehensive perspective of the role of NSAIDs in treating COVID-19. NSAIDs may be a useful adjunct therapy for patients with severe COVID-19 infection, but further investigation and clinical trials are necessary to ensure their safety and efficacy.
•Quitting smoking after HNSCC diagnosis increases therapy response by about 4-fold.•Quitting after diagnosis reduces cancer recurrence and increases disease-free survival.•Smokers at cancer diagnosis ...who quit before therapy increase long-term survival.•Smoke cessation after cancer is predictive of higher therapy efficacy and survival.
Head and neck squamous cell carcinoma (HNSCC) patients who are current smokers when diagnosed have inferior clinical outcomes compared to never-smokers or previous smokers. However, the impact of quitting after HNSCC diagnosis has not been quantified. In this retrospective, case-control study (n = 134), the odds of complete response to first-line therapy were 3.7 times higher among smokers at diagnosis who quit before treatment initiation (quitters; n = 55) than among those continuing to smoke (p = 0.03). Disease-free survival was also higher among quitters (aHR, 0.33; 95 % CI, 0.12–0.90; p = 0.029). Quitters were 67 % less likely to die of all causes than active smokers (aHR, 0.33; 95 % CI, 0.15–0.71; p = 0.004). These data show for the first time that, smoking cessation after HNSCC diagnosis is predictive of higher therapy efficacy and long-term survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose: To compare rates of common CVC associated complications by type of CVC placed at start of Induction therapy in children treated for newly diagnosed ALL at the Jimmy Everest Center (JEC) at ...the University of Oklahoma Health Sciences Center. Methods: A retrospective chart review analyzed data from newly diagnosed ALL patients treated at the Jimmy Everest Center between 2010-2017. Data was collected on complications including thrombosis, bacteremia, insertion site infection, CVC malfunction and need for removal. Data collection began at the start of Induction and was completed at the end of Induction therapy. Statistical analysis used a univariate and multivariate logistic regression model to compare complication rates between those who had a port versus those who had a PICC placed at start of Induction. Results: Data was collected on 128 patients. Fifty-six patients had a port placed at start of therapy while 72 had a PICC placed. Fourteen percent of patients had a CVC associated complication. Univariate analysis showed no statistically significant difference in rates of CVC associated complications between the groups (Port 16%, PICC 12.5% P=0.564). The rates of hospitalization for CVC associated complications were similar between both groups (Port 14%, PICC 11% P=0.590). Rates of CVC removal were also similar between both groups (Port 4%, PICC 4% P=0.863). Multivariate model that included baseline patient characteristics including type of ALL, patient body surface area, gender, ethnicity and age continued to demonstrate no significant difference in CVC associated complications between both groups. Conclusion: This single institution study showed that there was no significant difference in CVC associated complications between port and PICC line placement at the start of childhood ALL Induction therapy. Port placement can be considered as a safe option at the start of Induction therapy.
Introduction:
Natural killer (NK) cells are large granular lymphocytes, very potent effector lymphocytes that can induce cytotoxicity against a vast array of tumors without the need for antigen ...sensitization or antigen presentation by MHC class I. NK cells are believed to play important role in immune surveillance for cancer, limiting neoplastic progression, and effectors of anti-tumor therapies -by introducing Abs that block NK cell inhibitory receptors yielding improved NK cell-mediated lysis-
Retrospective studies demonstrated a significant correlation of NK cell recovery after autologous stem cell transplantation (ASCT) in multiple myeloma (MM) and disease outcomes. Higher absolute NK cell count one month after ASCT is associated with longer progression-free survival (PFS) and decreased risk of relapse. We aimed at investigating factors affecting NK cell recovery after ASCT in patients with multiple myeloma.
Method:
We designed a prospective cohort study, evaluating the potential factors that could affect NK cell recovery after ASCT. We included participants undergoing frontline ASCT for MM. We excluded participants with non-secretory myeloma or other malignancies that require active treatment, or with autoimmune disorders.
All participants received conditioning regimen consisted of melphalan 200 mg/m2 on day -2. In patients older than 65 years old given 100mg/m2 for 2 days. Dose reduction to 140 mg/m2 for patients with serum creatinine > 2.0 mg/dL. Hematopoietic growth factor (peg-filgrastim 6 mg once subcutaneously) was given on day +1.
Absolute NK cell count (CD3-, CD56+ cells) was determined using flow cytometric immunophenotyping of peripheral blood two-three months after ASCT. To determine variables that affected NK cell recovery after ASCT, absolute NK cell count was dichotomized to less than the lower limit of normal “NK < 76” and normal “NK > or equal 76” following institutional normal reference range which is consistent with ARUP NK cell enumeration reference. Statistical analysis was performed using Fisher-Exact test for categorical variable and Wilcoxon rank test for continuous variables.
Results:
We analyzed the results of fifteen patients treated with frontline ASCT for multiple myeloma. With a median age at diagnosis of 60 years, ranging from 47 - 70 years. Of which 53 percent females and 47 percent males. Patients' baseline characteristics are described in Table 1
Our data showed that 63 percent of patients with post-transplantation ALC > 1000 (5 of 8 patients), and 73 percent for ALC > 500, (8 of 11 patients), had normal absolute NK cell count; with a correlation coefficient of 0.3 (Pearson Correlation Coefficients), suggesting a moderate linear correlation between absolute NK cell count and ALC two-three months after ASCT.
Patients' gender, age at ASCT, and comorbidity index (SORROR score) did not differ between the two groups of patients, P-value= 0.6193, 0.8454, 0.1721, respectively. Additionally, disease burden at the time of diagnosis, presence of CRAB criteria, involved free light chain and monoclonal immunoglobulins; all did not differ between the two cohorts. (Table 2)
Medications received before ASCT did affect the absolute NK cell count with a higher proportion of normal absolute NK cell count, and higher mean absolute NK cell in the cohort received double-class (PI plus IMiDs) when compared to triple-class (PI plus IMiDs plus Anti-CD 38 mAb) therapy before transplantation (mean NK cell count 125 and 53 Cell/μL, respectively), with marginal statistical significance P-value= 0.0667 (Fisher's Exact Test).
Discussion:
Our study showed that the addition of anti-CD38 mAb to myeloma induction regimen, associated with compromised NK cell recovery. Casneuf et al reported similar findings, in daratumumab-treated myeloma patients, total and activated NK-cell counts reduced rapidly in peripheral blood after the first dose, remained low throughout treatment, and recovered after treatment ended. Similar reductions were observed in the bone marrow.
Conclusion:
Medications received before transplantation potentially affect NK cell recovery in multiple myeloma patients. Although, the addition of anti-CD38 mAb to the myeloma induction regimen is associated with deeper response, its impact on immune reconstitution needs to be investigated on a larger sample size.
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No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background: The prevention of cancer and the development of more effective strategies to detect cancer precursor lesions and early-stage cancers remain critical goals. It has been estimated ...that 50% - 60% of cancers could be prevented if known strategies were optimally used. Cancer risk is not uniform, but varies based on age, genetic susceptibility, exposures, existence of preneoplastic conditions across the population. The DNA is constantly damaged by exogenous and endogenous sources. DNA repair mechanisms maintain the integrity of the genome. DNA damage has emerged as a major culprit in tumorigenesis and progression. There are numerous strategies with inherent advantages and disadvantages that may be used for the evaluation of DNA damage and repair. We have developed a novel and highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify DNA damage in p53, the most frequently mutated gene in human cancer. Here, we have extended this assay to HPRT (hypoxanthine-guanine phosphoribosyltransferase), the gene most frequently analyzed in DNA damage studies.
Aim: (1) To quantify the amount of DNA damage in HPRT in peripheral blood cells of never-smokers, smokers, and secondhand smokers. (2) To determine whether cancer patients have higher levels of DNA damage in HPRT than non-cancer patients.
Methods: The assay, PADDA was used on a high-throughput setting to quantify DNA damage (q-PADDA) on the HPRT gene. DNA was extracted and damage was quantified by q-PADDA in peripheral blood cells collected from non-cancer patients never-smokers (n=28), tobacco smokers (n=25), secondhand smokers (n=18), and cancer patients (n=66). Pairwise comparisons in DNA damage among the diverse groups were performed using the Tukey's adjustment in a one-way ANOVA model. Linear regression models were also used to test difference in DNA damage between cancer and non-cancer groups.
Results: Never-smokers, tobacco smokers, and secondhand smokers had similar age distribution. In non-cancer patients, the amount of DNA damage in the HPRT gene in smokers was significantly higher than in non-smokers (p=0.01). Secondhand smokers also showed higher levels of DNA damage than never-smokers but this difference did not reach significance. Among cancer patients (n=64), smokers (n=29) showed significantly higher levels of DNA damage (p=0.03) than non-smokers (n=16).
Conclusion: Our preliminary data document PADDA's ability to quantify DNA damage on HPRT gene. Damage was significantly higher in smokers than never-smokers, both in cancer and non-cancer patients. Application of this assay to a larger population sample has a major potential to establish biomarkers of susceptibility to tobacco-induced cancer, which can guide preventive and diagnostic strategies.
Funding: This work was supported by the NIH, NCI (1R33 CA202898-01, LQ). Dr. Queimado holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology.
Citation Format: Mayilvanan Chinnaiyan, Daniel Brobst, Balaji Sadhasivam, Vengatesh Ganapathy, Sarah E. Johnston, Daniel Zhao, Greg A. Krempl, Lurdes Queimado. DNA damage on HPRT as a biomarker of susceptibility to tobacco-induced cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2075.
In patients with hormone receptor-positive metastatic breast cancer, palbociclib has been shown to improve overall survival and progression-free survival (PFS) when combined with endocrine therapy. ...Dose modification of palbociclib is effective in the management of adverse events. Despite variable clinical response, no predictive biomarkers of efficacy to palbociclib have been identified in metastatic breast cancer. In our study, we aimed to assess the PFS of metastatic breast cancer patients who received dose-reduced palbociclib and compare the results in the non-dose-reduced group. We also evaluated the clinical significance of progesterone receptor (PR) and Ki67 as predictive biomarkers of palbociclib.
Seventy-six palbociclib-treated metastatic breast cancer patients were included in our study. PFS was compared between dose-reduced and non-dose-reduced groups. PR expression and Ki67 status were assessed by immunohistochemistry. Kaplan-Meier method and log-rank test were used to analyze PFS.
Of the 76 patients, 40 (52.6%) experienced dose reduction (DR). Statistical analysis of the results revealed that there were no statistically significant differences observed between dose-reduced (16.5 months) versus non-dose-reduced (17.7 months) patients in PFS (p = 0.5493). For patients with Ki67 ≥14%, PFS was 15.2 months (95% CI: 10.2-22.2 months; p = 0.3024). In patients with PR ≥20%, median PFS was 25.0 months (lower 95% CI: 16.8 months; p = 0.0069).
Our study indicated that DR of palbociclib is frequently required but does not appear to affect PFS. PR expression was suggested to be a significant predictive factor for palbociclib responsiveness.
Natural killer cells are a potent effector lymphocyte subset that can induce cytotoxicity without the need for antigen sensitization or presentation. NK cells are a tempting target –for immune ...therapy, monoclonal antibody, or genetic engineering-to enhance immune surveillance mechanisms against myeloma cells.
We hypothesized an association between natural killer cell recovery after autologous stem cell transplantation (ASCT) and disease outcomes in multiple myeloma patients.
We concluded a prospective study that started enrolling patients in January 2020 to identify the association between absolute NK cell count two to three after ASCT and disease outcomes after autologous stem cell transplantation in multiple myeloma using univariate and multivariate analysis.
Natural killer cell recovery was evaluated during the third month after ASCT, day +60 to +90 post-ASCT. Our patients had a mean NK cell count of 90.53, ranging from 14 to 282 Cell/μL (Std Dev 84.64 Cell/μL). The odds of having a minimal residual disease (MRD-positivity) among patients with partial remission before transplantation is four times higher than patients with very good partial response or better (95% confidence interval 0.45–35.79). Our patients were classified into two groups based on MRD status after ASCT, an MRD-negative group of eight participants and an MRD-positive group of seven participants. The mean absolute NK cell count was significantly higher in the MRD-negative cohort, 131.38 Cell/μL, versus 43.86 Cell/μL in the MRD-positive group (p = 0.049).
We conclude that for multiple myeloma patients treated with ASCT, high absolute NK cell counts two to three months after ASCT is an independent predictor for MRD negativity.
•High absolute NK cell counts two to three months after autologous stem cell transplantation is an independent predictor for MRD negativity.•A moderate linear correlation exists between NK cell count and ALC 60–90 days after transplantation.•The odds of MRD negativity were 7.5 higher for patients with normal absolute NK cells than those with low NK cell count (<76 cell/L; 95% confidence interval 5.21–9.79).•The state of MRD negatively affects immune reconstitution after ASCT potentially due to disrupted bone marrow microenvironment that is affecting both proliferation and effector function of T and NK cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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