•High CD4 count does not necessarily protect against aggressive AIDS-defining diseases, particularly, HIV-associated Kaposi sarcoma.•Extremely elevated HHV-8, HIV, and EBV viral loads could predict ...aggressive HIV-associated KS disease course.•Anemia and thrombocytopenia in HIV/AIDS could be autoimmune like ITP and AIHA or bone marrow infiltration-related, by Kaposi sarcoma, for instance, or both.
Bone marrow infiltration by Kaposi sarcoma (KS) in human immunodeficiency virus (HIV) patients is rare, with only a few cases reported in patients with a CD4 count greater than 200 cells/ml. To the best of our knowledge, this is the first reported case of bone marrow involvement in HIV-associated KS in which the CD4 count is greater than 400 cells/ml. In this article, we present a patient with HIV-associated KS with skin, lymph node, bone, pulmonary, gastrointestinal, and bone marrow involvement despite a high CD4 count. This is the highest CD4 count associated with bone marrow invasion in the medical literature. A high CD4 count does not protect untreated HIV patients against aggressive, diffuse KS-related lesions, including bone marrow infiltration.
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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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e18630
Background: Studies have reported elevated mortality in HIV patients (pts), including cancer-specific mortality, compared to non-HIV pts. However, many of these studies did not ...include data from Louisiana. Louisiana has among the highest HIV and AIDS case rates in the country, but there is no available large-scale data regarding cancer outcomes in HIV pts in the state. We compared our data in Louisiana to the largest known study to date over an expanded time period to evaluate for disparities. Methods: Following linkage of Louisiana Tumor Registry data from 1995-2016 and Louisiana Office of Public Health, STD/HIV Program database, we identified a total of 435,478 cancer cases, of which 2,949 were HIV-positive (0.67%). Analyses of categorical variables were performed using Pearson’s chi-squared test. Cause of death was extracted from death certificate or autopsy report. Survival analyses were performed utilizing SEER*Stat. Results: Despite the higher proportion of HIV in cancer pts in Louisiana, demographics are similar to previously published data in that cancer pts with HIV tended to be male, black, and younger than their HIV-negative counterparts (p<0.001). However, although 5-year survival was substantially decreased in HIV-cancer pts in congruence with other studies, cancer-specific mortality was lower than non-HIV pts in all cohorts, including both AIDS-defining cancers (ADC) and non-AIDS-defining cancers (non-ADC). Conclusions: HIV infection in cancer pts in Louisiana is associated with lower survival but not increased cancer-specific death, independent of race, gender, age, ADC vs non-ADC, and viral vs non-viral etiology. HIV-related deaths still comprise a substantial cause of death in this population.Table: see text
e18732
Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A ...study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status; 2) assess the relative risk of VTE due to COVID-19 in cancer patients; 3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) RR 3.45, 95% CI 1.85-6.67. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.
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2627
Background: There are increasing reports of thromboembolic complications in patients with COVID-19 infection. According to a meta-analysis of 28,173 patients, the prevalence of ...venous thromboembolism (VTE) in hospitalized COVID-19 patients ranges from 7.9% to 22.7% based on the severity of COVID-19. Cancer and anti-cancer therapies are known risk factors for thrombosis. Another study based on registry data reported the overall prevalence of VTE in hospitalized COVID-19 patients with cancer to be 14.5%. Our study aimed to assess the prevalence of VTE in cancer patients diagnosed with COVID-19 as well as the association between VTE and cancer in the setting of COVID-19 infection in a large predominantly urban healthcare system. Methods: We utilized a cohort data query tool in the electronic medical record at University Medical Center in New Orleans, Louisiana to identify patients >17 years of age with a hospital or clinic visit in the LCMC Health system between March 1, 2020 and December 31, 2020 which were considered the base population for the study. Cancer patients were identified via the cancer registry tool. Patients with COVID-19 were identified using the abnormal COVID-19 PCR test result search field. An encounter diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) was used to identify patients with VTE. Odds ratios, p-values, and corresponding confidence intervals (CI) were calculated using 2x2 contingency tables. Results: In our database, we identified 3,807 patients with a diagnosis of COVID-19 and 9,560 with a cancer diagnosis. 158,812 patients had neither COVID-19 nor cancer. There were statistically significant greater odds of developing VTE in all subgroups compared: COVID-19 alone vs neither (OR 2.43), cancer alone vs neither (OR 3.8), and COVID-19 and cancer vs neither (OR 10.65). Conclusions: COVID-19 and cancer are both risk factors for VTE. Based on our study, appears that cancer has the greater effect on VTE compared with COVID-19 infection. Also, there is possibly a synergistic effect between COVID-19 and cancer, which further increases the likelihood of VTE. This study is a preliminary analysis. Further investigation is warranted in the form of either variable adjusted analysis of the same data, individual chart review, or a prospective study.Table: see text
Background: Patients (pts) with classical Hodgkin Lymphoma (cHL) who become refractory to both BV and anti-PD-1 therapies (double refractory, DR) or intolerant (INT) of BV and anti-PD-1 therapies ...have limited treatment options. There is limited information regarding optimal treatment approaches in these pts. Rechallenging with BV or anti-PD-1 therapies has been previously described in small cohorts with variable success. Allogeneic stem cell transplantation (alloSCT) remains the only curative approach in multiply relapsed/refractory cHL. This study aims to assess practice patterns and outcomes in a large cohort of pts with DR or INT cHL. Methods: We conducted a retrospective study of adult pts with cHL from 14 U.S. academic medical centers who developed DR or INT cHL between Jan 2011 and Dec 2021. DR was defined as treatment failure (evidence of progression by imaging or biopsy) while on therapy or within 3 months of the last dose of both BV and anti-PD-1 therapy. INT was defined as having toxicity limiting further cycles of BV or anti-PD-1 therapy. Pts with INT were either intolerant to both BV and anti-PD-1 or intolerant and refractory to BV or anti-PD-1. The co-primary endpoints were progression free survival (PFS) and overall survival (OS) in pts with DR/INT cHL. Time-to-event analyses were evaluated by Kaplan-Meier methods and log-rank tests. Results: A total of158 pts were eligible. Clinical characteristics at diagnosis included median age 33 years (yrs, range 16-89), 61% male, 77% white race, 66% nodular sclerosing subtype, 47% stage 4, and 60% primary refractory. DR cHL was observed in 119 pts (75%), while 39 pts (25%) were INT. The median OS from the time of DR/INT was 7.4 yrs (95%CI 4.1-NR). There was no difference in OS by DR and INT pts (log-rank p=0.33). The majority (87%, n=137) received subsequent lines of therapy after DR/INT (median 2, range 0-14). Next line of therapy after DR/INT was BV or anti-PD-1 rechallenge (with or without combination therapy) in 39 pts (29%), conventional cytotoxic chemotherapy in 62 pts (45%), immunomodulatory based therapy (lenalidomide, everolimus) in 16 pts (12%) or other in 20 pts (15%). Any line of therapy after DR/INT included alloSCT in 29 pts (18%) and CD30 directed chimeric antigen receptor T-cell (CART) therapy in 24 pts (15%). Forty pts (25%) were rechallenged with BV based therapies. The majority (88%) were previously refractory to BV. The median time from DR/INT to BV rechallenge was 348 days (range 14-1186). The objective response rate (ORR) was 63%, complete response rate (CRR) was 33%, and median PFS was 183 days (95%CI 108-273). Fifty-nine pts (37%) were rechallenged with anti-PD-1 based therapies. The majority (88%) were previously refractory to anti-PD-1 therapy. The median time from DR/INT to anti-PD-1 rechallenge was 233 days (range 3-1409). The ORR was 54%, CRR was 27%, and median PFS was 182 days (95%CI 127-357). There was no difference in PFS comparing BV and anti-PD-1 rechallenge (p=0.50) and no OS benefit of either BV or anti-PD-1 rechallenge, p=0.19 and 0.80 respectively. In 29 pts treated with alloSCT, the median time from DR/INT to alloSCT was 220 days (range 27-1971). AlloSCT was associated with longer OS compared to pts not treated with alloSCT (p<0.001), Figure 1. 3-year OS estimate was 96% (95%CI 75-99%) with alloSCT and 56% (95%CI 46-65%) without alloSCT. In 24 pts treated with CD30 directed CART, the median time from DR/INT to CART was 255 days (range 76-1600). CD30 directed CART was associated with longer OS compared to pts not treated with CART (p=0.009), Figure 2. 3-year OS estimate was 86% (95%CI 62-95%) with CART and 60% (95%CI 50-69%) without CAR-T. Only 2 pts were treated with both alloSCT and CART after DR/INT indicating that OS benefit was independent of cross over treatment. Conclusion: To our knowledge, this is the largest cohort analyzing treatment outcomes in pts refractory to, or intolerant of BV and anti-PD-1 therapy. Additionally, this study represents one of the largest evaluations of BV or anti-PD-1 rechallenge after prior DR or INT. BV and anti-PD-1 rechallenge were effective with high ORR, but median PFS with rechallenge was less than a year, indicating that rechallenge could be considered as a therapeutic bridge. There was no OS benefit of BV or anti-PD-1 rechallenge. AlloSCT and CD30 directed CART were highly effective and associated with longer OS. Pts with DR/INT cHL should be considered for alloSCT or CD30 directed CART.
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IJS, IMTLJ, KILJ, NLZOH, NUK, SAZU, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Brentuximab vedotin (BV) and anti-PD-1 therapies (nivolumab and pembrolizumab) have changed the therapeutic landscape for patients (pts) with classical Hodgkin lymphoma (cHL) over the ...past decade. Although first proven to be beneficial in relapsed and refractory cHL, these therapies have moved earlier in the treatment algorithm given superior response rates and survival compared to cytotoxic chemotherapy alone. However, there is limited data regarding outcomes in pts who progress after both BV and anti-PD-1 therapies (double refractory, DR) or become intolerant (INT) of these therapies. Knowledge of outcomes in this subset of pts is important as BV and anti-PD-1 therapies are increasingly used in front-line treatment and early relapsed cHL. Methods: We conducted a retrospective study of adult pts from 14 U.S. academic medical centers who developed DR cHL or became INT of BV and/or anti-PD-1 therapy between January 2011 and December 2021. DR was defined as treatment failure (evidence of progression by imaging or biopsy) during therapy or within 3 months of the last dose of both BV and anti-PD-1 therapy. INT was defined as any toxicity limiting further cycles of BV or anti-PD-1 therapy. Pts with INT were either intolerant to both BV and anti-PD-1 or intolerant and refractory to BV or anti-PD-1. The primary endpoint was assessment of overall survival from time of cHL diagnosis (OS-1) and from DR or INT (OS-2). Secondary endpoints included description of pt characteristics developing DR or INT cHL, estimate of OS comparing DR versus INT, and estimate of OS stratified by prior autologous stem cell transplant (ASCT) at the time of DR/INT. Time-to-event analyses were evaluated by Kaplan-Meier methodology. INT pts were not included in time to progression (TTP) analysis for initial BV or anti-PD-1 therapy. Results: 158 pts were eligible. Clinical characteristics at diagnosis included median age 33 years (range 16-89), 61% male, 77% white race, 66% nodular sclerosing subtype, 47% stage IV, and 56% with B symptoms. Front-line treatment was ABVD/AVD in 122 pts (77%) and BV or anti-PD-1 therapy in 28 pts (18%). 60% had primary refractory cHL (n=94). Table 1 describes pt characteristics in detail. Initial BV treatment was after a median of 2 lines of therapy (LOT) (range 0-7). The majority (60%, n=94) were treated with BV monotherapy and 15% (n=24) were treated with BV combined with anti-PD-1 therapy. Median TTP of BV refractory pts was 168 days (95%CI 138-190). Initial anti-PD-1 therapy was after a median of 3 LOT (range 0-12). Nivolumab was the most commonly used (72%) anti-PD-1 therapy. Median TTP of anti-PD-1 refractory pts was 223 days (95%CI 166-271). DR cHL was observed in 119 pts (75%), while 39 pts (25%) were INT. The median time from cHL diagnosis to DR/INT was 3.3 years (95%CI 0.5-23.1). At the time of DR/INT, 47% (n=75) had prior ASCT. The majority (87%, n=137) received subsequent LOTs after DR/INT (median 2, range 0-14). Table 1 describes DR/INT in detail. The median OS from the time of cHL diagnosis (OS-1) in all pts was 15.0 years (95%CI 9.4-20.9). There was no difference in OS-1 between DR and INT pts (log-rank p=0.83) or primary refractory and front-line relapsed pts (log-rank p=0.94). Pts who developed DR/INT at any time after ASCT had a significantly longer OS-1 compared to DR/INT without prior ASCT with a median OS of 19.1 years (95%CI 19.1-NR) versus 8.6 years (95%CI 5.3-15.0), respectively (log-rank p<0.001, Figure 1). Comparing pts with prior ASCT and no prior ASCT, the median age at DR/INT was 35 (range 20-75) versus 49 (range 18-90) years, Fisher's exact p=0.01. Adjusting for age at DR/INT did not impact the association between prior ASCT and improved OS, Cox proportional hazard ratio 0.48 (95%CI 0.25-0.90, p=0.02). Median OS from time of DR/INT (OS-2) was 7.4 years (95%CI 4.1-NR). OS-2 was not different between DR and INT pts (log-rank p=0.33). Conclusion: To our knowledge, this is the largest cohort of pts refractory to, or intolerant of BV and anti-PD-1 therapy. OS was longer than anticipated both from diagnosis and from time of DR/INT. Pts who were DR/INT after ASCT had a significantly longer OS. Further investigation is needed to determine if OS differences by ASCT may be due to disease biology or sequencing of therapies. Importantly, OS-2 serves as a benchmark for future clinical trials evaluating DR/INT cHL pts.
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IJS, IMTLJ, KILJ, NLZOH, NUK, SAZU, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Research indicates that Black cancer patients have higher rates of COVID-19 hospitalization than their White counterparts. However, the extent to which chronic diseases contribute ...to racial disparities remains uncertain. We aimed to quantify the effect of chronic diseases on racial disparity in COVID-19–associated hospitalization among cancer patients.
Methods
We linked Louisiana Tumor Registry’s data with statewide COVID-19 data and hospital in-patient discharge data to identify patients diagnosed with cancer in 2015-2019 who tested positive for COVID-19 in 2020 and those with COVID-19–associated hospitalization. Multivariable logistic regression and mediation methods based on linear structural equations were employed to assess the effects of the number of chronic diseases (0, 1-2, ≥3) and individual chronic diseases.
Results
Of 6381 cancer patients who tested positive for COVID-19, 31.6% were non-Hispanic Black cancer patients. Compared with non-Hispanic White cancer patients, non-Hispanic Black cancer patients had a higher prevalence of chronic diseases (79.5% vs 66.0%) and higher COVID-19–associated hospitalization (27.2% vs 17.2%). The odds of COVID-19–associated hospitalization were 80% higher for non-Hispanic Black cancer patients than non-Hispanic White cancer patients (odds ratio = 1.80, 95% confidence interval = 1.59 to 2.04). After adjusting for age, sex, insurance, poverty, obesity, and cancer type, number of chronic diseases explained 37.8% of the racial disparity in COVID-19–associated hospitalization, and hypertension, diabetes, and chronic renal disease were the top 3 chronic diseases explaining 9.6%, 8.9%, and 7.3% of the racial disparity, respectively.
Conclusion
Chronic diseases played a substantial role in the racial disparity in COVID-19–associated hospitalization among cancer patients, especially hypertension, diabetes, and renal disease. Understanding and addressing the root causes are crucial for targeted interventions, policies, and health-care strategies to reduce racial disparity.
e18790
Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes ...of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available; bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs IQR 46.5-63.25 vs 65 yrs IQR 55-74), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death; however, additional analyses, including multivariable regression, are warranted.
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