Clinical impact of transient lymphopenia.

Transient or persistent immunosuppression is a known risk factor for morbidity and mortality in critically ill patients. Aim of the present study is to evaluate the lymphopenia in patients admitted to the Emergency Unit of AOU Policlinico Umberto I, to investigate its prevalence at admission and the persistence during hospitalization until discharge. Possible correlations were evaluated between lymphopenia, diagnosis of admission, comorbidities and chronic treatments. In this study, 240 patients (142 men; 98 female; mean age 75.1 ± 15.1) were enrolled. Patients were divided into two groups according to the lymphocytes count at hospital admission, namely "Group A" with lymphopenia and "Group B" with values in the normal range. Moreover, the patients in group A were distinguished in relation to the regression or persistence of the lymphopenia assessed at the time of hospital discharge (Group A1: persistence; Group A2: normalization). Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; and none differences were observed regarding gender. Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; no differences were observed regarding gender. All subsets of the lymphocytes (CD4+, CD8+, NK) were equally reduced. Persistent lymphopenia was found in 19% of patients. Lymphopenia should be valued at the time of hospital admission as a factor influencing the prognosis, the management and the treatment of these patients.

Frequency of Dimethyl Fumarate-Induced Lymphopenia among Omani Patients with Multiple Sclerosis.

Objectives: Dimethyl fumarate (DMF) is known to cause lymphopenia when used to treat patients with multiple sclerosis (MS). However, research on DMF therapy in the Arab world, especially in Oman, is scarce. This study aimed to analyse the prevalence of lymphopenia among Omani patients with MS and their reasons for discontinuing DMF therapy. Methods: In this retrospective study, the medical records of Omani patients with MS who were treated using DMF at two tertiary hospitals in Muscat, Oman, from February 2017 to February 2023 were reviewed. Their demographic, clinical and laboratory data were retrieved and analysed. Absolute lymphocyte count values at baseline and at the last follow-up, as well as the reasons for discontinuing DMF therapy, were collected. Descriptive and inferential statistical techniques were used for data analysis. Binary-logistic regression analysis was used to identify the risk factors for DMF-induced lymphopenia. Results: A total of 64 Omani patients with MS were included in this study. The majority of the study participants (n = 40; 63%) were female. All included patients started DMF therapy at the mean age of 33 ± 7.7 years. After administration of DMF, 14 (21.9%) patients developed grades 1-3 of lymphopenia. The DMF therapy was discontinued for 23 (36.0%) patients, mainly in response to adverse events or confirmed pregnancy. Female gender was the only significant predictor of DMF-induced lymphopenia (P = 0.037). Conclusions: Most Omani patients with MS had mild lymphopenia (grades 1-2). Early adverse events and pregnancy were the main reasons provided for discontinuing DMF therapy.

Pooled prevalence of lymphopenia in all-cause hospitalisations and association with infection: a systematic review and meta-analysis.

BACKGROUND: Lymphopenia is defined as a decrease below normal value (often 1.0 x 109 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is associated with an increased risk of hospitalisation secondary to infection, independent of traditional clinical risk factors. In hospital, lymphopenia is associated with increased risk of healthcare-associated infection and mortality. By summarising lymphopenia's prevalence and impact on clinical outcomes, we can identify an at-risk population and inform future studies of immune dysfunction following severe illness. METHODS: Peer-reviewed search strategy was performed on three databases. Primary objective was to summarise the pooled prevalence of lymphopenia. Primary outcome was infection including pre-existing lymphopenia as a risk factor for admission with infection and as an in-hospital risk factor for healthcare-associated infection. Secondary outcomes were length of stay and mortality. Mortality data extracted included in-hospital, 28/30-day ('early'), and 90-day/1-year ('late') mortality. Meta-analysis was carried out using random-effects models for each outcome measure. Heterogeneity was assessed using I2 statistic. Joanna Briggs Institute checklist for cohort studies was used to assess risk of bias. The protocol was published on PROSPERO. RESULTS: Fifteen observational studies were included. The pooled prevalence of lymphopenia in all-cause hospitalisations was 38% (CI 0.34-0.42, I2= 97%, p< 0.01). Lymphopenia was not associated with an infection diagnosis at hospital admission and healthcare associated infection (RR 1.03; 95% CI 0.26-3.99, p=0.97, I2 = 55% and RR 1.31; 95% CI 0.78-2.20, p=0.31, I2=97%, respectively), but was associated with septic shock (RR 2.72; 95% CI 1.02-7.21, p=0.04, I2 =98%). Lymphopenia was associated with higher in-hospital mortality and higher 'early' mortality rates (RR 2.44; 95% CI 1.71-3.47, p < 0.00001, I2 = 89% and RR 2.05; 95% CI 1.64-2.56, p < 0.00001, I2 = 29%, respectively). Lymphopenia was associated with higher 'late' mortality (RR 1.59; 1.33-1.90, p < 0.00001, I2 = 0%). CONCLUSIONS: This meta-analysis demonstrates the high prevalence of lymphopenia across all-cause hospitalisations and associated increased risk of septic shock, early and late mortality. Lymphopenia is a readily available marker that may identify immune dysfunctional patients. Greater understanding of immune trajectories following survival may provide insights into longer-term poor clinical outcomes.

The comparison of COVID-19 vs seasonal influenza in children.

BACKGROUND: Influenza in children has been well described, whereas there has been a paucity of pediatric data regarding COVID-19. It is crucial for clinicians to differentiate cases of COVID-19 from cases of influenza because of the upcoming influenza season in the new pandemic era. METHODS: This retrospective study included pediatric patients who were diagnosed with laboratory-confirmed COVID-19 between March and September 2020, or seasonal influenza between October 2019 and March 2020. RESULTS: A total of 315 children were included in this study; 151 were diagnosed with influenza and 164 had confirmed COVID-19. The median age of patients with COVID-19 was 10 years (interquartile range [IQR]: 3-15 years), whereas the median age of patients with influenza was 4 years (IQR: 1-6 years) (p = 0.001). In the COVID-19 group, 6.3% of patients had underlying diseases, the most frequent being neurological conditions (3%). In the influenza group, 20.9% of patients had an underlying disease, the most frequent being asthma (14.5%). Fever (odds ratio [OR]: 20.476; 95% confidence interval [CI]: 2.438-171.995; p = 0.005), dyspnea/tachypnea (OR 13.950; 95% CI: 2.607-74.634; p = 0.002), and increased C-reactive protein (CRP) (OR: 7.650; 95% CI: 2.094-27.955; p = 0.002) were main predictors of influenza diagnosis in comparison to COVID-19. Lymphopenia was detected in 43.2% of patients with influenza and 19.9% of patients with COVID-19 (p = 0.001). CONCLUSIONS: The accurate differentiation between "influenza or COVID-19" seems possible by evaluating a combination of factors including cough, fever, vomiting, leucopenia, lymphopenia, pneumonia, in pediatric patients with high CRP as well as age.

Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD.

BACKGROUND AND OBJECTIVES: Ocrelizumab and rituximab are monoclonal antibodies targeting the CD20 marker on B lymphocytes. The enhanced efficacy of B lymphocyte depleting therapies poses a greater risk of decreased immunoglobulin (Ig) levels. The rate and risk factors of hypogammaglobulinemia in MS and NMOSD patients treated with anti-CD20 therapies are unknown. METHODS: A retrospective study was conducted among patients who received anti-CD20 therapy for the treatment of MS, NMOSD, and other related neurological disorders. The goal was to determine the incidence and risk factors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab versus rituximab. The secondary goals were to determine the rates of lymphopenia, neutropenia, and early B cell repopulation among patients on anti-CD20 therapy. RESULTS: Overall, 184 patients (mean age 48.4 ± 13.7, 66.8% female) met inclusion criteria; 152 patients received ocrelizumab and 32 patients received rituximab. A total of 22 patients (12%) developed hypogammaglobulinemia. Patients who developed hypogammaglobulinemia were more likely to have been ≥50 years of age (p = .0275) with lower baseline IgG (p = .001) and IgA (p = .0038) levels. Serious infections were observed in 21 patients (11%) and seen more commonly in those that developed total lymphopenia (<1.0 × 109/L) and had longer duration of B-cell therapy. Multivariate analysis identified age ≥ 50 years, white race, and rituximab as independent predictors of hypogammaglobulinemia, and absolute lymphopenia as an independent risk factor for serious infections. DISCUSSION: Among patients receiving anti-CD20 therapy, 12% of patients experienced hypogammaglobulinemia which was seen more commonly in white patients, at least 50 years old, with lower baseline IgG and IgA levels and in those treated with rituximab. Serious infections were seen more commonly in patients with total lymphopenia and longer exposure to anti-CD20 therapy.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients.

PURPOSE: One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation. MATERIALS AND METHODS: This is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression. RESULTS: Among the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01-1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86-0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05-40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29-53.20; p = 0.026). CONCLUSION: Patients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.

Predictors of hospitalization due to infection in rituximab-treated MS patients.

BACKGROUND: Rituximab is extensively used off-label to treat multiple sclerosis (MS), and long-term vigilance for adverse events is needed. This study was conducted to determine frequencies and predictors of hematological adverse events, including hypogammaglobulinemia, severe lymphopenia, neutropenia, and infections leading to hospitalization. METHODS: This retrospective cohort study included all patients with MS initiating rituximab treatment at Haukeland University Hospital between January 1st, 2017, and July 1st, 2021. Patients were followed by clinical monitoring and repeated blood sampling every six months. Clinical outcomes and laboratory results were retrieved from the Norwegian MS Registry and Biobank and the patient administrative system at Haukeland University Hospital. RESULTS: Five hundred and fifty-six patients were included, 515 with relapsing-remitting MS (RRMS) and 41 with progressive MS. Overall, 33 patients (5.9%) experienced 56 episodes of infections requiring hospital admission. Sixty patients (10.8%) had confirmed hypogammaglobulinemia, 17 (3.1%) had confirmed severe lymphopenia, and 10 (1.8%) had confirmed severe neutropenia. Predictors of infection requiring hospital admission were progressive MS (adjusted OR (aOR): 4.81; 95%CI: 1.25-18.48), duration of treatment with rituximab (aOR: 1.52; 95%CI: 1.11-2.09) and confirmed severe lymphopenia (aOR: 13.58; 95%CI: 3.41-54.06) and neutropenia (aOR: 13.40; 95%CI: 2.93-61.25). Of the hematological abnormalities, only hypogammaglobulinemia was associated with treatment duration (aOR: 1.35; 95%CI: 1.09-1.69). CONCLUSION: The risk of hospitalization due to infection is associated with time on rituximab treatment, in patients with lympho- or neutropenia, and in patients with primary progressive MS. We observed a time-dependent decline in IgG values, in contrast to neutrophil and lymphocyte count, suggesting a cumulative dose-dependent response. These predictors can assist clinicians in assessing and monitoring MS patients receiving rituximab.

The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.

BACKGROUND: Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia. OBJECTIVE: To determine if AE is associated with lymphopenia. METHODS: We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]). RESULTS: Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections. CONCLUSION: Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.

Clinical and serological factors associated with lupus pericarditis: a case-control study.

OBJECTIVE: Lupus pericarditis, a common manifestation of systemic lupus erythematosus (SLE), can be fatal. We examined the prevalence of lupus pericarditis and its associated factors in a Taiwanese SLE cohort. METHODS: Patients with SLE treated at Change Gung Memorial Hospital between January 2005 and December 2012 were included, and their age, sex, SLE disease duration, SLE disease activity index (SLEDAI) score, laboratory test results, comorbidities, and treatment regimen were noted. Factors related to lupus pericarditis were examined using univariate and multivariate logistic regression analyses. RESULTS: Of the 689 patients, 88.7% were women; age at diagnosis (± standard deviation (SD)) was 40.78 ± 15.59 years, and disease duration at study entry was 11.93 ± 8.21 years. The prevalence of lupus pericarditis was 16.4% (n = 113). Notably, older age at diagnosis (p = 0.0165), longer disease duration (p = 0.009), higher SLEDAI score (p < 0.0001), renal disorder (p = 0.003), lymphocytopenia (p < 0.0001), thrombocytopenia (p = 0.004), and anti-phospholipid antibody (aPL) seropositivity (p = 0.002) were significantly associated with lupus pericarditis. In multivariate analysis, adjusted for sex, SLE disease duration, age, and SLEDAI score, patients with lymphocytopenia and aPL seropositivity were related to a twofold (odds ratio (OR) 2.015, 95% confidence interval (CI) 1.091-3.858) and 1.5-fold (OR 1.569, 95% CI 1.017-2.421) greater prevalence of lupus pericarditis, respectively. CONCLUSIONS: Lupus pericarditis occurred in approximately one fifth of patients in this cohort. Patients with SLE with lymphocytopenia or anti-phospholipid antibody seropositivity were associated with a higher rate of lupus pericarditis. Key Points • Lupus pericarditis is a common manifestation of SLE that occurred in one-fifth patients in this study. • Lymphocytopenia and aPL antibody seropositivity are associated with a higher likelihood of developing lupus pericarditis. • Patients with lupus pericarditis should be identify early and treated with caution to prevent further morbidity and mortality.

Prevalence and outcome of lymphopenia in the Paediatric Intensive Care Unit: A prospective observational study.

AIM: Leukopenia (lymphopenia or neutropenia) may be an important marker of altered immunity and risk in children with critical illness. We aimed to evaluate the prevalence, course, and outcome of leukopenia in children admitted to Paediatric Intensive Care Unit (PICU). METHODS: All consecutive children (n = 200) admitted to PICU for any reason except malignancy or pre-existing immune deficiency were enrolled during June-August 2018. RESULTS: Median (interquartile range) age was 2.2 (0.6-8.5) years. About 52% (n = 103) had undergone a surgical procedure; 34% (n = 68) being cardiac surgery. Among medical illnesses, respiratory disorders were the most common (n = 39, 20%). Laboratory confirmed infections were present in 63 (31.5%) children. Leukopenia was identified in 135 (67.5%) children in the first week; 117 (58.5%) had only lymphopenia, 16 (8%) had both lymphopenia and neutropenia, and 2 (1%) had only neutropenia. In 69 children who had follow-up blood counts, lymphopenia resolved in 33 (48%) within 48 h and in another 20 (29%) by 4 days, and in a further 10 (14%) by 7 days. Children with lymphopenia had higher frequency of cardiac surgery, longer cardiopulmonary bypass time, greater need for invasive ventilation and vasopressor/inotrope therapy, and a higher probability of organ failure on day 4 and longer hospital stay. CONCLUSION: In critically ill children, lymphopenia is very common, often transient, but may be associated with unfavourable outcomes. Further studies with follow-up of blood counts in a larger sample are required to determine the course and outcomes of lymphopenia.

Severe Combined Immunodeficiency (SCID) Screening in Arizona: Lessons Learned from the First 2 Years.

PURPOSE: The incidence of severe combined immunodeficiency (SCID) in the USA was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of Native American and Hispanic populations compared to national percentages. The true incidence of SCID and non-SCID T cell lymphopenia has not previously been reported in Arizona. METHODS: A retrospective chart review was performed on all abnormal SCID newborn screening (NBS) tests in Arizona from January 1, 2018, to December 31, 2019, using data from the Arizona Department of Health Services and the Phoenix Children's Hospital's electronic medical record [IRB# 20-025]. RESULTS: Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis-type SCID. Thirteen infants were identified with an abnormal initial NBS which ultimately did not lead to a diagnosis of SCID. Four of these infants were diagnosed with congenital syndromes associated with T cell lymphopenia. Infants of Hispanic ethnicity were over-represented in this cohort. CONCLUSION: Over 2 years, NBS in Arizona confirmed an incidence more than 2.5 times that reported nationally. This increased incidence is likely reflective of Arizona's unique population profile, with a higher percentage of Native American population. The findings in our non-SCID cohort are in alignment with previously published data, except for an increased percentage of infants of Hispanic/Latino ethnicity, possibly reflecting Arizona's increased percentage of Hispanic/Latino population compared to the general US population.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

OBJECTIVES: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. RESULTS: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. CONCLUSIONS: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Lymphopenia during treatment with dimethyl fumarate in patients with multiple sclerosis: Prevalence, predicting factors and clinical outcomes.

BACKGROUND: Lymphopenia is a common side effect of treatment with dimethyl fumarate (DMF) in patients with multiple sclerosis (PwMS). Prevalence and predictive factors of this side effect are still uncertain, because literature has provided discrepant results and it is still a matter of debate if lymphopenia is associated with a better treatment outcome. METHODS: We retrospectively recruited PwMS treated for at least one month with DMF and collected clinical, demographic data and absolute lymphocyte count (ALC) during follow-up. Lymphopenia was graded according to CTCAE. Patients according to the grade in lymphopenia (all grades) and severe lymphopenia (grade II-IV). To evaluate predictors of lymphopenia, we compared characteristics of patients with/without lymphopenia and patients with/without severe lymphopenia. A logistic binary regression was performed to elucidate any predictive factor of lymphopenia and severe lymphopenia. Area under the curve (AUC) was calculated to evaluate sensibility and specificity of predictors. We analyzed treatment outcome with NEDA-3 status at 1- and 2-years. RESULTS: 98 of 105 patients treated with DMF were included. 46.9% developed lymphopenia, 27.6% severe lymphopenia. Lymphopenia was associated with basal ALC (p<0.001, AUC=0.786), treatment duration (p = 0.01, AUC=0.685),% of reduction at third month (p = 0.001, AUC=0.616) Severe lymphopenia was associated with basal ALC (p = 0.003, AUC=0.750).NEDA-3 status at 1-year (n = 66) and at 2-year (n = 44) did not differ in patients with/without lymphopenia (p = 0.059; p = 0.583) or with/without severe lymphopenia (p = 1.02; p = 0.169). CONCLUSION: Lymphopenia is a common side effect of DMF and basal ALC predicts its development. Lymphopenia is not associated with the achievement of NEDA-3 status.

Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate.

BACKGROUND: Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor-dependent and -independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results. OBJECTIVE: To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity. METHODS: A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020. RESULTS: Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036). CONCLUSION: Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.

Incidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate.

BACKGROUND: Dimethyl fumarate (DMF) is a disease modifying therapy (DMT) used in the management of Multiple Sclerosis (MS). Lymphopenia occurs in approximately 30% of people receiving this medication. The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication in the context of persistent lymphopenia, because of an increased risk of progressive multifocal leukoencephalopathy (PML). It is therefore important for clinicians and patients to be aware of the frequency of persistent, moderate-severe lymphopenia in order to make informed decisions regarding drug choice and safety monitoring. METHODS: We reviewed medical records of 156 people with MS (PwMS) started on DMF between 2014 and 2020, who received at least 6 months of treatment, in order to identify the incidence and duration of persistent lymphopenia. RESULT: Ten were excluded due to missing data. In 146 patients, treated for 30.7 months (mean), 16 (11%) were found to experience persistent moderate lymphopenia (0.5-0.7 × 109/L) and 5 (3%) experienced persistent severe lymphopenia (<0.5 × 109/L). Of the 5 patients with persistent severe lymphopenia, 3 discontinued DMF. Two cases stopped directly due to SPC recommendations and after 6-months no further DMTs were initiated. Treatment was withdrawn in a further case due to lack of efficacy. Two cases remained on DMF as their persistent severe lymphopenia predated SPC revision. Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respectively. Increased age was a predictor for persistent lymphopenia (B = 0.071, p = 0.004) while sex, and previous DMT were not.

Chemotherapy is a risk factor of lymphopenia before adjuvant radiotherapy in breast cancer.

BACKGROUND: Lymphopenia can decrease immune function of the host and is a known risk factor for poor prognosis in malignant tumors. Radiation induced lymphopenia was common in patients with breast cancer and was also reported to have a negative effect on long-term outcome. AIMS: Lymphopenia may be associated with baseline immune status before radiotherapy (RT). This study aimed to explore the rate and risk factors of lymphopenia before start of the adjuvant RT in patients with breast cancer. METHODS: Patients with invasive breast cancer treated from March 2015 to February 2020 and with peripheral lymphocyte counts (PLC) available within 7 days from the beginning of RT were eligible for this study. Data were presented as mean and 95% confidence interval unless otherwise specified. The risk factors of low PLC before RT were identified using univariate and multivariable linear regressions. RESULTS: A total of 1012 consecutive patients met the study criteria. The mean PLC before RT commencement was 1.58*109 /L (95%CI: 1.55-1.62*109 /L) with 15.2% (95%CI: 13.1%-17.6%) CTCAE defined lymphopenia, rendering 12.3%, 2.6%, 0.3%, and 0% for grade 1, 2, 3 and 4 respectively. Univariate and multivariable linear regression showed prior chemotherapy was the most significant risk factor (p < .001) for low PLC, while age, menopausal status and lymph node stage were not (all ps > .05). A total of 912 (90.1%, 95%CI: 88.1%-91.9%) patients had chemotherapy before adjuvant RT in this study. In patients with HR+/HER2- breast cancer, 69.0% (95%CI: 63.0%-74.5%) N0 and 98.1% (95%CI: 95.1%-99.5%) N1 had also received chemotherapy. CONCLUSIONS: Patients with breast cancer might have lymphopenia from prior chemotherapy at the start of adjuvant RT which could have negative effect on long-term outcome. It is also noted that most of the patients with HR+/HER2-, early-stage breast cancer were treated with aggressive chemotherapy without knowing the risk of chemotherapy induced lymphopenia. Future study on predictive or prognostic multigene assays is warranted to avoid unnecessary chemotherapy and subsequent lymphopenia in patients with low risk breast cancer.

Nutritional status in patients with COVID-19 and cancer: the experience of the National Cancer Institute in Mexico / Estado nutricional en pacientes con COVID-19 y cáncer: la experiencia del Instituto Nacional de Cancerología de México

Background: nutritional status might vary according to different underlying illnesses such as cancer or infectious diseases, including COVID-19. In this context, data from developing countries remain scarce. Objectives: the objective of this study was to assess the nutritional status and outcomes of Mexican cancer patients diagnosed with COVID-19 at a tertiary care center. Methods: this was a retrospective study including 121 consecutive cancer patients diagnosed with COVID-19 at the National Cancer Institute, Mexico City, during four months. Results: the most frequent oncological diagnoses were gynecological (19 %) and hematological (17 %). Most patients were overweight (35 %). In the univariate analysis, ≥ 65 years, intubation, hypoalbuminemia, high creatinine, lymphopenia, nutrition-impact symptoms, and ECOG 2-4 were statistically associated with lower survival. The median survival of the cohort was 41 days. Conclusions: to our best knowledge, this is the first study of its kind performed in Mexico, and as other studies from other regions, our results might aid in identifying cancer patients most at risk for severe COVID-19, and could be potentially useful to enhance public health messaging on self-isolation and social distancing among Mexican cancer patients. (AU)

Antecedentes: el estado nutricional puede variar según las diferentes enfermedades subyacentes, como el cáncer o las enfermedades infecciosas, por ejemplo, la COVID-19. En este contexto, los datos de los países en desarrollo siguen siendo escasos. Objetivos: el objetivo de este estudio fue evaluar el estado nutricional y los resultados de pacientes mexicanos con cáncer diagnosticados de COVID-19 en un centro de atención terciaria. Métodos: se trata de un estudio retrospectivo que incluyó a 121 pacientes consecutivos con cáncer diagnosticados de COVID-19 en el Instituto Nacional del Cáncer de la Ciudad de México durante cuatro meses. Resultados: los diagnósticos oncológicos más frecuentes fueron los ginecológicos (19 %) y hematológicos (17 %). La mayoría de los pacientes tenían sobrepeso (35 %) y obesidad (31 %). En el análisis univariado, ≥ 65 años, intubación, hipoalbuminemia, creatinina alta, linfopenia, síntomas de impacto nutricional y ECOG 2-4 se asociaron estadísticamente con una menor supervivencia. La mediana de supervivencia de la cohorte fue de 41 días. Conclusiones: hasta donde sabemos, este es el primer estudio de este tipo realizado en México y, al igual que otros estudios de otras regiones, nuestros resultados podrían ayudar a identificar a los pacientes con cáncer y mayor riesgo de COVID-19 grave; también podrían ser potencialmente útiles para mejorar los mensajes de salud sobre el autoaislamiento y el distanciamiento social entre los pacientes mexicanos con cáncer. (AU)

Identifying Individualized Risk Profiles for Radiotherapy-Induced Lymphopenia Among Patients With Esophageal Cancer Using Machine Learning.

PURPOSE: Radiotherapy (RT)-induced lymphopenia (RIL) is commonly associated with adverse clinical outcomes in patients with cancer. Using machine learning techniques, a retrospective study was conducted for patients with esophageal cancer treated with proton and photon therapies to characterize the principal pretreatment clinical and radiation dosimetric risk factors of grade 4 RIL (G4RIL) as well as to establish G4RIL risk profiles. METHODS: A single-institution retrospective data of 746 patients with esophageal cancer treated with photons (n = 500) and protons (n = 246) was reviewed. The primary end point of our study was G4RIL. Clustering techniques were applied to identify patient subpopulations with similar pretreatment clinical and radiation dosimetric characteristics. XGBoost was built on a training set (n = 499) to predict G4RIL risks. Predictive performance was assessed on the remaining n = 247 patients. SHapley Additive exPlanations were used to rank the importance of individual predictors. Counterfactual analyses compared patients' risk profiles assuming that they had switched modalities. RESULTS: Baseline absolute lymphocyte count and volumes of lung and spleen receiving ≥ 15 and ≥ 5 Gy, respectively, were the most important G4RIL risk determinants. The model achieved sensitivitytesting-set 0.798 and specificitytesting-set 0.667 with an area under the receiver operating characteristics curve (AUCtesting-set) of 0.783. The G4RIL risk for an average patient receiving protons increased by 19% had the patient switched to photons. Reductions in G4RIL risk were maximized with proton therapy for patients with older age, lower baseline absolute lymphocyte count, and higher lung and heart dose. CONCLUSION: G4RIL risk varies for individual patients with esophageal cancer and is modulated by radiotherapy dosimetric parameters. The framework for machine learning presented can be applied broadly to study risk determinants of other adverse events, providing the basis for adapting treatment strategies for mitigation.

Nutritional status in patients with COVID-19 and cancer: the experience of the National Cancer Institute in Mexico.

INTRODUCTION: Background: nutritional status might vary according to different underlying illnesses such as cancer or infectious diseases, including COVID-19. In this context, data from developing countries remain scarce. Objectives: the objective of this study was to assess the nutritional status and outcomes of Mexican cancer patients diagnosed with COVID-19 at a tertiary care center. Methods: this was a retrospective study including 121 consecutive cancer patients diagnosed with COVID-19 at the National Cancer Institute, Mexico City, during four months. Results: the most frequent oncological diagnoses were gynecological (19 %) and hematological (17 %). Most patients were overweight (35 %). In the univariate analysis, ≥ 65 years, intubation, hypoalbuminemia, high creatinine, lymphopenia, nutrition-impact symptoms, and ECOG 2-4 were statistically associated with lower survival. The median survival of the cohort was 41 days. Conclusions: to our best knowledge, this is the first study of its kind performed in Mexico, and as other studies from other regions, our results might aid in identifying cancer patients most at risk for severe COVID-19, and could be potentially useful to enhance public health messaging on self-isolation and social distancing among Mexican cancer patients.

INTRODUCCIÓN: Antecedentes: el estado nutricional puede variar según las diferentes enfermedades subyacentes, como el cáncer o las enfermedades infecciosas, por ejemplo, la COVID-19. En este contexto, los datos de los países en desarrollo siguen siendo escasos. Objetivos: el objetivo de este estudio fue evaluar el estado nutricional y los resultados de pacientes mexicanos con cáncer diagnosticados de COVID-19 en un centro de atención terciaria. Métodos: se trata de un estudio retrospectivo que incluyó a 121 pacientes consecutivos con cáncer diagnosticados de COVID-19 en el Instituto Nacional del Cáncer de la Ciudad de México durante cuatro meses. Resultados: los diagnósticos oncológicos más frecuentes fueron los ginecológicos (19 %) y hematológicos (17 %). La mayoría de los pacientes tenían sobrepeso (35 %) y obesidad (31 %). En el análisis univariado, ≥ 65 años, intubación, hipoalbuminemia, creatinina alta, linfopenia, síntomas de impacto nutricional y ECOG 2-4 se asociaron estadísticamente con una menor supervivencia. La mediana de supervivencia de la cohorte fue de 41 días. Conclusiones: hasta donde sabemos, este es el primer estudio de este tipo realizado en México y, al igual que otros estudios de otras regiones, nuestros resultados podrían ayudar a identificar a los pacientes con cáncer y mayor riesgo de COVID-19 grave; también podrían ser potencialmente útiles para mejorar los mensajes de salud sobre el autoaislamiento y el distanciamiento social entre los pacientes mexicanos con cáncer.

Admission Lymphocytopenia is Associated with Urinary Tract Infection and Nosocomial Infections in Hemorrhagic Stroke.

OBJECTIVE: Growing evidence suggests that lymphocytopenia on admission (LOA) is associated with infectious complications and poor outcomes in intracerebral hemorrhage (ICH). Whether LOA preferentially increases the risk for community acquired infections or nosocomial infections is unknown. This study investigates the relationship between LOA and nosocomial infections in a cohort of patients with ICH in a safety-net hospital. MATERIAL AND METHODS: This is a single center, observational, retrospective study of 213 patients with non-traumatic ICH admitted to the neurocritical care unit between 2008 and 2014. Patients' clinical, demographic, lab and radiologic data were retrieved from institutional electronic medical records. Nosocomial infection was defined as clinical onset 48 h after admission. RESULTS: Prevalence of LOA was 24.8%. Patients with LOA showed significant associations with mechanical ventilation (67.9% versus 49.4%; p= 0.019), higher median ICH score (2 versus 1; p=0.006), nosocomial infection (43.4% versus 28.0%; p=0.038), nosocomial UTI (24.5% versus 8.9%; p=0.003). Adjusting for baseline covariates in a multivariate logistic regression, we observed an association of LOA with nosocomial UTI (OR, 3.66 [95% CI, 1.36-9.88], p=0.010). From the Cox proportional model, patients with LOA had 1.76 times the hazard of developing of nosocomial infection, compared to those without LOA ([95% CI: 1.01, 3.07], p=0.046) and had 3.27 times the hazard of developing nosocomial UTI, compared to those without LOA ([95% CI: 1.39, 7.67], p=0.007). CONCLUSIONS: This study is the first to show that LOA is associated with nosocomial urinary tract infections and significantly shorter times to develop nosocomial infections.