Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma

Purpose Lymphopenia is frequently observed and is associated with poor prognosis in glioblastoma (GBM) patients. Restoring lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin-7 (IL-7) is necessary for proliferation of lymphocytes and to amplify the total lymphocyte count (TLC), IL-7 therapy has been tried for various cancers, although the results are inconclusive. Here, we describe the clinical results of recurrent GBM treated with long-acting engineered version of recombinant human IL-7 (rhIL-7-hyFc). Methods This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Patients with recurrent GBM were enrolled to Seoul St. Mary's Hospital. Primary outcomes were the safety profile and elevated total lymphocyte count (TLC). Secondary outcomes were overall survival (OS) and progressionbfree survival (PFS). The duration of median follow up was 372.6 days (range 98-864 days). Results Among 18 patients enrolled, 10 received rhIL-7-hyFc with temozolomide, 5 received rhIL-7-hyFc with bevacizumab, 1 received rhIL-7-hyFc with PCV chemotherapy, and 2 received rhIL-7-hyFc alone. The mean TLC of enrolled patients after the first treatment with rhIL-7-hyFc was significantly increased from 1,131 cells/mm^3 (range 330-2,989) at baseline to 4,356 cells/mm^3 (range 661-22,661). Similar increase was observed in 16 of 18 patients (88.8%), only after the first treatment of rhIL-7-hyFc. TLCs of these patients were maintained higher while rhIL-7-hyFc was repeatedly administered. Most common adverse events were injection sites reactions (64.7%) including urticaria and itching sensation, however, there were no serious adverse events more than grade III. Median OS and PFS were 378 days (range 107-864 days) and 231 days (55-726 days), respectively. Conclusion Our study first reports that IL-7 immunotherapy can restore lymphopenia and maintain TLC with various salvageable chemotherapies in recurrent GBM patients without serious adverse toxicities. This outcome warrants further larger and randomized clinical trials to validate the clinical benefits of rhIL-7-hyFc for GBM patients.

Malnutrition Contributes to Low Lymphocyte Count in Early-Stage Coronavirus Disease-2019

Background and Aim: Lymphocytes play an important role in fighting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Low total lymphocyte count (TLC), which contributes to poor clinical outcomes, is common in persons with coronavirus disease 2019 (COVID-19). The current explanation for the cause of low TLC is that it is directly related to the invasiveness of SARS-CoV-2, which attacks lymphocytes. We hypothesized that malnutrition contributes to the development of low TLC in early-stage COVID-19.Methods: We prospectively enrolled 101 patients with confirmed COVID-19. On their first day of hospitalization, we collected baseline and laboratory data, including clinical symptoms; the Sequential Organ Failure Assessment, Nutrition Risk Screening 2002 and Subjective Global Assessment were used to assess the malnutrition status of the patients. Multivariable logistic regression was used to identify independent risk factors for low TLC and severe COVID-19.Results: Malnutrition was associated with lower TLC in COVID-19. Fifty-nine (58.4%) of the patients showed low TLC, 41 (40.6%) were at risk for malnutrition, and 18 of them were malnourished. Low TLC was an independent risk factor for severe COVID-19. Compared to patients with normal TLC, those with low TLC more often presented with anorexia, malnutrition, higher SOFA scores (P < 0.05) and comorbidities (diabetes and malignancies). Malnutrition (OR: 3.05, 95% CI: 1.5–6.19, P = 0.006) and SOFA scores (OR: 1.51, 95% CI: 1.04-2.43, P = 0.042) were identified as independent risk factors for low TLC.Conclusions: Malnutrition was common among our patients with early-stage COVID-19, and it contributed to the occurrence of low TLC.

Distinct Clinical and Laboratory Patterns of Pneumocystis jirovecii Pneumonia in Renal Transplant Recipients

Late post-transplant Pneumocystis jirovecii pneumonia (PcP) has been reported in many renal transplant recipients (RTRs) centers using universal prophylaxis. Specific features of PcP compared to other respiratory infections in the same population are not well reported. We analyzed clinical, laboratory, administrative and radiological data of all confirmed PcP cases between January 2009 and December 2014. To identify factors specifically associated with PcP, we compared clinical and laboratory data of RTRs with non-PcP. Over the study period, 36 cases of PcP were identified. Respiratory distress was more frequent in PcP compared to non-PcP (tachypnea: 59%, 20/34 vs. 25%, 13/53, p = 0.0014; dyspnea: 70%, 23/33 vs. 44%, 24/55, p = 0.0181). In contrast, fever was less frequent in PcP compared to non-PcP pneumonia (35%, 11/31 vs. 76%, 42/55, p = 0.0002). In both cohorts, total lymphocyte count and serum sodium decreased, whereas lactate dehydrogenase (LDH) increased at diagnosis. Serum calcium increased in PcP and decreased in non-PcP. In most PcP cases (58%, 21/36), no formal indication for restart of PcP prophylaxis could be identified. Potential transmission encounters, suggestive of interhuman transmission, were found in 14/36, 39% of patients. Interhuman transmission seems to contribute importantly to PcP among RTRs. Hypercalcemia, but not elevated LDH, was associated with PcP when compared to non-PcP.

Effect of N-Acetylcysteine on IL-10 and Total Lymphocyte Count in HIV Infected Patients Undergoing Antiretroviral Treatment

Objective: To determine NAC oral administration’s effect on changes in IL-10 levels and total lymphocyte count (TLC) in patients with HIV/AIDS in Dr Mohammad Hoesin Hospital, Palembang. Material and Methods: This study was a double-blind, randomized clinical trial. A total of 32 HIV/AIDS patients undergoing ARV treatment were randomly divided into two groups: the placebo and NAC groups. In the placebo group, patients were given capsules containing lactose at a dose of 3x1 capsules/ day, while the NAC group, were given NAC at a dose of 3x200 mg/day. Each group was treated for 12 weeks. Results: NAC administration significantly reduced IL-10 levels P= 0.038 but could not significantly increase TLC after treatment P= 0.376. However, TLC on the NAC group remained higher when compared with TLC on the placebo group. Conclusion: NAC administration significantly reduced levels of IL-10 and increased TLC; therefore, NAC has potential effects of increasing the effectiveness of antiretroviral therapy in HIV/AIDS patients, although it still needs to be studied further. J MEDICINE 2021; 22: 114-118

Correlation between Ascites and Total Lymphocyte Count with Occurrence of Hepatic Encephalopathy in Liver Cirrhosis Patients

Hepatic encephalopathy (HE) is brain dysfunction manifested as a broad spectrum of neuropsychiatric abnormalities caused by hepatic insufficiency or portosystemic shunting due to portal hypertension. Portal hypertension in liver cirrhosis also causes ascites, as the most common clinical manifestation. Further, immune dysfunction, one of which is decreased total lymphocyte count (TLC), happens at liver cirrhosis, which triggers the systemic inflammatory response. This systemic inflammatory response plays a role in HE. Objective of this study is to know the correlation between ascites and TLC with occurence of HE in liver cirrhosis patient. This study was conducted by retrospective cohort design in Saiful Anwar Hospital. Determination of sample amount at this study used total sampling method. Hepatic encephalopathy diagnosis was based on West Haven Criteria. Ascites was determined by physical examination and/or abdominal ultasonography. Total lymphocyte count data was taken from medical record, with complete blood count examination used XS-800i hematology analyzer machine. Data were analyzed using a logistic regression test, with p&lt;0.05 was considered significant and Confidence Interval (CI) 95%. Seventy-eight liver cirrhosis patients were observed using a retrospective cohort method regarding the HE occurrence, and physical examination for ascites and laboratory examination were performed. The statistical analysis result of the correlation between ascites and HE is significant with an odds ratio of 5.108 and CI of 1.36-19.25. On the other hand, TLC has no significant correlation with the occurrence of HE. Based on this analysis result, it is concluded that ascites has a correlation with HE, but TLC does not.<p> </p>

Low Total Lymphocyte Count as the Risk of Hospital Acquired Malnutrition in Children

Background: Hospital Acquired Malnutrition (HAM) is characterized by inadequate nutritional therapy and the risk of developing malnutrition during the hospital stay. In clinical practice, there are many measurements to determine nutritional status. Total lymphocyte count (TLC) is associated with impaired function of immune system in malnutrition. The purpose of this study was to evaluate the prognostic value of TLC to the occurrence of HAM in pediatric patients.Materials and Methods: This an observational study with a prospective cohort design. Subjects were assessed for weight at the first day of hospitalization, then the subjects were followed until they were discharged. Body weight was re-measured on discharge to determine the presence or absence of HAM. This research was conducted at Sanglah Hospital from May-December 2019. Subjects who met the inclusion and exclusion criteria were enrolled in the study.Results: Among 120 subjects, 55 subjects or 45.8% were malnourished on admission. Subjects with a low TLC compared to a normal TLC had a 3.9-fold risk of experiencing hospital acquired malnutrition (95% Confidence Interval: 1.59 to 7.19, p=0.001). Subjects who had a low TLC had HAM of 61.8%, while subjects who had a normal TLC had HAM of 32.3%. In multivariate analysis, low TLC was the only risk factor for HAM in this research.Conclusion: This study proved that low TLC is the risk of HAM. Total lymphocyte count could be used as predictor of the risk of HAM in hospitalization children.Keywords: hospital malnutrition, total lymphocyte, children

Determination of lymphocyte subgroups and activation status of them with flow cytometry at the time of diagnosis in COVID-19 patients

Background: Although changes of the main lymphocyte subsets (T cells, T helper, T cytotoxic, B cells, NK cells) and lymhocyte activation status in COVID-19 patients have been reported, the results of the studies differ each other. Therefore, we aimed to determine lymphocyte subgroups and activation status of them with flow cytometry at the time of diagnosis in COVID-19 patients and examine the relation of them with disease stage and length of hospital stay. Methods: Fourty patients included in the study were compared with the age and sex matched 40 healthy controls. COVID-19 patients were divided into 2 groups as mild and severe stage disease. Flow cytometry assay was performed to examine the numbers of lymphocyte subsets and activation status of them. Total lymphocyte count was calculated and CD45, CD3, CD4, CD8, CD19, CD27, CD38, CD56, CD57, IgD were studied on lymphocyte gate. T helper / T cytotoxic rates and length of hospital stay were recorded. Results: The patients’ CD3(+)CD4(+) ( T helper) count and CD27 expression on T cells counts were significantly lower, and CD57 expression on CD3(+)CD8(+) T cytotoxic cells were significantly higher (p<0.05) than control gruop. When the patients were divided into mild and severe stages, it was observed that CD38 expression on T cells were significantly lower in severe stage patients (p< 0.05) Total lymphocyte count and CD3(+) T lymphocyte count were negatively correlated with the lengt of hospital stay as statistically significant (p <0.05). Conclusion: Our data showed that the SARS-CoV-2 primarly effects on T lymphocytes. It was thought that this effect occured by impairment of development and activation of T lymphocytes. There are some discordances among the studies on T lympocytes in the literature. Studies with more patients are needed to make this information more reliable.

Medical Nutrition Therapy in Ascendens Colon Perforation Due to Intestinal Tuberculosis With Severe Malnutrition: A Case Report

Objectives Intestinal tuberculosis (TB) cases increased with the increase in TB cases in general. Intestinal TB was found in 11% of extrapulmonary TB patients. Severe malnutrition was associated with poor outcome in TB patients. Due to inflammation process, TB patients were in hypermetabolic conditions which caused increase in nutritional requirements. Intestinal TB with severe malnutrition need spesific nutritional therapy, tailored to each patient based on their nutritional status and clinical condition. Methods A 41-year old male patient with severe malnutrition (body mass index 17,9 kg/m2) diagnosed with post laparotomy due to perforation of ascending colon due to Intestinal TB. Oral intake decreased due to loss of appetite and abdominal pain. Patient showed pale in conjunctival, loss of subcutaneous fat, wasting and edema in extremities. Laboratory findings were anemia (7.5 g/dL), hypoalbuminemia (2.4 g/dL), hyponatremia (130 mmol/L), hypokalemia (3.0 mmol/L) and severe depletion of total lymphocyte count (477/mL). Patient suffered from post-operative complications in the form of post-operative ileus, low output enterocutaneous fistula and suspected an anastomoses leakage. Results Medical nutrition therapy was given with a total calorie of 1175 kcal and increased gradually to 2000 kcal, protein 0.8–2 g/Ideal Body Weight/day using high protein formula and amino acids parenteral nutrition, including glutamine infussion. We administered suplementations which were zinc, multivitamins, curcuma and snakehead fish extract. Patient was discharged after 37 days with clinical and functional capacity improvement assessed with handgrip dynamometer from 11.2 to 23.4 kg. Laboratory improvement were Hemoglobin 10.1 g/dL, Albumin 2.8 mg/dL, Sodium 143 mmol/L, Potassium 4.2 mmol/L and Total lymphocyte count 904/mL. Post-operative complications were improved. Conclusions Malnourished patient with intestinal TB who undergoing surgery had an increased risk of nutritional deficiencies and postoperative complications. Specific nutritional therapy to reduce inflammation or hypermetabolic, and to treat post surgical complications, proper monitoring and nutritional education results in a good outcome for patient. Funding Sources The author(s) received no financial support for the research, autorship and/or publication of this article.