Effect of Cumulative Dexamethasone Dose during Concomitant Chemoradiation on Lymphopenia in Patients with Newly Diagnosed Glioblastoma

( Changik Lee ),( Stephen Ahn ),( Jae-sung Park ),( Jin Ho Song ),( Yong-kil Hong ),( Sin-soo Jeun ) 대한뇌종양학회 대한신경종양학회 2020 Brain Tumor Research and Treatment Vol.8 No.2

Background Lymphopenia frequently occurs after concomitant chemoradiation (CCRT) in patients with glioblastoma (GBM) and is associated with worse overall survival (OS). A few studies have tried to identify risk factors for lymphopenia; however, the results were not clear. We aimed to identify potential risk factors for lymphopenia, focusing on the use of dexamethasone to control cerebral edema in patients with GBM. Methods The electronic medical records of 186 patients with newly diagnosed GBM treated at our institution between 2009 and 2017 were retrospectively examined. Acute lymphopenia was defined as total lymphocyte count less than 1,000 cells/μL at 4 weeks after completion of CCRT. Multivariate logistic regression analysis was used to identify independent risk factors for lymphopenia, and Cox regression analysis was used to identify independent risk factors for OS. Results Of the 125 eligible patients, 40 patients (32.0%) developed acute lymphopenia. Female sex and median daily dexamethasone dose ≥2 mg after initiation of CCRT were independent risk factors for acute lymphopenia on multivariate analysis. Acute lymphopenia, extent of surgical resection, and performance status were associated with OS; however, dexamethasone use itself was not an independent risk factor for poor OS. Conclusion Female sex, median daily dexamethasone dose ≥2 mg after initiation of CCRT until 4 weeks after completion of CCRT may be associated with acute lymphopenia. However, dexamethasone use itself did not affect OS in patients newly diagnosed with GBM. These results should be validated by further prospective studies controlling for other confounding factors.

Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation

Joshua T. Cohen,Kevin P. Charpentier,Thomas J. Miner,William G. Cioffi,Rachel E. Beard 한국간담췌외과학회 2021 Annals of hepato-biliary-pancreatic surgery Vol.25 No.2

Backgrounds/Aims: Post-operative pancreatic fistulas (POPF) are a major source of morbidity following pancreaticoduodenectomy (PD). This study aims to investigate if persistent lymphopenia, a known marker of sepsis, can act as an additional marker of POPF with clinical implications that could help direct drain management. Methods: A retrospective chart review of all patients who underwent PD in a single hospital network from 2008 to 2018. Persistent lymphopenia was defined as lymphopenia beyond post-operative day #3. Results: Of the 201 patients who underwent PD during the study period 161 patients had relevant laboratory data, 81 of whom had persistent lymphopenia. 17 patients with persistent lymphopenia went on to develop a POPF, compared to 7 patients without. Persistent lymphopenia had a negative predictive value of 91.3%. Multivariate analysis revealed only persistent lymphopenia as being independently associated with POPF (HR 2.57, 95% CI 1.07-6.643, p=0.039). Patients with persistent lymphopenia were more likely to have a complication requiring intervention (56.8% vs 35.0%, p<0.001). Conclusions: Persistent lymphopenia is a readily available early marker of POPF that holds the potential to identify clinically relevant POPF in patients where no surgical drain is present, and to act as an adjunct of drain amylase helping to guide drain management.

The Association of Lymphopenia with the Clinical Severity in the Korean Children Admitted to the Hospital with Pandemic (H1N1) 2009 Infection

전진경,김황민,차병호,어영,김효열,김영근,권우철 대한감염학회 2011 Infection and Chemotherapy Vol.43 No.1

Background: Critical illness due to pandemic (H1N1) 2009 is an emerging threat to global health. In this study, lymphopenia was focused on as a major risk factor for a critical clinical course of pandemic (H1N1) 2009 infection. We investigated the association of lymphopenia at the time of admission with the clinical severity of the admitted children with pandemic (H1N1) 2009 infection. Material and Methods: We performed a retrospective study on the patients who were younger than 15 years of age and who were admitted to Wonju Christian Hospital due to pandemic (H1N1) 2009 infection between August 20, 2009 and February 20, 2010. Pandemic (H1N1) 2009 infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) in all patients. We divided the study period into two periods as August 20 -November 30 2009 (pre-vaccination period) and December 1 2009- February 20 2010 (post-vaccination period). The clinical differences between two periods were analyzed. To define the role of lymphopenia, we examined the differences of clinical manifestations between the H1N1 patients with lymphopenia and those without lymphopenia. Results: Among the 2,399 children who had H1N1 infection, 149 patients (6.2%)were admitted under the following diagnoses: pneumonia (67.1%), bronchiolitis/asthma (18.8%), croup (6%) and febrile convulsion (8.7%). The median age of the patients was significantly different between during the pre-vaccination period and the post-vaccination period (6 years of age [range: 0.25-14] vs. 3 years of age, [range:0.1-14], P<0.05). The proportion of patients who had lymphopenia was significantly different between two periods (39.5% vs. 20%, P<0.05). When we compared the clinical severity between the patients with lymphopenia and those without lymphopenia, age (P<0.0001), the length of hospital stay (P<0.0001) and the serum levels of C-reactive protein (P<0.01) were significantly different. Conclusion: Our data support that lymphopenia may be a major determining factor that could cause a critical clinical course during pandemic period among children in the Republic of Korea.

Safety and Temporal Pattern of the Lymphocyte Count During Fingolimod Therapy in Patients With Multiple Sclerosis: Real-World Korean Experience

So-Young Huh,Su-Hyun Kim,Ki Hoon Kim,Young Nam Kwon,Sung-Min Kim,Seung Woo Kim,Ha Young Shin,Yeon Hak Chung,Ju-Hong Min,Jungmin So,Young-Min Lim,Kwang-Kuk Kim,Nam-Hee Kim,Tai-Seung Nam,Sa-Yoon Kang,Je 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.6

Background and Purpose Fingolimod (FTY) inhibits lymphocyte egress from lymphoid organs to cause lymphopenia, but the clinical implications of FTY-induced lymphopenia are not fully understood. We aimed to determine the frequency and severity of lymphopenia during FTY treatment among Korean patients with multiple sclerosis (MS), and its association with infections. Methods We retrospectively reviewed the medical records of patients with MS treated using FTY from 12 referral centers in South Korea between March 2013 and June 2021. Patients were classified according to their nadir absolute lymphocyte count (ALC) during treatment: grade 1, 800–999/μL; grade 2, 500–799/μL; grade 3, 200–499/μL; and grade 4, <200/μL. Results FTY treatment was administered to 69 patients with a median duration of 18 months (range=1–169 months), with 11 patients being treated for ≥7 years. During FTY treatment, mean ALCs were reduced after the first month (653.0±268.9/μL, mean±standard deviation) (p<0.0001) and remained low during treatment lasting up to 84 months. During follow-up, 41 (59.4%) and 7 (10.1%) patients developed grade-3 and grade-4 lymphopenia, respectively. No significant difference was found in age at FTY initiation, sex, baseline ALC, body mass index, or prior disease-modifying treatment between patients with and without grade-4 lymphopenia. Infections were observed in 11 (15.9%) patients, and the frequencies of patients with and without grade-4 lymphopenia were similar. Conclusions FTY treatment induced grade-4 lymphopenia in 10% of South Korean patients with MS, but did not appear to be associated with an increased infection risk.

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort

변화경,정승연,김경진,성진실 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia. Materials and Methods A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively. Results Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months. Conclusion IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-Hoc Analysis of a Prospective Cohort

( Hwa Kyung Byun ),( Seung Yeun Chung ),( Kyoung-jin Kim ),( Jinsil Seong ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients

Li-Ting Liu,Qiu-Yan Chen,Lin-Quan Tang,Shan-Shan Guo,Ling Guo,Hao-Yuan Mo,Ming-Yuan Chen,Chong Zhao,Xiang Guo,Chao-Nan Qian,Mu-Sheng Zeng,Jin-Xin Bei,Jing Tan,Shuai Chen,Ming-Huang Hong,Jian-Yong Shao 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1

Purpose This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC). Materials and Methods A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. Results A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ! 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ! 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ! 390 cells/μL and post3m-ALC ! 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006). Conclusion Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

폐암환자에서 종격동 방사선조사 후에 발생하는 림프구 감소증

오윤경(Yoon Kyeong Oh),하철수(Chul Soo Ha),박희철(Hee Chul Park),이승일(Seung Il Lee),류소연(So Yeon Ryu),기근홍(Keun Hong Kee),전호종(Ho Jong Jeon) 대한방사선종양학회 2002 Radiation Oncology Journal Vol.20 No.1

목적: 방사선치료가 세포매개면역을 저하시킨다는 보고들이 있었으나 이를 방사선치료 부위 안의 혈류와 관련해서 고려되지는 않고 있다. 본 연구는 폐암의 방사선치료 후에 발생하는 백혈구 감소, 특히 림프구의 감소를 후향적으로 분석하고, 면역억제의 한 기전으로서 방사선치료 부위 안의 많은 혈액량과 동적인 혈류가 관련될 수 있는지는 알아보고자 한다. 대상 및 방법: 34명의 폐암환자 들을 대상으로 하였으며, 방사선치료 단독군(RT군)이 10명, 방사선치료와 화학요법병용군(RT/CT군) 16명, 화학요번 단독군(CT군)이 8명이었다. 말초혈액의 전체 백혈구수와 림프구수, 전체 백혈구수 중 림프구수의 비율(림프구 율)을 방사선치료 전중후에, 화학요법 전후에 측정하였는데 방사선치료 중에는 매 주마다 검사를 하였고, 화학요법과 방사선치료 후에는 좀 더 긴 간격으로 하였다. 환자의 특성과 병변의 특성은 세 군 간에 통계적으로 유의한 차이를 보이지 않았다. 치료방법에 있어서도 RT군과 RT/CT군 사이에 총 방사선량, 분할조사선량, 치료면적, 치료용적은 통계학적으로 유의한 차이는 없었다. 방사선치료를 시행한 군(RT군, RT/CT군)과 방사선치료를 시행하지 않는 군(CT군)의 평균 추적기간은 각각 6개월과 8개월이었다. 결과: 치료 후 전체 백혈구수의 변화는 다른 치료군 간에 의미 있는 차이는 보이지 않았다. 방사선치료를 시행한 RT군과 RT/CT군은 방사선치료 후 훨씬 낮은 림프구수와 림프구 율을 보였다. 치료 전 림프구수와 최종 림프구수 사이의 감소는 방사선치료를 시행한 군과 시행하지 않은 군 간에 통계학적으로 유의한 차이를 보였다(p=0.044). 또한 림프구 율에 있어서도 치료 전과 최종 림프구 율 사이의 감소는 방사선치료를 시행한 군과 시행하지 않은 군 간에 통계학적으로 유의한 차이를 보였다(p=0.037). 결론: 림프구 감소증은 화학요법만을 시행한 경우보다 방사선치료를 시행한 경우에 더 현저하였다. 그리고 이러한 림프구 감소중이 폐암의 흉부 방사선치료 후 면역감소의 한 원인이 될 수도 있겠다. 저 선량의 방사선조사 후 림프구의 아포토시스 유도를 보여준 이전의 몇몇 연구들을 함께 생각해 볼 때, 조심스럽게 제안하고 싶은 것은 혹시 본 연구에서 보이는 림프구 감소증이 방사선조사야 내의 많은 혈액량이나 역동적인 혈류와 약간의 관련성이 있을 수도 있다는 것이다. Purpose: This study was undertaken to retrospectively evaluate white blood cell kinetics, especially lymphocyte depression after different treatments, and to find the correlation between immunosuppression and large blood volume and dynamic blood flow within the mediastinal radiotherapy (RT) field in lung cancer. Materials and Methods: Thirty-four patients with lung cancer were retrospectively evaluated; 10 patients had only radiotherapy (RT group), 8 had chemotherapy (CT group_ and 16 had chemotherapy and radiotherapy (RT/CT group). The mean follow-up periods of the RT-including groups (RT group and RT/CT group) and the RT-excluding group (CT group) were 6 and 8 months, respectively. Complete blood cell counts including lymphocyte percentage (%) were checked weekly during RT but less frequently during CT and after RT. Results: Changes in total white blood cell counts were not significantly different among the three groups. The lymphocyte count and lymphocyte % were much lower in the RT-including groups than in the RT-excluding group. The difference between pre-treatment and final lymphocyte count and the difference between pre-treatment and final lymphocyte % were significant (p=0.044, and p=0.037) between the RT-including groups and the RT-excluding group. Conclusion: Lymphopenia was more marked after treatment containing RT than CT only. Lymphopenia may be one cause of a compromised immune system after mediastinal irradiation in lung cancer. We suggest cautiously that previous studies showing evidence of lymphocyte apoptosis after low-dose irradiation and large blood volume and dynamic blood within the RT fields could be somewhat related to lymphopenia after mediastinal irradiation.

Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer

Feiya Shi,Alison K. Yoder,Claire Mach,Shraddha Dalwadi,Matthew L Anderson,Tracilyn R Hall,Michelle S Ludwig 대한산부인과학회 2022 Obstetrics & Gynecology Science Vol.65 No.2

ObjectiveTo evaluate the prognostic significance of hematological toxicities during cervical cancer treatment. MethodsPatients treated for cervical carcinoma with definitive chemoradiation were identified. Toxicities were assessed duringweeks 1 to 6 of concurrent external beam radiation and chemotherapy. Outcomes were analyzed using Cox regressionanalysis. ResultsOne hundred twenty-one patients with Federation of Gynecology and Obstetrics stage I-III disease were eligible foranalysis. Median age at diagnosis was 45 years (interquartile range, 40-52) with median follow-up time of 34 months(95% confidence interval, 30.8-37.2). All patients experienced some grade of hematologic toxicity. The most commongrade 3+ toxicities were low absolute lymphocyte count (n=115, 95%), low white blood cell count (n=21, 17%), andanemia (n=11, 9%). The most common grade 4 toxicity was lymphopenia, experienced by 36% of patients (n=44). Grade 4 lymphopenia was associated with reduced overall survival (hazard ratio [HR], 4.5; P=0.005), progressionfreesurvival (HR, 3.4; P=0.001), and local control (HR, 4.1; P=0.047). Anemia grade 3, 4 was also associated withreduced overall survival (HR, 4.1; P=0.014). After controlling for disease and treatment variables, grade 4 lymphopeniaremained significantly associated with reduced overall survival (HR, 9.85; P=0.007). The association with grade 4lymphopenia only remained significant in women of Hispanic ethnicity. ConclusionSevere lymphopenia was associated with reduced overall survival and progression-free survival in Hispanic womenundergoing definitive chemoradiation for cervical cancer, but not associated with outcomes in non-Hispanic women.

Analysis of in vitro apoptosis induced by virulent Korean isolate of classical swine fever virus in peripheral blood B cell line

Kim, Seon-Mi,Lim, Seong-In,Song, Jae-Young,Hyun, Bang-Hun The Korean Society of Veterinary Science 2012 大韓獸醫學會誌 Vol.52 No.4

Classical swine fever (CSF) is a highly contagious disease among swine that has an important economic impact on worldwide. One clinical symptom of CSF is leukopenia, in particular lymphopenia, which is a characteristic event that occurs early in the course of CSF. Though lymphopenia associated with apoptosis, the pathogenic mechanism underlying the lymphopenia has not been well studied. To understand these mechanisms, we investigated the response of porcine B cell lines to infection with SW03, virulent strain isolated from swine tissue in Korea. This study demonstrated that SW03-infected L35 cell were induced apoptosis through the detection of activated caspase-3. In addition, SW03 infection leaded to alterations in pro-apoptotic, Bax, and anti-apoptotic, Bcl-xL proteins of Bcl-2 family. Our results would suggest that SW03-infected L35 cells induced apoptosis via intrinsic mitochondrial pathway.