High Ferritin Level and Malnutrition Predict High Risk of Infection-Related Hospitalization in Incident Dialysis Patients: A Japanese Prospective Cohort Study

2016 ◽  
Vol 42 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Sawako Kato ◽  
Bengt Lindholm ◽  
Yukio Yuzawa ◽  
Yoshinari Tsuruta ◽  
Kana Nakauchi ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Hospital Admissions ◽  
Ferritin Level ◽  
Nutrition Status ◽  
Rank Test ◽  
Risk Of Infection ◽  
Dialysis Patients ◽  
Clinical Biomarkers ◽  
Kaplan Meier ◽  
Increased Risk

Aims: The aim of the study was to clarify the relationship between serum ferritin and infectious risks. Methods: We evaluated all hospital admissions due to infections, clinical biomarkers and nutrition status in 129 incident Japanese dialysis patients during a median follow-up of 38 months. Results: Kaplan-Meier analysis revealed that the period without infections requiring hospitalization was significantly shorter in ferritin > median (82.0 ng/ml) group than in the ferritin < median group (log-rank test 4.44, p = 0.035). High ferritin was associated with significantly increased relative risk of hospitalization for infection (Cox hazard model 1.52, 95% CI 1.06-2.17). The number of hospitalization days was gradually longer in patients with high ferritin levels and malnutrition. Conclusion: Although serum ferritin levels were low, and doses of iron administered to dialysis patients in Japan are generally lower than in Western countries, an elevated ferritin level was associated with increased risk of infection, particularly in patients with poor nutritional status.

Hydroxyurea in the Management of Pediatric Sickle Cell Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4818-4818
Author(s):  
Amal M. El-Beshlawy
Keyword(s):  
Blood Transfusion ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Hospital Admissions ◽  
Ferritin Level ◽  
Laboratory Data ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Increased Risk ◽  
The Mean

Abstract Low levels of fetal hemoglobin (HbF) in sickle cell disease (SCD) patients (pts) are associated with a variety of vaso-occlusive complications and an increased risk of early death. Raising HbF levels can reduce the effect of the disease. Hydroxyurea (HU) reduces the production of HbS containing red cells and favors the production of HbF containing red cells. HU has bean used successfully in the management of adults with SCD but still there is a limited data on its efficacy and safety in pediatric age group. This study reviews our clinical experience with HU in the treatment of pediatric pts with SCD attending the Pediatric Hematology Clinic of Cairo University. Sixty SCD pts from 2001 to 2007 who received HU over the period of 6 years (yrs) and who continued therapy for at least 6 months were included. Four pts were excluded because of non compliance to treatment. Response to HU was assessed both clinically and by laboratory findings. Pts were considered responders if they showed ≥50% improvement in clinical and laboratory data. These data included number of blood transfusions/yr, vasoocclusive crisis (VOC)/yr requiring admission to the emergency unit, hospital admissions/yr. Laboratory data included Hb (g/dl), MCV (fl), HbF%, total leucocytic count (TLC), (×103/ml) absolute neutrophil count (ANC), platelets (×103/ml) and reticulocytic count (%) and serum ferritin level (ng/ml). Fifty six pts (44 children and 12 adults [≥ 18 yrs]) were included. Their mean age was 14.05 ± 5.3 yrs (range of 6–28 yrs). Thirty seven were females and 19 males. Twenty four (43%) were sickle-β thalassemia while 32 (57%) were homozygous sickle cell anemia (SS). Splenectomy was done for 26 pts (46.5%), 17 before and 9 after start of HU. Forty four (79%) received blood transfusion &gt; 5 times per yr and 12 had sporadic transfusions. Forty pts (71%) were HCV positive. The main indications for starting HU therapy were frequent VOC, transfusion dependency and acute chest syndrome (91%, 86% and 16% respectively). Other indications included hepatic crisis (5%), bone infarction (7%), sequestration crisis (5%) and pulmonary hypertension in one case. HU was started in a dose of 15mg/kg/day with careful monthly monitoring for side effects. There was no attempt to achieve maximum tolerated dose. Dose increase or decrease was done depending on clinical and laboratory response with a maximum dose of 30mg/kg/day. The mean dose of HU was 15.8mg/kg/day (range 10–30 mg/kg/day) and the mean duration of therapy was 3.25 yrs (range of 0.5–6 yrs). Forty four pts (79%) were found to be responders. There was a significant (p&lt;0.05) improvement in all clinical parameters with VOC/yr reduced from a mean of 6 to 1.98, hospitalization/yr from 3 to 0.32, blood transfusion/yr from 9.25 to 1.45. The mean Hb level of responders increased from 7.58g/dl before HU to 8.01g/dl after HU, although not statistically significant, 28/44 pts (63.64%) showed increase in Hb varies between 2-&lt;1g/dl. Patients who did not show increase in Hb level (16/44) were clinically stable and had decreased number of blood transfusion by &gt;50% or stop blood transfusion. Responders showed a significant decrease in TLC, ANC, Retics and serum ferritin (P values 0.002, 0.019, 0.000, 0.001 respectively). Significant increase in HbF and MCV (p= 0.000, 0.001 respectively) was also observed. HU toxicity was defined by &gt; 3 fold increase in ALT, platelet count &lt; 80,000 μl, ANC &lt;1500 or increase in serum creatinine &gt;50% above baseline. Twenty pts (36%) showed signs of HU toxicity: elevated ALT (n=9), neutropenia (n=7), thrombocytopenia (n=1), unexplained jaundice (n=1) and both neutropenia and jaundice (n=2). Thirteen pts continued therapy with reduction of the dose or temporary stopping of HU while 7 stopped HU. It was noticed that all pts who developed hepatotoxicity were HCV positive (p= 0.036). It was also shown that hepatotoxicity was significantly higher among those receiving Deferiprone with HU (n=20) (p=0.001). There was no relation between response to HU and patients’ age, sex, spleen status or phenotype. HU provides the best available strategy to achieve clinical and hematological improvement in SCD in pediatrics, but requires periodic monitoring of blood count and ALT levels especially for HCV positive pts and those on Deferiprone therapy

scholarly journals AB0619 PROGNOSTIC FACTORS OF PATIENTS WITH ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS COMPLICATED WITH INTERSTITIAL PNEUMONIA -A JAPANESE SINGLE CENTER STUDY-

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1605.1-1605
Author(s):  
A. Umeda ◽  
M. Sawada ◽  
N. Watanabe ◽  
M. Suzuki ◽  
T. Naganawa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Interstitial Pneumonia ◽  
Serum Ferritin ◽  
Protective Factor ◽  
Detection System ◽  
Ferritin Level ◽  
Multivariable Analysis ◽  
University Hospital ◽  
Rank Test ◽  
Roc Curve Analysis

Background:Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive dermatomyositis (DM) is frequently associated with rapidly progressive interstitial pneumonia (RPIP), whose prognosis is assumed to be poor[1]. Although outcome of DM-RPIP has been reported to be improved by early immunosuppressive therapy, we still experience the cases with severe outcome. Only several reports mentioned the prognostic factors and they have not been fully elucidated.Objectives:To identify the predictors of prognosis in patients with anti-MDA5 Ab-positive DM associated with interstitial pneumonia (DM-IP).Methods:Anti-MDA5 Ab-positive DM-IP patients admitted to Fujita Health University Hospital between January 2010 and October 2019 were consecutively included and stratified into 2 groups, the survived and the deceased groups. DM was diagnosed according to the criteria proposed by Bohan and Peter[2]. Clinically amyopathic DM was diagnosed according to the criteria proposed by Sontheimer [3]. Diagnosis of IP was based on findings of high resolution CT scan (HRCT). The definition of RPIP was rapid exacerbation of hypoxemia or HRCT findings in a period of days to one month after the onset. Clinical features and prognosis of the patients were collected retrospectively and compared between groups. Candidates of predictors are extracted by the univariable analysis using Fisher’s exact test for dichotic parameters and Wilcoxon signed-rank test for continuous parameters and multivariable analysis using logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was examined to obtain the cut-off level. Survival was examined using Kaplan-Meier method and Log-rank test.Results:Twenty-one patients were involved. Eight were deceased and 13 were survived. The deceased group had a higher ratio of male (75% versus 25%, p= 0.018). All deceased cases were with RPIP and 67 % in the survived cases. Levels of serum ferritin (4490 versus 646 ng/mL, p = 0.0026), CRP (2.1 versus 0.9 mg/dL, p = 0.0490), CK (1150 versus 290 U/L, p = 0.017), AST (194 versus 108 U/L, p = 0.025) and LDH (674 versus 368 U/L, p = 0.011) were higher in the deceased group. Interestingly, skin ulcers were tended to be more frequent (12.5% versus 87.5%, p= 0.0587), and anti-SS-A antibody was also more frequently detected (14.3% versus 85.7%, p=0.0072) in the survived group. Using ROC analysis cut-off values were 963 ng/mL for serum ferritin level (sensitivity 100%, specificity 83%), 0.7 mg/dL for CRP (sensitivity 75%, specificity 69%), 308 U/L for CK (sensitivity 88%, specificity 77%), 62 U/L for ALT (sensitivity 100%, specificity 62%), and 454 U/L for LDH (sensitivity 88%, specificity 77%). Patients were divided into two groups based on these cut-offs or based on dichotic parameters and survival was examined between 2 groups. Except CRP and anti-SS-A antibody, survival was significantly worse in parameter-positive or higher groups. Interestingly, anti-SS-A antibody-positive group had better outcome compared with those without.Conclusion:In our analysis, novel candidates such as serum CK, AST, and LDH levels were newly extracted and parameters previously reported was also included and those were also associated with the clinical outcome. In addition, anti-SS-A antibody was identified as a novel protective factor associated with a good outcome.References:[1]Nakashima R, Hosono Y, Mimori T. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus 2016;25:925-33.[2]Bohan A, Peter JB. Polymyositis and dermatomyositis. N Eng J Med 1975;292:344-7.[3]Sontheimer RD. Dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. Dermatol Clin 2000;20:387-408.Disclosure of Interests:None declared

scholarly journals Increased Monocyte/Lymphocyte Ratio as Risk Marker for Cardiovascular Events and Infectious Disease Hospitalization in Dialysis Patients

2021 ◽  
pp. 1-9
Author(s):  
Reiko Muto ◽  
Sawako Kato ◽  
Bengt Lindholm ◽  
Abdul Rashid Qureshi ◽  
Takuji Ishimoto ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Rank Test ◽  
Differential Count ◽  
Dialysis Patients ◽  
Cox Models ◽  
Lymphocyte Ratio ◽  
Relative Risks ◽  
Log Rank Test ◽  
Increased Risk ◽  
Laboratory Biomarkers

<b><i>Introduction:</i></b> In dialysis patients, cardiovascular disease (CVD) and infectious disease contribute to poor clinical outcomes. We investigated if a higher monocyte/lymphocyte ratio (MLR) is associated with an increased risk of CVD events and infectious disease hospitalizations in incident dialysis patients. <b><i>Methods:</i></b> In an ongoing observational prospective cohort study, 132 Japanese dialysis patients (age 58.7 ± 11.7 years; 70% men) starting dialysis therapy were enrolled and followed up for a median of 48.7 months. Laboratory biomarkers, including white blood cell count and its differential count, were determined at baseline. Event-free time and relative risks (RRs) were calculated using the Kaplan-Meier curves and Cox models, respectively. <b><i>Results:</i></b> When divided into 2 groups according to median MLR (0.35 [range, 0.27–0.46]), the periods without CVD events were significantly shorter in the high MLR group than in the low MLR group (log-rank test = 5.60, <i>p</i> = 0.018). The RR of CVD events, after adjusting for age, sex, and diabetes, was 2.43 (1.22–4.84) in the high MLR group compared to the low MLR group. The periods without infections requiring hospitalization were also shorter (log-rank test = 4.16, <i>p</i> = 0.041). The RR of infections requiring hospitalization was 1.98 (1.02–3.83) after the same adjustments. The number of CVD events was higher in the high MLR group (18.6 events per 100 person-years at risk [pyr]) than the low MLR group (11.1 events per 100 pyr). The duration of infectious disease hospitalization was longer in the high MLR group (6.3 days per pyr) than in the low MLR group (2.8 days per pyr). <b><i>Conclusion:</i></b> A higher MLR is associated with increased risks of both CVD events and infectious disease hospitalization in dialysis patients.

scholarly journals Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study

2015 ◽  
Vol 114 (7) ◽  
pp. 1064-1071 ◽  
Author(s):  
Hui Ma ◽  
Huandong Lin ◽  
Yu Hu ◽  
Xiaoming Li ◽  
Wanyuan He ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Serum Ferritin ◽  
Carotid Atherosclerosis ◽  
Ferritin Level ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cvd Risk ◽  
Carotid Plaques ◽  
Increased Risk ◽  
Fourth Quartile

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima–media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised β = 0·233, P< 0·001), alanine transaminase (standardised β = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised β = 0·181, P< 0·001), TAG (standardised β = 0·083, P= 0·003), Hb (standardised β = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised β = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Increased BAX Expression Is Associated With an Increased Risk of Relapse in Childhood Acute Lymphocytic Leukemia

Blood ◽  
1999 ◽  
Vol 93 (8) ◽  
pp. 2671-2678 ◽  
Author(s):  
Linda A. Hogarth ◽  
Andrew G. Hall
Keyword(s):  
Internal Control ◽  
Important Determinant ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Increased Risk ◽  
B Lineage ◽  
Induced Apoptosis

Studies in cell lines have indicated that expression of the BCL-2 family of proteins is an important determinant of chemotherapy-induced apoptosis; however, the level of expression of these proteins in childhood acute lymphoblastic leukemia (ALL) has not been extensively reported. Using quantitative Western blotting we have determined the level of expression of BCL-2, BAX, MCL-1, and BCL-X in lymphoblasts from 47 children with ALL (33 at presentation only, 4 at relapse only, and 10 at both presentation and on relapse). Results were determined as a ratio to actin as an internal control. BCL-2, BAX, and MCL-1 were detected in all samples. BCL-XL was only detected in 6 cases (4 at presentation and 2 at relapse) and BCL-XS in none. No correlation was found between expression and white blood cell count, age at diagnosis, gender, or blast karyotype. BCL-2 levels and the BCL/BAX and MCL-1/BAX ratios were found to be significantly higher in B-lineage as compared with T-lineage disease (P < .003, .02, and .02, respectively). No consistent pattern of change in expression was noted in the 10 cases studied at both presentation and relapse. Kaplan-Meier analysis showed a significant correlation between high BAX expression and an increased probability of relapse (P< .05 by the log rank test), suggesting that chemosensitivity in leukemic blasts may be regulated by factors that override the BCL-2 pathway.

Impact of target location on the response of trigeminal neuralgia to stereotactic radiosurgery

2014 ◽  
Vol 120 (3) ◽  
pp. 716-724 ◽  
Author(s):  
Zhiyuan Xu ◽  
David Schlesinger ◽  
Krisztina Moldovan ◽  
Colin Przybylowski ◽  
Xingwen Sun ◽  
...  
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Stereotactic Radiosurgery ◽  
Target Location ◽  
Rank Test ◽  
Root Entry Zone ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Facial Numbness ◽  
The Impact

Object The authors evaluate the impact of target location on the rate of pain relief (PR) in patients with intractable trigeminal neuralgia (TN) undergoing stereotactic radiosurgery (SRS). Methods The authors conducted a retrospective review of 99 patients with idiopathic TN who were identified from a prospectively maintained database and were treated with SRS targeting the dorsal root entry zone with a maximum dose of 80 Gy. Targeting of the more proximal portion of a trigeminal nerve with the 50% isodose line overlapping the brainstem was performed in 36 patients (proximal group). In a matched group, 63 patients received SRS targeting the 20% isodose line tangential to the emergence of the brainstem (distal group). The median follow-up time was 33 months (range 6–124 months). Results The actuarial rate of maintenance of Barrow Neurological Institute (BNI) Pain Score I–IIIa was attained in 89% of patients at 1 year, 81% at 2 years, and 69% at 4 years, respectively, after SRS. Kaplan-Meier analysis revealed that durability of PR was only associated with the proximal location of the radiosurgical target (log-rank test, p = 0.018). Radiosurgery-induced facial numbness (BNI Score II or III) developed in 35 patients, which was significantly more frequent in the proximal group (19 patients [53%] compared with 16 [25%] in the distal group [p = 0.015]). Conclusions The radiosurgical target appears to affect the duration of pain relief in patients with idiopathic trigeminal neuralgia with the target closer to the brainstem affording extended pain relief. However, the proximal SRS target was also associated with an increased risk of mild to moderate facial numbness.

scholarly journals Risk of rehospitalisation and death for vulnerable New Zealand children

2017 ◽  
Vol 103 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Jane Oliver ◽  
Tim Foster ◽  
Amanda Kvalsvig ◽  
Deborah A Williamson ◽  
Michael G Baker ◽  
...  
Keyword(s):  
At Risk ◽  
New Zealand ◽  
Home Environment ◽  
Hospital Admissions ◽  
Discharge Data ◽  
Kaplan Meier ◽  
At Risk Children ◽  
Increased Risk ◽  
Cox Proportional Hazard Models ◽  
Social Environmental

ObjectivesThere is considerable need to improve the effectiveness of healthcare to reduce morbidity and mortality. Child hospitalisations are influenced by determinants of health, including the home environment. Our aims were: (1) To investigate whether children hospitalised with potentially avoidable conditions thought to be associated with the home have an increased risk of rehospitalisation and death, (2) To investigate whether children hospitalised with particular subgroups of potentially avoidable conditions have an increased risk of rehospitalisation and death, (3) To assess the usefulness of these subgroups for identifying at-risk children.DesignWe used four existing groups of potentially avoidable conditions developed based on expert opinion: 1. the potentially avoidable hospitalisations (PAH) group, associated with social/environmental conditions, 2. the potentially avoidable hospitalisations attributable (at least in part) to the home environment (PAHHE) group, 3. the crowding group, and 4. the Ministry of Health (MoH) group. We analysed national New Zealand hospital discharge data (2000–2014). Rehospitalisation and death were described using Kaplan-Meier curves. Group effectiveness for identifying at-risk children was assessed using Cox proportional hazard models with children hospitalised for non-PAH conditions as comparison.ResultsIn total, 1425085 hospital admissions occurred, for 683115 unique children. Rehospitalisation was relatively common (71.0%). Death was rare (0.6%). All groups performed moderately well identifying at-risk children. Children with PAH have increased risk of rehospitalisation (adjusted HR (aHR):2.30–3.60) and death (aHR:3.07–10.44). PAH group had highest sensitivity (75.1%). The MoH group has the highest positive predictive value (rehospitalisation: 86.2%, death: 2.5%).ConclusionsChildren in the MoH group are very likely to benefit from housing interventions. Rehospitalisation and early mortality are useful assessment measures. Rehospitalisation exerts a considerable burden, and child deaths are catastrophic.

scholarly journals Systemic inflammation modulates the ability of serum ferritin to predict all-cause and cardiovascular mortality in peritoneal dialysis patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sha Fu ◽  
Junzhe Chen ◽  
Bo Liu ◽  
Peifen Liang ◽  
Yuchun Zeng ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Serum Ferritin ◽  
Systemic Inflammation ◽  
Cardiovascular Mortality ◽  
Serum Ferritin Level ◽  
Cox Regression ◽  
Ferritin Level ◽  
Ferritin Concentration ◽  
Cox Regression Analysis ◽  
Increased Risk

Abstract Background This study aimed to ascertain whether the correlation of high serum ferritin with mortality is affected by systemic inflammation and to investigate the optimal serum ferritin level for predicting death when inflammation is considered in peritoneal dialysis (PD) patients. Methods We classified 221 patients into four groups according to serum ferritin concentration (100 μg/L) and high-sensitivity CRP (hs-CRP) level (3 mg/L), and followed them regularly from the date of catheterization to Dec 31, 2016, at Sun Yat-Sen Memorial Hospital, China. Clinical and biochemical data were collected at baseline, and clinical outcomes such as all-cause and cardiovascular mortality were assessed. Results During a median follow-up of 35 months (3 ~ 109 months), 50 (22.6%) deaths occurred. Cardiovascular disease (46.0%) was the most common cause of death, followed by infection (10.0%). The Kaplan–Meier survival analysis and log-rank test revealed significantly worse survival accumulation among PD patients with higher serum ferritin (≥100 μg/L) under elevated hsCRP levels (> 3 mg/L) (P = 0.022). A multivariate Cox regression analysis revealed that an increased serum ferritin level was independently associated with a higher risk of all-cause and cardiovascular mortality in PD patients (HR = 3.114, P = 0.021; and HR = 9.382, P = 0.032) with hsCRP above 3 mg/L after adjusting for relevant confounding factors. Conclusion Higher serum ferritin levels were associated with an increased risk of all-cause and cardiovascular mortality in patients undergoing PD only in the presence of elevated hsCRP levels. The correlation of serum ferritin with poor outcome should take into consideration systemic inflammation.

Impact of homozygote variant of bleomycin hydrolase (BLMH) gene on survival after chemotherapy for testicular cancer (TC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5022-5022
Author(s):  
E. C. de Haas ◽  
N. Zwart ◽  
C. Meijer ◽  
H. M. Boezen ◽  
G. van der Steege ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Patient Characteristics ◽  
Cytotoxic Agents ◽  
Rank Test ◽  
Future Research ◽  
Polymorphism Analysis ◽  
Kaplan Meier ◽  
Response To Chemotherapy ◽  
Increased Risk

5022 Background: With bleomycin, etoposide and cisplatin, cure of disseminated TC exceeds 80%. Next to tumor characteristics, response to chemotherapy may be determined by polymorphisms of genes involved in metabolism or target pathways of cytotoxic drugs. We investigated whether the A1450G polymorphic site in the gene for BLMH, an enzyme that inactivates bleomycin, is associated with differences in survival. Methods: Data were collected on survival of non-seminomatous TC patients treated with bleomycin and platinum from 1977–2003. BLMH genotype was determined from genomic DNA by PCR + restriction fragment length polymorphism analysis. The 3 genotypes [AA (wild-type), AG (heterozygote variant) and GG (homozygote variant)] were compared for patient characteristics, prognostic factors and received chemotherapy (Mann-Whitney U or χ2 test) and survival (Kaplan-Meier + log-rank test and Cox regression). Results: Data on BLMH genotype and survival were available for 304/372 patients (82%) with median follow-up of 10 yrs (range 0–27). The 3 genotypes AA (n=140), AG (n=133) and GG (n=31) did not differ significantly with respect to age, IGCCC prognosis, creatinine clearance and received dose of bleomycin and platinum. Overall survival of the GG genotype (61%) was worse than the overall survival of AA and AG combined (83%) (p=0.004), due to worse TC related survival of GG (71%) compared to AA + AG (90%) (p=0.001). Homozygote variants (GG) had a significantly increased risk for TC related death (odds ratio (OR) = 4.97) compared to wildtypes (AA) ( table ). Conclusion: Germline presence of the homozygote variant (GG) of the BLMH gene appears to be an unfavorable prognostic factor for TC related death after chemotherapy, in addition to the commonly used IGCCC prognosis. It is unclear whether this is due to alterations in metabolism or target pathways of bleomycin or other cytotoxic agents, or linkage disequilibrium to a yet unknown involved gene. This needs to be unraveled in future research. [Table: see text] No significant financial relationships to disclose.

Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 3-3
Author(s):  
Grace Lee ◽  
Daniel W. Kim ◽  
Vinayak Muralidhar ◽  
Devarati Mitra ◽  
Nora Horick ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Anal Cancer ◽  
Cox Regression ◽  
Cox Model ◽  
Rank Test ◽  
Anal Squamous Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( < 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( > 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p < 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.

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