1.Serum ferritin and PELOD-2 scores in Critically Ill Septic Children - A cross-sectional single-center study
Gema Nazri Yanni ; Rina Amalia C. Saragih ; Aridamuriany Dwiputri Lubis
Acta Medica Philippina 2024;58(6):64-68
Objective:
This study aims to assess the correlation of ferritin serum level and PELOD-2 score, and determine the effectiveness of ferritin serum level as early indicator of organ dysfunction.
Methods:
This was a cross-sectional study carried out to pediatric patients with sepsis in the Pediatric Intensive Care Unit Haji Adam Malik and Universitas Sumatera Utara hospital from June 2021 – January 2022. Complete blood work was done, and ferritin serum level and PELOD-2 score were measured on the first and third day of hospital stay of all the sixty participants aged 1-18 years old with sepsis. The correlation was measured using Spearman test, with p<0.05 indicating a significant correlation.
Results:
The median level of serum ferritin level was 480 (24.7 – 22652) ng/mL. There were 20% patients with ferritin level <200 ng/mL, 26.7% with ferritin level 200-500 ng/mL, and 53.3% patients with ferritin >500 ng/mL. The median score of PELOD-2 was 4. There was a significant correlation of serum ferritin and PELOD-2 score on day 1 of hospital stay.
Conclusion
The ferritin serum level is effective as an early indicator of organ dysfunction until PELOD-2 score is established. There is a positive correlation between serum ferritin and PELOD-2 score. There is a link between elevated ferritin and worse disease prognosis.
Ferritins
;
Sepsis
;
Infections
2.Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia.
Shi-Xiang ZHAO ; Yuan-Yuan GE ; Zeng-Zheng LI ; Hai-Ping HE ; Cheng-Min SHEN ; Ke-Qian SHI ; Tong-Hua YANG ; Yun-Yun DU
Journal of Experimental Hematology 2023;31(5):1315-1321
OBJECTIVE:
To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).
METHODS:
Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.
RESULTS:
It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.
CONCLUSION
Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans
;
Leukemia, Promyelocytic, Acute/diagnosis*
;
Cytokines/metabolism*
;
Interleukin-10
;
Interleukin-17/metabolism*
;
Interleukin-6/metabolism*
;
Interleukin-5/metabolism*
;
Blood Coagulation Disorders
;
Ferritins
;
Tretinoin
3.Relationship between Iron Metabolic Parameters and Platelet Counts in Blood Donors.
Wen-Juan ZHONG ; Qiu-Fang ZHANG ; Cheng-Yong HUANG ; Ying-Chun CHEN ; Ye-Ping ZHOU ; Jin-Ying CHEN ; Jia ZENG
Journal of Experimental Hematology 2023;31(5):1481-1485
OBJECTIVE:
To investigate the correlation of iron metabolic parameters with platelet counts in blood donors.
METHODS:
A total of 400 blood donors who met requirements of apheresis platelet donation were collected, and their hematological parameters were analyzed. The donors were divided into low ferritin group and normal group, the differences of hematological parameters between the two groups were compared, and the correlation of iron metabolic parameters and routine hematology parameters with platelet counts were analyzed.
RESULTS:
Whether male or female, low ferritin group had higher platelet counts than normal group (P < 0.01). Among the iron metabolic parameters, the platelet counts was negatively correlated with serum ferritin (SF), serum iron (SI), and transferrin saturation (TSAT) (r =-0.162, r =-0.153, r =-0.256), and positively correlated with total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) (r =0.219, r =0.294) in female blood donors. Platelet counts was also negatively correlated with SF, SI and TSAT (r =-0.188, r =-0.148, r =-0.224) and positively correlated with UIBC (r =0.220) in male blood donors. Among the routine hematology parameters, platelet counts was negatively correlated with mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and reticulocyte hemoglobin equivalent (Ret-He) in female blood donors (r =-0.236, r =-0.267, r =-0.213, r =-0.284). Platelet counts was also negatively correlated with MCH, MCHC and Ret-He in male blood donors (r =-0.184, r =-0.221, r =-0.209).
CONCLUSION
In blood donors with low C-reactive protein level, the lower the iron store capacity, the lower the iron utilization, and the platelet counts tends to rise.
Male
;
Humans
;
Female
;
Iron/metabolism*
;
Blood Donors
;
Platelet Count
;
Anemia, Iron-Deficiency
;
Hemoglobins
;
Ferritins
4.Clinical characteristics and diagnostic indicators of macrophage activation syndrome in patients with systemic lupus erythematosus and adult-onset Still's disease.
Hai Hong YAO ; Fan YANG ; Su Mei TANG ; Xia ZHANG ; Jing HE ; Yuan JIA
Journal of Peking University(Health Sciences) 2023;55(6):966-974
OBJECTIVE:
To analyze and compare the clinical and laboratory characteristics of macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and to evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) in different auto-immune diseases contexts and to propose new diagnostic predictive indicators.
METHODS:
A retrospective analysis was conducted on the clinical and laboratory data of 24 SLE patients with MAS (SLE-MAS) and 24 AOSD patients with MAS (AOSD-MAS) who were hospitalized at Peking University People's Hospital between 2000 and 2018. Age- and sex-matched SLE (50 patients) and AOSD (50 patients) diagnosed in the same period without MAS episodes were selected as controls. The cutoff values for laboratory indicators predicting SLE-MAS and AOSD-MAS were determined using receiver operating characteristic (ROC) curves. Furthermore, the laboratory diagnostic predictive values for AOSD-MAS were used to improve the classification criteria for systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS), and the applicability of the revised criteria for AOSD-MAS was explored.
RESULTS:
Approximately 60% of SLE-MAS and 40% of AOSD-MAS occurred within three months after the diagnosis of the underlying diseases. The most frequent clinical feature was fever. In addition to the indicators mentioned in the diagnosis criteria for hemophagocytic syndrome revised by the International Society for Stem Cell Research, the MAS patients also exhibited significantly elevated levels of aspartate aminotransferase and lactate dehydrogenase, along with a significant decrease in albumin. Hemophagocytosis was observed in only about half of the MAS patients. ROC curve analysis demonstrated that the optimal discriminative values for diagnosing MAS was achieved when SLE patients had ferritin level≥1 010 μg/L and lactate dehydroge-nase levels≥359 U/L, while AOSD patients had fibrinogen levels≤225.5 mg/dL and triglyceride levels≥2.0 mmol/L. Applying the 2016 sJIA-MAS classification criteria to AOSD-MAS yielded a diagnostic sensitivity of 100% and specificity of 62%. By replacing the less specific markers ferritin and fibrinogen in the 2016 sJIA-MAS classification criteria with new cutoff values, the revised criteria for classifying AOSD-MAS had a notable increased specificity of 86%.
CONCLUSION
Secondary MAS commonly occurs in the early stages following the diagnosis of SLE and AOSD. There are notable variations in laboratory indicators among different underlying diseases, which may lead to misdiagnosis or missed diagnosis when using uniform classification criteria for MAS. The 2016 sJIA-MAS classification criteria exhibit high sensitivity but low specificity in diagnosing AOSD-MAS. Modification of the criteria can enhance its specificity.
Adult
;
Humans
;
Child
;
Macrophage Activation Syndrome/complications*
;
Arthritis, Juvenile/diagnosis*
;
Still's Disease, Adult-Onset/diagnosis*
;
Retrospective Studies
;
Lupus Erythematosus, Systemic/diagnosis*
;
Fibrinogen
;
Ferritins
5.Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases.
Zhi Jun LUO ; Jia Jia WU ; You SONG ; Chun Li MEI ; Rong DU
Journal of Peking University(Health Sciences) 2023;55(6):1111-1117
Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.
Humans
;
Female
;
Adult
;
Rituximab/therapeutic use*
;
Macrophage Activation Syndrome/etiology*
;
Retrospective Studies
;
Lupus Erythematosus, Systemic/drug therapy*
;
Methylprednisolone/therapeutic use*
;
Lupus Vasculitis, Central Nervous System
;
Fever/drug therapy*
;
Erythema/drug therapy*
;
Hormones/therapeutic use*
;
Anemia
;
Alopecia/drug therapy*
;
Triglycerides/therapeutic use*
;
Ferritins/therapeutic use*
6.Clinical characteristics of children with SARS-CoV-2 Omicron variant infection in Kunming.
Jia Wu YANG ; Chun Hui TANG ; Mei DAI ; Jiang DUAN ; Yan Hong LI ; Jian YANG ; Tao YANG ; Yan GAO ; Deng BAN ; Ji Cai ZHU ; Ting Yun YUAN ; Yin LI ; Hong Min FU
Chinese Journal of Pediatrics 2023;61(10):922-927
Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10th, 2022 to January 9th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8+T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×109 vs. 2.7 (1.3,4.4)×109/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ2=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10-3 pg/L,respectively, t=-20.43, χ2=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4+T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4+T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.
Humans
;
Child
;
Female
;
Male
;
COVID-19
;
COVID-19 Vaccines
;
Retrospective Studies
;
SARS-CoV-2
;
Ferritins
;
Interleukin-6
7.Predictive Value of Acute Phase Proteins on the Prognosis of Patients with Acute Myeloid Leukemia.
Xiu-Ji WU ; Yong-Qing WANG ; Xiao-Yang YANG ; Xue-Shu LIN ; Mei-Hua QIU
Journal of Experimental Hematology 2022;30(4):1086-1093
OBJECTIVE:
To analyze the predictive value of acute phase proteins (APPs) on the prognosis of patients with acute myeloid leukemia (AML).
METHODS:
293 AML patients who met the study requirements from January 2015 to April 2021 were collected, their clinical characteristics and pre-treatment APPs levels [including albumin (ALB), fibrinogen (FIB), C-reactive protein (CRP), Ferritin (FER)] were followed up and investigated. Pearson correlation coefficient was used to analyze the correlation between APPs. Logistic regression was used to analyze the risk factors for mortality in AML patients. ROC curve was used to analyze the predictive value of APP for mortality in AML patients, and Kaplan-Meier survival analysis was used to compare the effect of APPs on complete remission (CR) rate, overall survival (OS), disease-free survival (DFS), and progression-free survival rate (PFS) of AML patients.
RESULTS:
Pearson correlation analysis showed that there were negative correlations between ALB and CRP (r=-0.134, P=0002), as well as ALB and FER (r=-0.148, P=0.001). There were correlations between FER and CRP (r=0361, P<0.001), as well as FER and FIB (r=0.293, P<0.001). Logistic regression analysis showed that advanced age (>50 years) (OR=1.87, 95% CI=1.25-2.15, P<0.001), relapse after treatment (OR=2.11, 95% CI=111-3.18, P=0.003), FLT3-ITD mutation (OR=2.59, 95% CI=1.10-4.12, P<0.001), CRP≥524 mg/L (OR=1.21, 95% CI=1.02-2.14, P=0.024), CFA (CFA=CRP*FIB/ ALB)≥3 (OR=2.41, 95% CI=1.65-6.47, P<0.001), and FER≥1145.58 mg/ml (OR=1.67, 95% CI=1.15-3.75, P<0.001) were the risk factors for the survival of AML patients. ROC curve analysis showed that FER (AUC=0.752, 95% CI=0.681-0823, P<0.001, the best cut-off value=1220.56 mg/ml) and CFA (AUC=0.804, 95% CI=0.741-0.868, P<0.001, the best cut-off value=3.00) had higher predictive value for the survival of AML patients. The remission rate, PFS, DFS, and OS in the low CFA group (CFA≤3) were significantly higher than those in the high CFA group (CFA>3), and the overall mortality rate was lower than that in the high CFA group; the remission rate, PFS, DFS, and OS in the low FER group (FER≤1220.56 mg/ml) were significantly higher than those in the high FER group (FER>1220.56 mg/ml), while the overall mortality rate was lower than that in the high FER group, and the difference is statistically significant.
CONCLUSION
The CFA value and FER level before treatment in AML patients can independently predict the prognosis of patients, and high levels of CFA and FER are associated with poor prognosis of AML patients.
Acute-Phase Proteins/therapeutic use*
;
C-Reactive Protein
;
Disease-Free Survival
;
Ferritins/therapeutic use*
;
Humans
;
Leukemia, Myeloid, Acute/genetics*
;
Middle Aged
;
Mutation
;
Prognosis
;
Remission Induction
;
Retrospective Studies
;
fms-Like Tyrosine Kinase 3
8.Efficacy and Mechanism of Buxue Yimu Pills on Gynecological Anemia: A Combination of Clinical and Network Pharmacology Study.
Yan-Fang WANG ; Yan DENG ; Su-Ying ZHANG ; Dong LIU ; Bin LUO ; Xue WANG ; Miao DENG ; Rui-Lin MA ; Ai-Jun SUN
Chinese journal of integrative medicine 2022;28(12):1072-1080
OBJECTIVE:
To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology.
METHODS:
A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.
RESULTS:
Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified.
CONCLUSION
BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).
Humans
;
Anemia/drug therapy*
;
Anemia, Iron-Deficiency/drug therapy*
;
Ferritins/therapeutic use*
;
Hemoglobins
;
Iron/therapeutic use*
;
Network Pharmacology
;
Drugs, Chinese Herbal
9.Recommendations of EASL clinical practice guidelines on haemochromatosis.
Shan TANG ; Su Jun ZHENG ; Zhong Ping DUAN
Chinese Journal of Hepatology 2022;30(9):934-938
Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 μg/L during the induction phase and <100 μg/L during the maintenance phase.
Male
;
Humans
;
Female
;
Hemochromatosis/therapy*
;
Hemochromatosis Protein/genetics*
;
Carcinoma, Hepatocellular/complications*
;
Iron Overload/genetics*
;
Ferritins
;
Liver Cirrhosis/complications*
;
Iron
;
Fibrosis
;
Liver Neoplasms/complications*
;
Transferrins
10.Efficacy of Chimeric Antigen Receptor T Cell in the Treatment of Refractory/Recurrent B Acute Lymphocytic Leukemia in Children.
Fan YANG ; Tian-Yi WANG ; Wei-Wei DU ; Hai-Long HE ; Pei-Fang XIAO ; Ye LU ; Shao-Yan HU ; Ben-Shang LI ; Jun LU
Journal of Experimental Hematology 2022;30(3):718-725
OBJECTIVE:
To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL).
METHODS:
Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T.
RESULTS:
The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis.
CONCLUSION
CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.
Adolescent
;
Antigens, CD19
;
Child
;
Child, Preschool
;
Chronic Disease
;
Ferritins
;
Humans
;
Immunotherapy, Adoptive
;
Methylprednisolone
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
;
Receptors, Antigen, T-Cell
;
Receptors, Chimeric Antigen/metabolism*
;
Recurrence
;
T-Lymphocytes


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