BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
BACKGROUND Thrombocytopenia is a common complication of invasive liver abscess syndrome(ILAS)by Klebsiella pneumoniae(K.pneumoniae)infection,which indicates severe infection and a poor prognosis.However,the presence o...BACKGROUND Thrombocytopenia is a common complication of invasive liver abscess syndrome(ILAS)by Klebsiella pneumoniae(K.pneumoniae)infection,which indicates severe infection and a poor prognosis.However,the presence of leukopenia is rare.There are rare reports on leukopenia and its clinical significance for ILAS,and there is currently no recognized treatment plan.Early and broad-spectrum antimi-crobial therapy may be an effective therapy for treating ILAS and improving its prognosis.CASE SUMMARY A 55-year-old male patient who developed fever,chills,and abdominal distension without an obvious cause presented to the hospital for treatment.Laboratory tests revealed thrombocytopenia,leukopenia,and multiple organ dysfunction.Imaging examinations revealed an abscess in the right lobe of the liver and thromboph-lebitis,and K.pneumoniae was detected in the blood cultures.Since the patient was diabetic and had multi-system involvement,he was diagnosed with ILAS accom-panied by leukopenia and thrombocytopenia.After antibiotic treatment and sys-temic supportive therapy,the symptoms disappeared,and the patient’s condition almost completely resolved.CONCLUSION Leukopenia is a rare complication of ILAS,which serves as an indicator of adverse prognostic outcomes and the severity of infection.展开更多
Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms.Studies have documented a prevalence of thrombocytopenia,leukopenia,and anemia in patients with compens...Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms.Studies have documented a prevalence of thrombocytopenia,leukopenia,and anemia in patients with compensated cirrhosis of 77.9%,23.5%,and 21.1%,respectively.These abnormalities carry significant clinical implications,including considerations for invasive procedures,infection risk,bleeding risk,and prognosis.Previously,cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagula-tion tests such as prothrombin time,partial thromboplastin time,international normalized ratio,and thrombocytopenia.However,this understanding has evol-ved,and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events.Hemostasis in cirrhosis patients presents a complex pheno-type,with procoagulant and anticoagulant abnormalities offsetting each other.This multifactorial phenomenon is inadequately reflected by routine laboratory tests.Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity.Bleeding is primarily associated with portal hypertension,endothelial dysfunction,mechanical vessel injury,dissem-inated intravascular coagulation,endotoxemia,and renal injury.This review comprehensively outlines hematologic index abnormalities,mechanisms of hemostasis,coagulation,and fibrinolysis abnormalities,limitations of laboratory testing,and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.展开更多
Objective： To evaluate the efficacy and safety of sodium copper chlorophyllin （trademarked as ＂Yebaike Tablet （叶拜克） which is abbreviated as YBK in treating leukopenia. Methods： One hundred and five patients w...Objective： To evaluate the efficacy and safety of sodium copper chlorophyllin （trademarked as ＂Yebaike Tablet （叶拜克） which is abbreviated as YBK in treating leukopenia. Methods： One hundred and five patients with leukopenia caused by various factors were randomized into 3 groups. The 60 patients in the YBK group took orally YBK Tablets at the dose of 40 mg, three times per day, the 30 patients in the leucogen group were treated with Leucogen Tablets （利血生片） at the dose of 20 mg, three times per day, and the 15 patients in the placebo group were administered with vitamin C tablets 100 mg, three times per day. All the subjects were treated for 1 month. The change of peripheral leucocytes count after treatment and adverse drug reaction that occurred in patients were studied. Results： In the 60 patients treated with YBK, the treatment proved to be markedly effective in 34 cases, effective in 17 and ineffective in 9, the total effective rate being 85%, which was significantly higher than that in the placebo group （26.7%, P〈0.01） and similar to that in the leucogen group （83.3 %, P〉0.05）. No adverse reaction was found in the treatment course. Conclusion： YBK can be used in the treatment of leukopenia caused by various factors, satisfactory in efficacy and safe in use.展开更多
Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and w...Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.展开更多
AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two pat...AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.展开更多
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
基金Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
基金Supported by the 2022 Nanjing Health Science and Technology Development Special Fund Support Project,No.YKK22240.
文摘BACKGROUND Thrombocytopenia is a common complication of invasive liver abscess syndrome(ILAS)by Klebsiella pneumoniae(K.pneumoniae)infection,which indicates severe infection and a poor prognosis.However,the presence of leukopenia is rare.There are rare reports on leukopenia and its clinical significance for ILAS,and there is currently no recognized treatment plan.Early and broad-spectrum antimi-crobial therapy may be an effective therapy for treating ILAS and improving its prognosis.CASE SUMMARY A 55-year-old male patient who developed fever,chills,and abdominal distension without an obvious cause presented to the hospital for treatment.Laboratory tests revealed thrombocytopenia,leukopenia,and multiple organ dysfunction.Imaging examinations revealed an abscess in the right lobe of the liver and thromboph-lebitis,and K.pneumoniae was detected in the blood cultures.Since the patient was diabetic and had multi-system involvement,he was diagnosed with ILAS accom-panied by leukopenia and thrombocytopenia.After antibiotic treatment and sys-temic supportive therapy,the symptoms disappeared,and the patient’s condition almost completely resolved.CONCLUSION Leukopenia is a rare complication of ILAS,which serves as an indicator of adverse prognostic outcomes and the severity of infection.
文摘Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms.Studies have documented a prevalence of thrombocytopenia,leukopenia,and anemia in patients with compensated cirrhosis of 77.9%,23.5%,and 21.1%,respectively.These abnormalities carry significant clinical implications,including considerations for invasive procedures,infection risk,bleeding risk,and prognosis.Previously,cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagula-tion tests such as prothrombin time,partial thromboplastin time,international normalized ratio,and thrombocytopenia.However,this understanding has evol-ved,and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events.Hemostasis in cirrhosis patients presents a complex pheno-type,with procoagulant and anticoagulant abnormalities offsetting each other.This multifactorial phenomenon is inadequately reflected by routine laboratory tests.Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity.Bleeding is primarily associated with portal hypertension,endothelial dysfunction,mechanical vessel injury,dissem-inated intravascular coagulation,endotoxemia,and renal injury.This review comprehensively outlines hematologic index abnormalities,mechanisms of hemostasis,coagulation,and fibrinolysis abnormalities,limitations of laboratory testing,and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.
文摘Objective： To evaluate the efficacy and safety of sodium copper chlorophyllin （trademarked as ＂Yebaike Tablet （叶拜克） which is abbreviated as YBK in treating leukopenia. Methods： One hundred and five patients with leukopenia caused by various factors were randomized into 3 groups. The 60 patients in the YBK group took orally YBK Tablets at the dose of 40 mg, three times per day, the 30 patients in the leucogen group were treated with Leucogen Tablets （利血生片） at the dose of 20 mg, three times per day, and the 15 patients in the placebo group were administered with vitamin C tablets 100 mg, three times per day. All the subjects were treated for 1 month. The change of peripheral leucocytes count after treatment and adverse drug reaction that occurred in patients were studied. Results： In the 60 patients treated with YBK, the treatment proved to be markedly effective in 34 cases, effective in 17 and ineffective in 9, the total effective rate being 85%, which was significantly higher than that in the placebo group （26.7%, P〈0.01） and similar to that in the leucogen group （83.3 %, P〉0.05）. No adverse reaction was found in the treatment course. Conclusion： YBK can be used in the treatment of leukopenia caused by various factors, satisfactory in efficacy and safe in use.
基金supported by the Key Problem Tackling Project for Cancer Therapy, China (Grant No. 12ZCDZSY15600)
文摘Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.
文摘AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.
