scholarly journals High incidence and mortality of Pneumocystis jirovecii infection in anti-MDA5-antibody-positive dermatomyositis: experience from a single center

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Linlin Huang ◽  
Qiong Fu ◽  
Yan Ye ◽  
Yanwei Lin ◽  
Qingran Yan ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Rheumatic Diseases ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Unmet Need ◽  
Pneumocystis Jirovecii ◽  
Cox Regression Analysis ◽  
Cell Counts ◽  
Incidence And Mortality ◽  
High Incidence

Abstract Background Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM. Objectives To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies. Methods In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival. Results The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5− IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05). Conclusion PJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.

scholarly journals POS0885 HIGH INCIDENCE AND MORTALITY OF PNEUMOCYSTIS JIROVECI INFECTION IN ANTI-MDA5-ANTIBODY POSITIVE DERMATOMYOSITIS: EXPERIENCE FROM A SINGLE CENTER

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 698.2-699
Author(s):  
Q. Yan ◽  
S. Chen ◽  
L. Huang ◽  
Q. Fu ◽  
Y. Ye
Keyword(s):  
Mortality Rate ◽  
Rheumatic Diseases ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Rank Test ◽  
Pneumocystis Jiroveci ◽  
Pneumocystis Jiroveci Pneumonia ◽  
Cell Counts ◽  
Incidence And Mortality ◽  
High Incidence

Background:Idiopathic inflammatory myopathies (IIM) was associated with a significantly higher risk of opportunistic infections that including Pneumocystis jiroveci pneumonia(PJP) which is potentially fatal opportunistic infection. However, no prior studies have evaluated the PJP infection in subtypes of IIM.Objectives:To investigate the incidence rate and mortality rate of PJP infection in subgroups of IIM patients according to myopathy specific antibodies.Methods:In the first part, we reviewed 463 consecutive patients with IIM retrospectively to analyze incidence of PJP infection. In the next part, we enrolled 30 consecutive PJP infection patients with any rheumatic disease was to identify the mortality rate and risk factors. Kaplan-Meier curve with log rank test was used to access differences in survival. Univariate and multivariate analyses were performed to identify prognostic factors using Cox regression.Results:We found that 12(7.5%) PJP cases occurred in 160 anti-MDA5-ab-positive DM patients, while only two (0.7%) PJP cases were found in 303 anti-MDA5-ab-negtive DM/PM patients(P < 0.05). PJP infection typically happened in the first two months of the treatment for anti-MDA5-ab-positive DM patients who have a significant decrease in the CD4+ T cell counts and Lymphocyte counts (P < 0.05). Only two (16.7%) anti-MDA5-ab-positive DM patients recover from PJP, with lethally higher mortality than those PJP infection with other rheumatic diseases (83.3% vs. 38.9%, P < 0.05). We found no association between the time to anti-PJP treatment and treatment outcomes in anti-MDA5-ab-positive DM; yet we confirmed in PJP infection with other rheumatic diseases that anti-PJP treatment within 6 days crucially increased the survival (P < 0.05).Conclusion:PJP infection has alarming high incidence and mortality in anti-MDA5-ab-positive DM patients. Unlike PJP infection with other rheumatic diseases, timely treatment for PJP doesn’t improve the prognosis of this particular subtype. Therefore, the necessity of further study of PJP prophylaxis treatment in anti-MDA5-ab-positive DM patients is verified.References:[1]Hsu CY, et al. Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study. ARTHRITIS RES THER 2019, 21(1):211.Acknowledgements:The authors thank Dr. An Sun,Disclosure of Interests:None declared

scholarly journals High Incidence and Mortality of Pneumocystis Jiroveci Infection in Anti-MDA5-Antibody Positive Dermatomyositis: Experience From a Single Center

2021 ◽  
Author(s):  
Linlin Huang ◽  
Qiong Fu ◽  
Yan Ye ◽  
Yanwei Lin ◽  
Qingran Yan ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Incidence Rate ◽  
Rheumatic Diseases ◽  
Cox Regression ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Pneumocystis Jiroveci ◽  
Cell Counts ◽  
Incidence And Mortality ◽  
High Incidence

Abstract Background Idiopathic inflammatory myopathies (IIM) was associated with a significantly higher risk of opportunistic infections that including Pneumocystis jiroveci pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated the PJP infection in subtypes of IIM. Objectives To investigate the incidence rate and mortality rate of PJP infection in subgroups of Idiopathic inflammatory myopathies (IIM) patients according to myopathy specific antibodies. Methods In the first part, 463 consecutive patients with IIM were prospectively followed up for a period of at least one year to analyze incidence of PJP. In the next part, we enrolled 30 consecutive PJP patients with any rheumatic disease were to identify the mortality rate and risk factors by Cox regression. Kaplan-Meier curve with log-rank test was used to access differences in survival. Results We found that the incidence rate of PJP in IIM patients is 3.0/100 person-year, while in MDA5+DM patients is 7.5/100 person-year and in MDA5−IIM patients is 0.7/100 person-year. (P < 0.05). PJP typically happened in the first two months for MDA5 + DM patients who have a significant decrease in the CD4+ T cell counts and Lymphocyte counts (P < 0.05). In PJP + patients, the mortality was lethally higher in MDA5+DM patients than those with other rheumatic diseases (83.3% VS. 38.9%, P < 0.05). Unlike patients with other rheumatic diseases, MDA5 + patients seemed not to benefit from prompt anti-PJP treatment. For patients with other rheumatic diseases, anti-PJP treatment within 6 days was confirmed to crucially increased the survival (P < 0.05). Conclusion PJP has alarming high incidence and mortality in MDA5+DM patients. Timely treatment for PJP does not improve the prognosis of this particular subtype. Therefore, the necessity of further study of PJP prophylaxis treatment in MDA5+DM patients is verified.

scholarly journals Association of Particulate Matter with Autoimmune Rheumatic Diseases among Adults in South Korea

Rheumatology ◽  
2021 ◽  
Author(s):  
Jun Seok Park ◽  
Seulggie Choi ◽  
Kyuwoong Kim ◽  
Jooyoung Chang ◽  
Sung Min Kim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Adverse Effects ◽  
South Korea ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Statistical Significance ◽  
Cox Regression Analysis ◽  
Autoimmune Rheumatic Diseases ◽  
Quartile Group

Abstract Objective The primary objective is to investigate adverse effects of ambient particulate matter (PM) in various size on the incidence of prevalent autoimmune rheumatic diseases (AIRDs): Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), and Systemic Lupus Erythematosus (SLE). Methods We investigated 230,034 participants in three metropolitan cities of South Korea from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. 2008-2009 respective averages of PM2.5 (&lt; 2.5μm) and PMcoarse (2.5μm to 10μm) were linked with participants’ administrative district codes. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis in one- and two-pollutant model. Results Adjusted for age, sex, region, and household income in two-pollutant model, RA incidence was positively associated with 10μg/m³ increment of PM2.5 (aHR = 1.74, 95% CI: 1.06-2.86), but not with PMcoarse (aHR = 1.27, 95% CI: 0.87-1.85). In one-pollutant model, an elevated incidence rate of RA was slightly attenuated (PM2.5 aHR = 1.61, 95% CI: 0.99-2.61; PMcoarse aHR = 1.13, 95% CI: 0.80-1.61), with marginal statistical significance of PM2.5. RA incidence was also higher in 4th quartile group of PM2.5 compared to 1st quartile group (aHR = 1.83, 95% CI: 1.07-3.11). No adverse effects of PM were found on AS or SLE in one- and two-pollutant models. Conclusion Important components of PM10 associated with RA incidence were fine fractions (PM2.5), while no positive association was found between PM and AS or SLE.

scholarly journals Preadmission Statin Use and 90-day Mortality in the Critically Ill

2019 ◽  
Vol 131 (2) ◽  
pp. 315-327 ◽  
Author(s):  
Tak Kyu Oh ◽  
In-Ae Song ◽  
Jae Ho Lee ◽  
Cheong Lim ◽  
Young-Tae Jeon ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Mortality Rate ◽  
Critically Ill ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Cox Regression Analysis ◽  
Statin Dose ◽  
Mortality Hazard Ratio ◽  
Statin Use

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background This study aimed to examine the association between preadmission statin use and 90-day mortality in critically ill patients and to investigate whether this association differed according to statin type and dose. We hypothesized that preadmission statin use was associated with lower 90-day mortality. Methods This retrospective cohort study analyzed the medical records of all adult patients admitted to the intensive care unit in a single tertiary academic hospital between January 2012 and December 2017. Data including preadmission statin use, statin subtype, and daily dosage were collected, and the associations between these variables and 90-day mortality after intensive care unit admission were examined. The primary endpoint was 90-day mortality. Results A total of 24,928 patients (7,396 statin users and 17,532 non–statin users) were included. After propensity score matching, 5,354 statin users and 7,758 non–statin users were finally included. The 90-day mortality rate was significantly higher in non–statin users (918 of 7,758; 11.8%) than in statin users (455 of 5,354; 8.5%; P &lt; 0.001). In Cox regression analysis, the 90-day mortality rate was lower among statin users than among non–statin users (hazard ratio: 0.70, 95% CI: 0.63 to 0.79; P &lt; 0.001). Rosuvastatin use was associated with 42% lower 90-day mortality (hazard ratio: 0.58, 95% CI: 0.47 to 0.72; P &lt; 0.001). There were no specific significant differences in the association between daily statin dose and 90-day mortality. In competing risk analysis, the risk of noncardiovascular 90-day mortality in statin users was 32% lower than that in non–statin users (hazard ratio: 0.68, 95% CI: 0.60 to 0.78; P &lt; 0.001). Meanwhile, cardiovascular 90-day mortality was not significantly associated with statin use. Conclusions Preadmission statin use was associated with a lower 90-day mortality. This association was more evident in the rosuvastatin group and with noncardiovascular 90-day mortality; no differences were seen according to daily dosage intensity.

scholarly journals Comparison of Cefepime-Cefpirome and Carbapenem Therapy for Acinetobacter Bloodstream Infection in a Multicenter Study

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Yea-Yuan Chang ◽  
Ya-Sung Yang ◽  
Shang-Liang Wu ◽  
Yung-Chih Wang ◽  
Te-Li Chen ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Bloodstream Infection ◽  
Antimicrobial Therapy ◽  
Sofa Score ◽  
Cox Regression ◽  
Content Type ◽  
Cox Regression Analysis ◽  
Medical Centers ◽  
Acinetobacter Pittii ◽  
Underlying Diseases

ABSTRACT Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime-cefpirome can be used to treat an Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogen(s) is not clear. This study aimed to compare the efficacy of cefepime-cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centers in Taiwan in 2012 to 2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients). The crude 30-day mortality rates for cefepime-cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime-cefpirome or carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), Acinetobacter baumannii (18.4%), and Acinetobacter pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime-cefpirome therapy was not independently associated with a higher or lower 30-day mortality rate compared to that with the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137 to 1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607 to 31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime-cefpirome or carbapenem monotherapy. The incidence densities of 30-day mortality for cefepime-cefpirome versus carbapenem therapy were 0.40% versus 1.04%, respectively. The therapeutic response of cefepime-cefpirome therapy was comparable to that with carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

scholarly journals Five lncRNAs Associated With Prostate Cancer Prognosis Identified by Coexpression Network Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382096357
Author(s):  
Xiaoyong Gong ◽  
Bobin Ning
Keyword(s):  
Prostate Cancer ◽  
Network Analysis ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Interaction Network ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Normal Prostate ◽  
Cox Regression Analysis ◽  
Incidence And Mortality

Prostate cancer (PCa) is a highly malignant tumor, with increasing incidence and mortality rates worldwide. The aim of this study was to identify the prognostic lncRNAs and construct an lncRNA signature for PCa diagnosis by the interaction network between lncRNAs and protein-coding genes (PCGs). The differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) between PCa and normal prostate tissues were screened from The Cancer Genome Atlas (TCGA) database. The DEPCGs were functionally annotated in terms of the enriched pathways. Weighted gene co-expression network analysis (WGCNA) of 104 PCa samples identified 15 co-expression modules, of which the Turquoise module was negatively correlated with cancer and included 5 key lncRNAs and 47 PCGs. KEGG pathway analyses of the core 47 PCGs showed significant enrichment in classic PCa-related pathways, and overlapped with the enriched pathways of the DEPCGs. LINC00857, LINC00900, LINC00908, LINC00900, SNHG3 and FENDRR were significantly associated with the survival of PCa and have not been reported previously. Finally, Multivariable Cox regression analysis was used to establish a prognostic risk formula, and the patients were accordingly stratified into the low- and high-risk groups. The latter had significantly worse OS compared to the low-risk group (P < 0.01), and the area under the receiver operating characteristic curve (ROC) of 14-year OS was 0.829. The accuracy of our prediction model was determined by calculating the corresponding concordance index (C-index) and risk curves. In conclusion, we established a 5-lncRNA prognostic signature that provides insights into the biological and clinical relevance of lncRNAs in PCa.

scholarly journals Living alone vs. living with someone as a predictor of mortality after a bone fracture in older age

2020 ◽  
Vol 32 (9) ◽  
pp. 1697-1705
Author(s):  
Kaisa Koivunen ◽  
Elina Sillanpää ◽  
Mikaela von Bonsdorff ◽  
Ritva Sakari ◽  
Katja Pynnönen ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Living Arrangements ◽  
Cox Regression ◽  
Living Arrangement ◽  
Living Alone ◽  
Cox Regression Analysis ◽  
Health Decline ◽  
Fracture Time ◽  
Incidence And Mortality

Abstract Background Living alone is a risk factor for health decline in old age, especially when facing adverse events increasing vulnerability. Aim We examined whether living alone is associated with higher post-fracture mortality risk. Methods Participants were 190 men and 409 women aged 75 or 80 years at baseline. Subsequent fracture incidence and mortality were followed up for 15 years. Extended Cox regression analysis was used to compare the associations between living arrangements and mortality risk during the first post-fracture year and during the non-fracture time. All participants contributed to the non-fracture state until a fracture occurred or until death/end of follow-up if they did not sustain a fracture. Participants who sustained a fracture during the follow-up returned to the non-fracture state 1 year after the fracture unless they died or were censored due to end of follow-up. Results Altogether, 22% of men and 40% of women sustained a fracture. During the first post-fracture year, mortality risk was over threefold compared to non-fracture time but did not differ by living arrangement. In women, living alone was associated with lower mortality risk during non-fracture time, but the association attenuated after adjustment for self-rated health. In men, living alone was associated with increased mortality risk during non-fracture time, although not significantly. Conclusion The results suggest that living alone is not associated with pronounced mortality risk after a fracture compared to living with someone.

scholarly journals Survival Analysis of Risk Factors for Mortality in a Cohort of Patients with Tuberculosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yi Xie ◽  
Jing Han ◽  
Weili Yu ◽  
Junping Wu ◽  
Xue Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mortality Rate ◽  
Pulmonary Tuberculosis ◽  
Treatment Effects ◽  
Cox Regression ◽  
Cohort Analysis ◽  
Advanced Age ◽  
Cox Regression Analysis ◽  
Antituberculosis Treatment ◽  
Male Sex

Identify the treatment effects and risk factors for mortality in patients with pulmonary tuberculosis receiving antituberculosis treatment under the Directly Observed Treatment Short-Course (DOTS) program to reduce the mortality rate of tuberculosis. A retrospective cohort analysis was conducted on the outcomes of antituberculosis treatment of 7,032 patients with tuberculosis in the DOTS program, in the Tuberculosis Management Information System from 2014 to 2017 in Tianjin, China. The Kaplan–Meier method and multifactor Cox proportional risk regression model were used to analyze the risk factors for mortality during antituberculosis treatment under DOTS. The success rate of antituberculosis treatment was 90.24% and the mortality rate was 4.56% among 7,032 cases of tuberculosis in Tianjin. Cox regression analysis showed that advanced age, male sex, human immunodeficiency virus (HIV) positivity, first sputum positivity, retreated tuberculosis, and a delayed visit (≥14 days) were risk factors for mortality in patients with pulmonary tuberculosis receiving antituberculosis treatment under DOTS. The treatment effects in patients with pulmonary tuberculosis during antituberculosis treatment under DOTS were positive in Tianjin. Advanced age, male sex, HIV positivity, first sputum positivity, retreated tuberculosis, and a delayed visit (≥14 days) increased the risk for mortality during antituberculosis treatment.

2231HsCRP predicts mortality beyond troponin in 102,337 patients with suspected acute coronary syndrome (CRP-RISK study)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kaura ◽  
A Hartley ◽  
V Panoulas ◽  
B Glampson ◽  
J Davies ◽  
...  
Keyword(s):  
Real World ◽  
Health Informatics ◽  
Cox Regression ◽  
White Cell ◽  
Research Centre ◽  
Troponin Level ◽  
Cox Regression Analysis ◽  
Cumulative Mortality ◽  
Coronary Syndrome ◽  
Cell Counts

Abstract Background The incremental long-term prognostic value of high-sensitivity C-reactive protein (hsCRP) above troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndromes (ACS) is unknown. Purpose We hypothesised that a mildly elevated hsCRP is associated with mortality risk in patients with suspected ACS, independent of troponin level. Methods We used the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients who had a troponin measured at 5 cardiac centres. We excluded patients with clinically abnormal white cell counts and hsCRP >15 mg/L to try limiting the population to those without overt infections, malignancies or systemic inflammatory conditions that may confound our analyses. Patients were divided into four hsCRP groups (<2, 2–4.9, 5–9.9 and 10–15 mg/L) and the association between hsCRP levels and all-cause mortality assessed. Results There were 102,337 patients included in the analysis (hsCRP <2 mg/L (n=38,390), 2–4.9 mg/L (n=27,397), 5–9.9 mg/L (n=26,957) and 10–15 mg/L (n=9,593)). Figure 1A displays cumulative mortality per hsCRP group, revealing increasing mortality with each consecutive group. Figure 1B further stratifies the groups according to dichotomised peak troponin level as positive or negative. This shows the greatest mortality for patients in the highest hsCRP group who also had a positive troponin assay (36.0% at 3 years). In Cox regression analysis with time-dependent covariates, even mildly raised hsCRP was an independent predictor of mortality over time, after adjusting for age, gender, haemoglobin, white cell count, platelet count, creatinine and troponin positivity. There was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3-years (hazard ratio (95% CI) of 1.32 (1.18–1.48) for those with hsCRP 2.0–4.9mg/L, and 1.40 (1.26–1.57), and 2.00 (1.75–2.28) for those with hsCRP 5–9.9 mg/L and 10–15 mg/L, respectively. We explored whether inclusion of hsCRP could better reclassify the population into at-risk mortality groups. The association with 30-day, 1-year and 3-year mortality was assessed using three different risk models (model 1: age, gender, haemoglobin, creatinine; model 2: model 1 plus troponin (positivity versus negativity); model 3: model 2 plus hsCRP groups. For cumulative mortality at each time point, each successive model was better able to discriminate risk than its precursor (p<0.0001); such that inclusion of troponin and hsCRP gave the most robust risk discrimination. Model 3 achieved an AUROC >0.8 at 30 days, 1-year and 3-year mortality, surpassing the use of troponin on its own. Figure 1. Kaplan-Meier mortality curves Conclusions These multi-centre, real-world data from a large cohort of patients with suspected ACS identify hsCRP as a clinically meaningful prognostic marker in addition to troponin levels and point to its potential utility in selecting patients for novel treatments targeting inflammation. Acknowledgement/Funding Funded by NIHR Imperial Biomedical Research Centre (BRC) using NIHR Health Informatics Collaborative data service, supported by OUH, GSTT & UCLH BRCs

Intensification of Mercaptopurine/Methotrexate Maintenance Chemotherapy May Increase the Risk of Relapse for Some Children With Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (7) ◽  
pp. 1332-1339 ◽  
Author(s):  
Kjeld Schmiegelow ◽  
Olle Björk ◽  
Anders Glomstein ◽  
Göran Gustafsson ◽  
Niels Keiding ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Tpmt Activity ◽  
Control Group ◽  
Cox Regression Analysis ◽  
Cell Counts ◽  
Increased Risk ◽  
Risk Of Relapse

Purpose: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). Patients and Methods: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). Results: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P = .00003), high WBC at diagnosis (P = .03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P = .002), and high average neutrophil counts during maintenance therapy (P = .0009), with a significant interaction between sex and randomization group (P = .0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P = .001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P < .0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P = .03; boys 19.3 v 18.0 U/mL, P = .04). Conclusion: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.

Sign in / Sign up

Export Citation Format

Share Document