Rituximab Combination with Anthracyclin Based Chemothrapy Significantly Improved the Outcome of Young Patients with Diffuse Large B-Cell Lymphoma in Low as Well in High Risk Subgroups.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2444-2444 ◽  
Author(s):  
Marek Trneny ◽  
David Belada ◽  
Ingrid Vasova ◽  
Robert Pytlik ◽  
Tomas Kozak ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Prospective Trial ◽  
Young Patients ◽  
Primary Cns Lymphoma ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Cns Lymphoma ◽  
Risk Category ◽  
The Impact

Abstract Background: It has been demonstrated that rituximab with chemotherapy improves the outcome of older pts with DLBCL (Coiffier 2000, 2002, Habermann 2003) regardless risk category as well as the outcome of young patients with low IPI risk (Pfreundschuh, 2004). There is a lack of data on the impact of rituximab in high risk young patients. We have analyzed the outcome of young patients with DLBCL registered in Czech Lymphoma Study Group registry. Patients: 422 pts with newly diagnosed DLBCL younger than 60y have been registered between Jan 1999- Aug 2004. Pts with primary CNS lymphoma, pts with missing data, without anthracyclin based therapy were excluded from the analysis. Total 376 pts were analyzed. All patients received anthracyclin based therapy, 120 received rituximab (R-CT) and 256 chemotherapy only (CT). There were no significant differences between both group, R-CT and CT resp. Age median was 47.5y and 49y. Advanced CS was found in 73 pts (60.8%) and in 137 (53.5%), higher LDH was in 72 pts (60%) and 133 pts (51.9%), extranodal involvement was found in 76 pts (63.3%) and in 66 (25.8%) pts. The aaIPI risk distribution was as follows (R-CT vs CT): low risk 31 (25.8%) and 96 (31.5%), low-intermed. 34 (28.3%) and 70 (27.3%), intermed.-high 38 (31.7%) and 55 (21.5%), high 17 (14.2%) and 35 (13.7%). CHOP reg was used in 79 (65.8%) and 186 (72.7%) resp., intensified CHOP or CHOP with other combination was used in 36 (30.0%) and 52 (20.3%), other CT was used in 1 (0.8%) and 18 (7.0%). HDT with ASCT was used in 38 (32.2%) and 55 (22.0%) (ns). The median follow up was 22 m for R-CT and 44 m for CT group. Results: The estimates for 2y PFS was 85.5 % for R-CT and 66.4% for CT group resp. (p 0.0001). The estimates for 2y OS was 90.7% and 77.6% resp. (0.0007). The differences were significant in low risk (L and LI) as well as high risk (IH and H) group. PFS at 2y was 93.4% and 80.2% resp (p 0.005) and OS was 96.9% and 88.8% resp. (0.02) for low risk group. PFS at 2y was 75.8% and 41.8% resp. (0.0003) and OS was 83.4% and 57.0% resp. (0.0007) for high risk group. Conclusion: We have demonstrated the significance of rituximab combination with CT in young pts with DLBCL in this comparison. Rituximab has significant impact both in low risk pts (consistent with MINT data) as well as in high risk young pts, which has not been described in any prospective trial yet. Figure Figure

Prognostic Indices in Older DLBCL Patients Receiving R-CHOP: An Analysis of the U.S. Intergroup Study (E4494, CALGB 9793).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 813-813
Author(s):  
R.H. Advani ◽  
H. Chen ◽  
T.M. Habermann ◽  
V.A. Morrison ◽  
E. Weller ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Risk Category ◽  
Free Survival ◽  
Prognostic Tool ◽  
The Impact ◽  
The U.S

Abstract Background: We reported that addition of rituximab (R) to chemotherapy significantly improves outcome in DLBCL patients (pt) >60 years (JCO24:3121–27, 2006). Although the IPI is a robust clinical prognostic tool in DLBCL, Sehn et al (ASH 2005: abstract 492) reported that a revised (R) IPI more accurately predicted outcome in pt treated with rituximab-chemotherapy. Methods: We evaluated outcomes of the Intergroup study with respect to the standard IPI, R-IPI, age-adjusted (aa) IPI for evaluable pt treated with R-CHOP alone or with maintenance rituximab. We further assessed a modified IPI (mIPI) using age ≥ 70 y as a cutoff rather than age 60 y. Results: The 267 pt in this analysis were followed for a median of 4 y. Pt characteristics were: age > 70 (48%) (median=69), male 52%, stage III/IV 75%, >1 EN site 30%, LDH elevated 60%, PS ≥2 15%. On univariate analysis all of these characteristics were significant for 3 y failure-free survival (FFS) and overall survival (OS). The IPI provided additional discrimination of risk compared to the R-IPI with significant differences in FFS and OS for 3 vs 4–5 factors. The aa-IPI defined relatively few pt as low or high risk. The impact of age was studied using a cut-off of 70 years in a modified IPI, yielding 4 risk groups as shown below. Conclusions: For pt ≥ 60 treated with rituximab-chemotherapy the distinction between 3 vs 4,5 factors in the IPI was significant.The IPI also provided additional discrimination of risk compared to the R-IPI. In this older group of pt, use of an age cutoff ≥70 y placed more patients in the low risk category. It is of interest to apply the mIPI in other datasets with DLBCL pt >60 y. Group # Factors # Pt % 3y FFS* % 3y OS* *All risk groups significantly different; logrank p < 0.001 **95 % CI: FFS (0.46,0.66), OS (0.58,0.78) ***95 % CI: FFS (0.21,0.45), OS (0.31,0.55) L: Low, LI: Low Intermediate, HI: High Intermediate, H; High IPI L 0–1 12 78 83 LI 2 28 70 80 HI 3 33 56** 68** H 4–5 37 33*** 43*** R-IPI Very Good 0 0 - - Good 1–2 40 72 81 Poor 3–5 60 46 57 aa-IPI L 0 12 78 83 LI 1 35 68 78 HI 2 44 47 59 H 3 9 31 35 mIPI (age ≥ 70) L 0–1 27 77 86 LI 2 28 62 74 HI 3 29 47 58 H 4–5 16 28 36

No Benefit from Rituximab Containing Regimens in Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3615-3615
Author(s):  
Gonzalo Gutiérrez-García ◽  
Luis Colomo ◽  
Neus Villamor ◽  
Leonor Arenillas ◽  
Antonio Martínez ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Primary Cns Lymphoma ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous category of lymphoid tumors that comprises different clinical forms not fully recognized in the WHO classification. In this regard, extranodal (EN) DLBCLs have particular clinicobiological features and outcome, sometimes related to the specific site where the lymphoma arises. Nowadays, rituximab plus chemotherapy (CT) is the gold-standard in the treatment of DLBCL. However, the superiority of rituximab-CT (R-CT) over CT alone has not been addressed for all the clinical subsets of the disease and, in fact, the clinical role of the new therapies might be different for primary nodal or EN DLBCLs. The aim of this study was to assess the impact of rituximab in patients suffering from nodal or EN DLBCL. Two-hundred and thirty non-immunocompromised patients (112M/118F; median age, 61 years) diagnosed with CD20+DLBCL in a single institution between 1997 and 2006 (five years before and after establishing R-CT as the standard treatment in DLBCL) and treated with adriamycin-containing regimens were the subject of the present study. The series included 148 primary nodal and 82 EN DLBCL. Patients with primary CNS lymphoma were excluded and lymphomas arising at Waldeyer ring were considered as nodal DLBCL. The main EN sites were GI (n=26), bone (n=13), soft tissue (n=13), lung/pleura (n=9), liver (n=9), and other (n=12). Main clinico-biological and evolutive variables were analyzed. One hundred nineteen patients received only CT and 111 R-CT. Eighty-seven cases with available information were assigned to germinal center B-cell-like (GCB) (41%) or non-GCB (59%) groups according to the Hans method (Blood2004;103:275–82) based on CD10, BCL6 and MUM1 expression. Main initial features, including the primary nodal or EN origin, international prognostic index (IPI), and GCB/non-GCB categories were similar for CT and R-CT groups. No correlation was observed between the GCB/non-GCB groups and the primary site of the tumor, although nodal lymphomas more frequently expressed MUM1 than EN (69% vs. 31%, respectively; p=0.01). CR rate and 5-year overall survival (OS) according to the treatment arm (CT vs. R-CT) is detailed for the whole series and for the nodal and EN groups in the table and OS curves depicted in the figure. In the whole series, variables predicting poor OS in the multivariate analysis were high-risk IPI (RR 2.5; p<0.001), primary nodal involvement (RR 1.6; p=0.04) and no R-CT treatment (RR 1.9; p=0.002). In the nodal group, IPI and no R-CT maintained the prognostic value, whereas in the primary EN only IPI predicted OS. Moreover, no difference in OS was observed according to the nodal or EN origin in those patients receiving R-CT. Biological subtypes GCB vs. non-GCB did not add predictive information neither in the whole series nor in the nodal or EN groups. In conclusion, patients with primary EN DLBCL seem to have little benefit from the use of R-CT. Nevertheless, this intriguing observation should be confirmed in further prospective studies. Complete response CR (%) 5-years OS (%) CT R-CT CT R-CT *p<0.002 R-CT vs. CT All cases (n=230) 59 79* 46 70* Primary nodal (n=148) 54 78* 34 71* Primary extranodal (n=82) 68 78 70 69 Figure Figure

Independent Validation of the 2008 World Health Organization (WHO) Reclassification of Myelodysplastic Syndromes (MDS) Associated with Ring Sideroblasts

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2686-2686 ◽  
Author(s):  
David P. Steensma ◽  
Curtis A Hanson ◽  
Ayalew Tefferi
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Scoring System ◽  
Who Classification ◽  
Risk Group ◽  
Low Risk ◽  
Risk Category ◽  
Intermediate Risk ◽  
Multilineage Dysplasia ◽  
Ring Sideroblasts

Abstract Background: The 2001 WHO classification of myeloid neoplasms distinguished 2 forms of MDS associated with &gt;=15% ring sideroblasts and &lt;5% marrow blasts: refractory cytopenia with multilineage dysplasia and with ring sideroblasts (RCMD-RS) vs. refractory anemia with ring siderblasts (RARS, erythroid-restricted dysplasia). However, the real prognostic value of separating RCMD-RS from RCMD with &lt;15% ring sideroblasts and from RARS is uncertain, and the WHO has proposed merging RCMD-RS and RCMD in the 2008 classification revision. Furthermore, the WHO-based Prognostic Scoring System (WPSS), proposed by Malcovati and colleagues in 2005 as a dynamic system that overcomes some of the limitations of the 1997 International Prognostic Scoring System (IPSS), has undergone limited independent external validation to date and its applicability to sideroblastic MDS in particular is unclear. We assessed the validity of the 2008 WHO reclassification and the WPSS for MDS cases associated with &gt;=15% ring sideroblasts and a normal blast proportion. Methods: We reviewed WPSS and IPSS component parameters at diagnosis and the clinical outcomes of 465 patients (68% males, median age 72) evaluated at our institution over a 13-year period: 140 with RARS, 114 with RCMD-RS, and 211 with RCMD. Patients were assigned a WPSS score and risk category (very low-risk group=0 points; low=1; intermediate=2, high=3 or 4) by summing 3 subscores: 2001 WHO classification (0 for RARS, 1 point for RCMD or RCMD-RS), IPSS cytogenetic risk group (0=good, 1=indeterminate, 2=poor), and red cell transfusion dependence (0=no, 1=yes). Survival was assessed by Kaplan-Meier estimates, and prognostic factors examined by proportional hazards analysis. Results: The median time until death or last followup was 26 months, and 70% of patients were known to have died. The median survival by WHO MDS subtype was 75 months for RARS, 25 months for RCMD-RS, and 26 months for RCMD (Log-Rank p&lt;0.0001 for RARS vs. either RCMD-RS or RCMD; p=0.60 for RCMD vs. RCMD-RS ). Both the WPSS and IPSS predicted overall survival in patients with ring sideroblasts. Median survival for the patients grouped by WPSS risk category was 89 months for very low risk (n=95), 41 for low risk (n=198), 31 for intermediate risk (n=82), and 11 for high risk (n=91) (p&lt;0.0001, except for low risk vs. intermediate risk, p=0.31). (Very high risk WPSS scores cannot be achieved without excess marrow blasts, and such patients were excluded from this analysis.) Median survival by IPSS was 73 months for low-risk, 33 months for intermediate-1, and 8 months for intermediate 2 (p&lt;0.0001). The IPSS’ predictive power was unchanged if patients with secondary MDS were included or excluded (the IPSS was based on a review of 816 patients with apparently de novo MDS). Conclusions: These data support the WHO’s proposal to merge RCMD and RCMD-RS, and suggest that the adverse prognostic significance of multilineage dysplasia renders the presence of ring sideroblasts unimportant. The WPSS is a valid prognostic tool in patients with MDS associated with ring sideroblasts, but in this subgroup both the WPSS and IPSS stratify patients into 3 risk groups, and the WPSS does not offer additional value over the IPSS. Figure Figure

Assessing a prognostic model for predicting VTE occurrence in cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1577-1577
Author(s):  
Deesha Sarma ◽  
So Yeon Kim ◽  
David H. Henry
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
Low Risk ◽  
Risk Category ◽  
Valuable Insight ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Prophylactic Measures ◽  
Risk Patients

1577 Background: Venous thromboembolism (VTE) poses a significant health risk to cancer patients and is one of the leading causes of death among this population. The most effective way to prevent VTE and reduce its prominence as a public health burden is by identifying high-risk patients and administering prophylactic measures. In 2008, Khorana et al. developed a model that classified patients by risk based on clinical factors. Methods: We conducted a retrospective study to test this model’s efficacy, on 150 patients with cancer receiving chemotherapy at an outpatient oncology clinic between January 1 and August 1, 2011. We aggregated data and assigned points based on the five factors in the Khorana model: site of cancer with 2 points for very high-risk site and 1 point for high-risk site, 1 point each for leukocyte counts more than 11 x 109/L, platelet counts greater than 350 X 109/L, hemoglobin levels less than 100 g/L and/or the use of erythropoiesis-stimulating agents, and BMI greater than 35 kg/m2 (Khorana et al., Blood 2008). Based on this scoring system, patients with 0 points were grouped into the low-risk category, those with 1-2 points were considered intermediate-risk, and those with 3-4 points were classified as high-risk. Results: As shown in the table, VTE incidence for the low-risk group was 1.9%, intermediate-risk group was 3.9%, and high-risk group was 9.1%. Conclusions: High-risk patients were about 4.5 times more likely to develop a VTE than low risk patients. These results provide valuable insight in determining which patients might benefit from prophylaxis and in motivating the design of prospective clinical trials that assess the VTE predictive model in various ambulatory cancer settings. [Table: see text]

Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups

2012 ◽  
Vol 97 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Rika Kihara ◽  
Tomoyuki Watanabe ◽  
Takahiro Yano ◽  
Naokuni Uike ◽  
Seiichi Okamura ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Low Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Identification of Novel Tumor Microenvironment-Related Long Non-coding RNAs to Predict the Prognosis for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Shenglan Huang ◽  
Jian Zhang ◽  
Dan Li ◽  
Xiaolan Lai ◽  
Lingling Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Clinicopathological Parameters ◽  
Kaplan Meier ◽  
The Impact

Abstract Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Tumor microenvironment (TME) plays a vital role in the tumor progression of HCC. Thus, we aimed to analyze the association of TME with HCC prognosis, and construct an TME-related lncRNAs signature for predicting the prognosis of HCC patients.Methods: We firstly assessed the stromal/immune /Estimate scores within the HCC microenvironment using the ESTIMATE algorithm based on TCGA database, and its associations with survival and clinicopathological parameters were also analyzed. Then, different expression lncRNAs were filtered out according to immune/stromal scores. Cox regression was performed to built an TME-related lncRNAs risk signature. Kaplan–Meier analysis was carried out to explored the prognostic values of the risk signature. Furthermore, we explored the biological functions and immune microenvironment feathers in high- and low risk groups. Lastly, we probed the association of the risk signature with the treatment responses to immune checkpoint inhibitors (ICIs) in HCC by comparing the immunophenoscore (IPS).Results: Stromal/immune /Estimate scores of HCC patients were obtained based on the ESTIMATE algorithm. The Kaplan-Meier curve analysis showed the high stromal/immune/ Estimate scores were significantly associated with better prognosis of the HCC patients. Then, six TME-related lncRNAs were screened for constructing the prognosis model. Kaplan-Meier survival curves suggested that HCC patients in high-risk group had worse prognosis than those with low-risk. ROC curve and Cox regression analyses demonstrated the signature could predict HCC survival exactly and independently. Function enrichment analysis revealed that some tumor- and immune-related pathways associated with HCC tumorigenesis and progression might be activated in high-risk group. We also discovered that some immune cells, which were beneficial to enhance immune responses towards cancer, were remarkably upregulated in low-risk group. Besides, there was closely correlation of immune checkmate inhibitors (ICIs) with the risk signature and the signature can be used to predict treatment response of ICIs.Conclusions: We analyzed the impact of the tumor microenvironment scores on the prognosis of patients with HCC. A novel TME-related prognostic risk signature was established, which may improve prognostic predictive accuracy and guide individualized immunotherapy for HCC patients.

scholarly journals Comparative Value of the Assessment of Minimal Residual Disease in Peripheral Blood at Days 8 and 15 By Flow Cytometry in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5270-5270
Author(s):  
Marie Loosveld ◽  
Vanessa Nivaggioni ◽  
Isabelle Arnoux ◽  
Denis Bernot ◽  
Chantal Fossat ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
The Impact ◽  
Minimal Residual

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood, but treatments' progress now allowsto obtain prolonged remission or curein over 90% of the patients. Consequently, therapeutic de-escalation is now an objective for future treatment protocols, providing that biomarkers allow to reliablyidentifygood responders. Among such indicators, low levels of Minimal Residual Disease (MRD) obtained early after induction chemotherapy stand out as good candidates. The latter can be investigated usingmultiparameterflow cytometry (MFC) or real-time polymerase chain reaction (RT-PCR) for immunoglobulins or T-cell receptors (IG TCR) rearrangements. In this study we report the impact on survival of two early points of peripheral blood (PB) MRD assessment by MFC at days 8 and 15 on a cohort of 125 children with B-ALL enrolled in the French FRALLE trial and compared to molecular MRD in the bone marrow (BM) at day 35. Patients and methods. The study enrolled 67 boys and 58 girls and the duration of the study allowed for a median follow up of 52,1months. Median age at diagnosis was 57 months old (range 18 to 196), 101 children were between 1 to 10 years old and 24 were older than 10. Complete blood counts (CBC) at diagnosis showed a median of 6.7x109/L leucocytes (range 0.47 - 151x109/L) and 33% blasts (range 0 to 97%). One hundred and eight children had less than 50x109/L leucocytes while 17 had higher counts. EGIL classification at diagnosis allowed to classify patients as three B-I, 94 B-II, 27 B-III and 1 B-IV. Cytogenetic analyses were performed for 118 patients who were partitioned as follows: low risk n=47, intermediate risk n=55 and high risk n=16 (Harrisson CJ et al., BJH, 2010). Eighty-three patients were in the low risk group and 42 in the high-risk group as described by the FRALLE protocol. Seven patients of the 64 tested had an IKZF1 deletion. During the duration of the study, 20 patients relapsed and 8 died. Corticosensitivitywas defined by less than 1x109/L PB blasts on day 8 andchemosensitivity by less than 5% BM blasts on day 21 on BM smears. PB MRD was assessed in MFC with a single five or ten colors tube adapted to each patient's leukemia associatedimmunophenotypeon a backbone of CD45, CD19, CD10 and CD38. Statistical analyzes examined factors impacting disease-free survival (DFS) using Log rank test and Kaplan-Meier using theMedcalc® software (Ostend, Belgium). P values <0.05 were considered significant. Results None of diagnosis features had any significant impact on DFS: age (p=0,95), risk group (p=0,17), EGIL classification (p=0,55), cytogenetics (p= 0,87), leucocyte count (p=0,36) nor IKZF1 deletion (p=0,2). Of the 125 patients, 9 were corticoresistant, 79 corticosensitive and 37 not evaluable because of less than 1x109/L leucocyte at diagnosis.Corticosensitivity had no impact on DFS (p=0,11). Conversely,chemosensitivity had a significant positive impact on DFS (p= 0,009). Day 8 PB MRD did not oultlineany significantly different DFS, whether considering detectable vs undetectable MRD (p=0.65) or MRD levels (logwisefrom >10-1 to <10-4, p=0,22). Conversely, PB MFC at day 15 appeared highly discriminant. Considering notdetectablevs detectable MRD, 4 years DFS was 91,6+3% vs. 67,6+9% p=0,0013 (Figure 1). Further refining the thresholds of MRD logwisedid not modify the significance (p=0.004; Figure 2). Indeed, DFS at 48 months was 61+15 % (n=16) for MRD >10-3, 74+11% ( n=18) for MRD <10-3->10-4 and 92+3% ( n=91) for MRD<10-4. Comparison of PB MFC MRD on day 15 with day 35 BM molecular MRD showed concordance in 72% of the cases (83 negative/negative and 7 positive/positive, 48 months DFS 94.6+2.7% and 38+20% respectively). Eight patients were negative in PB but positive in BM (DFS 62.5+17%).Twenty seven where positive in PB but negative in BM (DFS 83.5+7.6%).These differences were statistically highly significant (p <0.0001). Conclusion This study demonstrates that even in the good prognosis context of childhood ALL, early MRD retains a highly significant prognostic value. It is of importance that this result was obtained not only on day 35 BM but interestingly, even earlier on day 15 PB. This less invasive procedure can easily be applied, especially for children. It should allow to detectgood responders, with MFC MRD levels below 10-4 for whom a de-escalation of chemotherapy could be considered. Conversely, the detection of blasts by MFC in day 15 PB is worrisome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term safety of growth hormone treatment in childhood: Two large observational studies NordiNet ® IOS and ANSWER

2021 ◽  
Author(s):  
Lars Sävendahl ◽  
Michel Polak ◽  
Philippe Backeljauw ◽  
Joanne C Blair ◽  
Bradley S Miller ◽  
...  
Keyword(s):  
High Risk ◽  
Mortality Risk ◽  
Observational Studies ◽  
Risk Group ◽  
Risk Groups ◽  
Incidence Rates ◽  
Low Risk ◽  
Risk Category ◽  
Gh Treatment

Abstract Context GH treatment has a generally good safety profile; however, concerns of increased mortality risk in adulthood have been raised. Objective Assessing the long-term safety of GH treatment in clinical practice. Design Two multicenter longitudinal observational studies: NordiNet® International Outcome Study (2006–2016, Europe) and ANSWER Program (2002–2016, USA). Setting Data collected from 676 clinics. Patients Pediatric patients treated with GH, classified into three risk groups based on diagnosis. Intervention Daily GH treatment. Main Outcome Measures Incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to the GH dose. Results The combined studies comprised 37,702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130,476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (e.g. with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with &gt;1 AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P = 0.0029 and P = 0.0003, respectively) and the non-SGA subgroup (P = 0.0022 and P = 0.0015, respectively), and for SAEs in the intermediate- and high-risk groups (P = 0.0017 and P = 0.0480, respectively). Conclusions We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group.

scholarly journals CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas

2021 ◽  
Vol 9 ◽  
Author(s):  
Depei Li ◽  
Wanming Hu ◽  
Xiaoping Lin ◽  
Ji Zhang ◽  
Zhenqiang He ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Penalized Regression ◽  
High Risk Group ◽  
Low Risk ◽  
Wild Type ◽  
Immune Microenvironment ◽  
Molecular Features ◽  
The Impact

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

scholarly journals Prevalence of SARS CoV-2 infection among Health Care Workers of a hybrid tertiary COVID 19 hospital in Kerala

2021 ◽  
Author(s):  
Jessy S J ◽  
Shamha Beegum ◽  
Genga Gopakumar ◽  
Bindu G ◽  
Chntha S ◽  
...  
Keyword(s):  
Health Care ◽  
High Risk ◽  
Health Care Workers ◽  
Risk Group ◽  
Previous History ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Category ◽  
Care Workers ◽  
History Of

Back ground and objectives- This study was undertaken to estimate the prevalence of SARS-CoV-2 infection among Health care workers [HCWs] of a hybrid COVID treatment hospital in Kerala. Methods- The study was conducted during 3rd week of January 2021. Among 3550 HCWs, 979 subjects were selected by stratified random sampling and grouped into high risk and low risk category based on job setting. Demographic details and clinical information regarding previous history of COVID 19 were collected at the time of SARS-CoV-2 IgG testing. Results: From 979 subjects, the data with respect to 940 health care workers were analysed. SARS-CoV-2 IgG was detected in 19.1% of HCWs. Seroprevalence among high risk group was 20.3% and that in low risk group was 7.4% [p=0.005]. In high-risk group, seropositivity was noted in 30.54 % of nurses, 19% hospital attenders, 18.9% resident doctors and 6.4% consultant doctors. In those with past history of SARS-CoV-2 infection, seropositivity was 75.4%. In those who were COVID positive during July2020, 33.3% were still IgG reactive. Interpretation and conclusion- The study reported 19.1% SARS CoV-2 IgG reactivity among health care workers in our hospital. Seropositivity was significantly higher in high risk group compared to low risk group. Antibody decay kinetics in our study is comparable to that in published literature. Infection control challenges in hybrid hospitals account for higher seropositivity in this study compared to overall seroprevalence among HCWs in Kerala.

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