scholarly journals Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3554
Author(s):  
Taizo Uchimoto ◽  
Kazumasa Komura ◽  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Kazuhiro Takahashi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Model ◽  
Risk Group ◽  
Objective Response ◽  
Collaborative Study ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Neutrophil Lymphocyte Ratio ◽  
Poor Risk ◽  
Metastatic Sites

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

CGE19-065: Number of Somatic Mutations Is an Independent Predictor of Overall Survival in Acute Myeloid Leukemia

2019 ◽  
Vol 17 (3.5) ◽  
pp. CGE19-065
Author(s):  
Zin W. Myint ◽  
Rani Jayswal ◽  
Ranjana Arora ◽  
Gregory P. Monohan ◽  
Amit Goldberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Poor Risk ◽  
Baseline Characteristics ◽  
Clinically Significant

Purpose: Acute myeloid leukemia (AML) is characterized by multiple somatically acquired mutations that affect genes of different functional categories. It has been well established in myelodysplastic syndrome (MDS) that the cumulative number of somatic mutations has an impact on overall survival. However, no such data exist for AML. In this study, we sought to determine the number of clinically significant somatic mutations for each cytogenetically defined risk group of AML and to determine whether this had an impact on overall survival (OS). Methods: In this retrospective, single-center study, all adult patients diagnosed with AML from August 2016–December 2017 were reviewed. Baseline characteristics, somatic mutations in the diagnostic bone marrow as detected by Next Generation Sequencing (NGS), and survival outcomes were analyzed. NGS panel was done in-house and could identify 94 genes. Patients were divided into favorable, intermediate, and poor risk groups based on cytogenetics, and molecular abnormalities using NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML, version 1.2018. Kaplan-Meier plots and Cox regression analyses were utilized. Results: A total of 105 AML patients were included; baseline characteristics and frequency of identified clinically significant (CS) mutations are described in the presentation. The FLT3 mutation occurred in the highest frequency (22%) followed by DNMT3A & ASXL1 (15%). 17 (16%) patients were favorable risk, 33 (31%) intermediate risk, and 55 (52%) were poor risk. 67.6% of patients were male, and the median age was 64 (20–79) years. There was a difference in the number of CS mutations between the intermediate risk group and favorable risk group (P=.007), but not between the favorable risk and poor risk groups (P=.221) or between the intermediate risk group and poor risk group (P=.093). Increased number of CS mutations (≥ 5) was seen with equal frequency across risk groups and predicted for shorter overall survival in both univariate (HR=2.80; P=.039) and by multivariate Cox regression analysis (P=.001) independently from assigned risk group. There were no differences in age, gender, smoke, geographic, and different risk groups by multivariate analyses. Conclusion: Our study shows that ≥ 5clinically significant somatic mutations were associated with adverse outcomes and decreased survival, independent of risk groups and induction regimen. Thus, it may be a useful prognostic factor. This finding needs to be validated using a larger sample size.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

Cytoreductive nephrectomy (CN) in metastatic renal cancer (mRCC): Update on Carmena trial with focus on intermediate IMDC-risk population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4508-4508 ◽  
Author(s):  
Arnaud Mejean ◽  
Simon Thezenas ◽  
Christine Chevreau ◽  
Karim Bensalah ◽  
Lionnel Geoffrois ◽  
...  
Keyword(s):  
Risk Factor ◽  
Risk Group ◽  
Risk Groups ◽  
Phase Iii ◽  
Intermediate Risk ◽  
Metastatic Renal Cancer ◽  
Phase Iii Trial ◽  
Metastatic Site ◽  
Trial Testing ◽  
Metastatic Sites

4508 Background: Carmena was a randomized phase III trial, testing the benefit of CN followed by sunitinib (arm A) vs sunitinib alone (arm B), with stratification by MSKCC risk groups in 450 mRCC patients. Based on this trial, CN is not anymore recommended in mRCC (NEJM, Mejean et al, 2018). However there are questions about which patients could still benefit from CN, especially in intermediate risk group. In the present study, we investigated different subgroups from the Carmena trial to answer these questions. Methods: Carmena trial was initially stratified according to MSKCC risk groups. For the purpose of this analysis, we reclassified the patients based on IMDC risk groups. We also analyzed patients with one metastatic site vs more than one, as well as patients with secondary nephrectomy in arm B. Overall survival (OS) was the primary endpoint. Results: With a updated median FU of 61.5 months (mo), the median OS by ITT analysis was 15.6 vs 19.8 mo in arm A and B respectively stratified on MSKCC (HR 0.933 ; 95% CI [0.76- 1.15]) / stratified on IMDC (HR 0.957 ; 95% CI [0.78- 1.18]). Using IMDC risk group factors, 58.6% patients were intermediate and 41.4 % were poor risk. When looking at intermediate risk group only, 48.1% had only one risk factor (interval between diagnosis and treatment < 1y), with a median OS of 30.5 and 25.2 mo in arm A and B respectively (HR 1.24 [0.81 – 1.90]). By contrast, 51.9 % had two risk factors (mostly low hemoglobin, high corrected calcium or neutrophils), with a median OS of 16.6 and 31.2 mo in arm A and B respectively (HR 0.61 [0.41 – 0.91] p = 0.015). Regarding number of metastatic sites, 33% had only one metastatic site. Median OS was 23.6 and 22.7 mo in arm A and B respectively (HR 1.08 [0.75 – 1.57]. Finally, 40 patients had a secondary nephrectomy in arm B, with median OS of 48.5 mo [CI 95%: 27.9-64.4] vs 15.7 mo [CI 95%: 13.3-20.5] in patients who never had surgery. Conclusions: With longer FU, Carmena trial confirms that CN is not superior to sunitinib alone in ITT population, both with MSKCC and IMDC risk groups. However for patients with only one IMDC risk factor, CN might be beneficial. Number of metastatic site is not helpful to define good candidates for surgery. Finally, patients with secondary nephrectomy have very long OS, supporting this strategy. Clinical trial information: NCT00930033.

Palliative prognostic tools for the terminally ill patients with gastric cancer.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 120-120 ◽  
Author(s):  
Beodeul Kang ◽  
Hye Jin Choi ◽  
Sun Young Rha
Keyword(s):  
Gastric Cancer ◽  
Survival Time ◽  
Cancer Patients ◽  
Risk Group ◽  
Terminally Ill ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Poor Risk ◽  
Gastric Cancer Patients

120 Background: Terminally ill patients with gastric cancer have specific gastrointestional symptoms and signs related with cancer progression. To estimate accurate survival expectancy of gastric cancer patients is important for timely decision making of their end of life issues. Methods: We reviewed the 276 patients with terminally ill gastric cancer who were treated at Yonsei Cancer Center between January 2007 and December 2011 and eventually were died. Retrospectively, we conducted the data of clinical signs, symptoms, and laboratory results at the time of cessation of the active treatment. Then, we established the palliative survival estimation model by stratification of risk group. Results: Median palliative survival time from the decision to stop further treatment to death was 42days. In the multivariate Cox regression analysis, 5 parameters were identified as prognostically significant factors: anorexia, dyspnea, hypoalbuminemia, elevated blood urea nitrogen, and elevated serum alkaline phosphatase. We scored each variables as 1-3 for symptom(1:asymptomatic, 2:symptomatic, 3:symptomatic requiring intervention) and 1-2 for lab results(1:normal, 2:abnormal) and summed up each scores. Using the total score, patients were divided into 3 risk groups: low-risk(5-7points), intermediate-risk(8-11points), and poor-risk patients(12point). As a result, median palliative survival for low-risk group(n=110) was 87.0±7.4days, intermediate-risk group(n=158) and poor-risk group(n=8) were 31.0±2.1days and 6.0±2.1days, respectively (p<0.0001). Conclusions: Using multivariate analysis and summation of each prognostic factor score, 3 risk groups were determined. After validation by prospective multicenter trial, this palliative survival time estimation tool will be helpful to inform the accurate survival for terminally ill gastric cancer patients.

Clinical relevance of high–intermediate risk endometrial cancer according to European risk classification

2020 ◽  
Vol 30 (10) ◽  
pp. 1528-1534
Author(s):  
Agnieszka Rychlik ◽  
Ignacio Zapardiel ◽  
Laura Baquedano ◽  
María Ángeles Martínez Maestre ◽  
Denis Querleu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
European Society ◽  
Risk Group ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Nodal Metastases ◽  
Disease Free

ObjectiveRisk models in endometrial cancer define prognosis and indicate adjuvant therapy. One of the currently used classifications was designed in 2016 in collaboration with the European Society of Medical Oncology (ESMO), the European Society of Gynecologic Oncology (ESGO), and the European Society of Radiotherapy (ESTRO). A high–intermediate risk group was introduced within the intermediate risk group. The purpose of this study was to evaluate the clinical relevance of this subclassification.MethodsA multicenter retrospective study was carried out at five international tertiary institutions. Patients diagnosed with intermediate risk endometrial cancer on the basis of definitive pathology findings were included. Patients were stratified into intermediate and high–intermediate risk groups. Incidence of nodal metastases, and disease free and overall survival were compared between the two risk groups in univariate and multivariate analysis.Results477 patients were included: 325 (68%) patients were identified as intermediate and 152 (32%) as high–intermediate endometrial cancer patients. Nodal metastases were found in 18 patients (11.8%) in the high–intermediate risk endometrial cancer group and 16 patients (4.9%) in the intermediate risk group. Lymphovascular space invasion was found to be a strong predictive factor of lymph node involvement. High–intermediate risk was found to be an independent factor of disease free survival (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00 to 3.08; p=0.050) and overall survival (HR 1.99; 95% CI 1.10 to 3.60; p=0.022) in the multivariate analysis.ConclusionsThe study validates the clinical significance of the intermediate risk endometrial cancer subclassification. Prognosis for high–intermediate risk endometrial cancer was significantly poorer. The prevalence of lymph node metastases was higher in this group of patients.

Cytogenetic Classification Systems and Overall Survival Following Bone Marrow Transplant (BMT) for Acute Myelogenous Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4500-4500
Author(s):  
Matt Kalaycio ◽  
Mikkael Sekeres ◽  
Ronald Sobecks ◽  
Lisa Rybicki ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Classification Systems ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Intermediate Risk ◽  
Poor Risk ◽  
First Complete Remission

Abstract Risk-adapted therapy for AML in first complete remission generally calls for allogeneic BMT for patients with poor risk cytogenetics. However, poor risk cytogenetics is defined differently in commonly-applied classification schemes. We hypothesized that differences in cytogenetic classification might result in differences in survival after BMT. From September 1991 to December 2003, we treated 47 patients with AML in first complete remission with high-dose busulfan-containing preparative regimens and an HLA-matched sibling BMT. The median age was 42 years (range 18 to 60). At the time of diagnosis, 35 patients had either a normal karyotype or at least one clonal abnormality. Cytogenetic analysis was unavailable for the other 12 patients. The 47 patients were then classified according to the SWOG/ECOG (Blood96:4075, 2000), MRC (Blood92:2322, 1998), or CALGB (Blood100:4325, 2002) cytogenetic classification systems and analyzed for overall survival. With a median follow-up of 4.9 years, 3 year overall survival for various cytogenetic risk groups are displayed in the table: SWOG/ECOG CALGB MRC Intermediate risk 69% 63% 74% Poor risk 43% 42% 18% Unknown risk 45% 52% 45% Concordance indices were 0.58 for CALGB, 0.60 for SWOG, and 0.66 for MRC, demonstrating a slight superiority of the MRC system. Consistent with reports of large, prospective randomized trials of BMT for AML in first remission, patients with poor risk cytogenetics have worse overall survival compared to patients with intermediate risk cytogenetics. Overall survival appears to be different for patients classified as poor risk by MRC criteria. Larger, prospective studies are needed to confirm this observation, but our results suggest that standardized, international cytogenetic risk criteria are needed to develop risk-adapted strategies for the treatment of AML.

Validation of the Newly Proposed MD Anderson Prognostic Risk Model for Patients with Myelodysplastic Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 444-444
Author(s):  
Maria Corrales-Yepez ◽  
Jeffrey E. Lancet ◽  
Alan F. List ◽  
Mohamed A. Kharfan-Dabaja ◽  
Teresa Field ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Kaplan Meier ◽  
Md Anderson

Abstract Abstract 444 Background: The international prognostic scoring system (IPSS) is the most widely used clinical tool for risk stratification and tailoring treatment in myelodysplastic syndromes (MDS). Despite its utility, the IPSS has several limitations. The IPSS was developed using outcomes of untreated primary MDS patients at time of diagnosis, and does not account for patient age, performance, and degree of cytopenia. The recently reported MD Anderson risk model (MDAS) addresses many of the limitations of IPSS (Kantarjian et al, CANCER September 15, 2008 / Volume 113 / Number 6). We validated this new risk model in a large external single institution cohort of patients. Methods: Data were collected retrospectively from Moffitt Cancer Center (MCC) MDS database and chart review of patients with MDS. The primary objective was to validate the new risk model calculated at time of initial presentation MCC. The MDAS was calculated as published based on age, performance status, blast%, degree of thrombocytopenia, cytogenetics, white blood cell count, and prior history if transfusion. Patients were divided into four risk groups: low (0-4 points), int-1 (5-6 points), int-2 (7-8 points), and high risk (≥ 9 points). All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 844 patients were captured by MCC MDS database. The median age was 69 years, MDS subtypes were coded as Refractory anemia (RA) 98 (12%), refractory anemia with ring sideroblasts (RARS) 76 (9%), MDS with del(5q) 20 (2.4%), refractory cytopenia with multi-lineage dysplasia (RCMD) 96 (11%), refractory anemia with excess blasts (RAEB) 255 (30%), therapy related MDS 22 (2.6%), and MDS-nos 275 (33%). IPSS risk groups were low risk in 158 (18.7%), intermediate-1 (int-1) 362 (42.9%), intermediate-2 (int-2) 168 (19.9%), high risk 45 (5.3%), and missing in 111 (13.2%). Based on the new risk model 169 patients (20%) were low risk, 250 (29.6%) int-1, 182 (21.6%) int-2, 135 (16%) high risk, and 94 (11.1%) were unknown. The median OS for all patients was 36 months (95% CI 31.5–40.5 mo). Age, IPSS risk group, serum ferritin, and RBC transfusion dependence were all significant prognostic factors in univariable analysis. The median OS was 92 mo (95%CI 68.1–115.9 mo), 49 mo (95%CI 40.4–57.6 mo), 26 mo (95%CI 21.2–30.8 mo), and 15 month (95%CI 11.8–42.1 mo) respectively for patients with low, int-1, int-2 and high risk patients according to MDAS. (Figure-1) (P < 0.005). In patients with low/int-1 IPSS risk group the median OS according to MDAS was 92 mo (95%CI 68.3–115.7 mo), 49 mo (95%CI 49.3–58.7 mo), 28 mo (95%CI 20.7–35.3), and 19 mo(95% CI 9.9–28.1 mo) respectively for patients with low, int-1, int-2, high risk MDAS (p<0.005). In patients with int-2/high IPSS risk categories only 4 patients were reclassified as low MDAS risk and the median OS for those patients was 10 month (95% CI 0–38 mo). The median OS was 49 mo (95%CI 23.5–74.5 mo), 23 mo (95%CI 19.4–26.6 mo), 14 mo (95% CI 11.5–16.5 mo). (p<0.005). For all the patients the rate of AML transformation according to MDAS was 5.9%, 16.8%, 36.3%, and 50.4% respectively for low, int-1, int-2, and high risk MDAS groups. (p <0.005). In Cox regression analysis, higher risk MDAS predicted inferior OS (Hazard ratio (HR) 1.54 (95%CI 1.35–1.75) (p <0.005) independent of IPSS risk group (HR 1.25 95%CI 1.1–1.45) (p =0.004). Conclusion: Our data validates the prognostic value of the MDAS risk model which was predictive for overall survival and AML transformation. The MDAS complements the IPSS particularly in low/int-1 risk group by identifying patients with higher risk disease behavior and inferior outcome. The utility of this model as a treatment decision tool should be studied prospectively. Disclosures: No relevant conflicts of interest to declare.

An FDA-pooled analysis of frontline combination treatment benefits by risk groups in metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4559-4559
Author(s):  
Daniel Lee ◽  
Haley Gittleman ◽  
Chana Weinstock ◽  
Daniel L. Suzman ◽  
Erik Bloomquist ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Risk Model ◽  
Risk Group ◽  
Risk Groups ◽  
Pooled Analysis ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Poor Risk ◽  
Anti Vegf ◽  
Line Setting

4559 Background: The International Metastatic RCC Database Consortium (IMDC) risk model was developed for prognosis of patients with mRCC treated with vascular endothelial growth factor (VEGF)-targeted monotherapy in the first-line setting. Efficacy in trials of anti-VEGF therapy has been generally consistent across risk groups, including for overall survival (OS). For trials of immunotherapy combinations, the small numbers of OS events for the favorable risk group in each trial limited reliable conclusions; however, there was a suggestion of possible differential effects on OS between favorable risk and other risk groups. Methods: We pooled individual patient data (n=3447) from four phase III randomized trials of combinations of immunotherapy + immunotherapy (n=1) or immunotherapy + anti-VEGF therapy (n=3) submitted to the US Food and Drug Administration in support of marketing applications. All trials calculated IMDC risk group for each patient and used a control arm of sunitinib. We combined intermediate and poor prognostic groups (“intermediate/poor”) and compared their OS to that of the favorable risk group using Kaplan-Meier and Cox Proportional Hazards methods. Results: In this pooled analysis, treatment with combination immune checkpoint therapy did not demonstrate an improvement in OS compared to sunitinib in the favorable risk group (HR 0.953; 95% CI: 0.72, 1.27). An improvement in OS was observed in the intermediate/poor risk group (HR 0.696; 95% CI: 0.62, 0.78). Conclusions: Our analysis of OS in patients treated with immunotherapy combinations compared to sunitinib suggests possible differential benefit in the favorable risk compared to the intermediate/poor risk group. These results are not conclusive and considered exploratory due to the relative immaturity of OS in the favorable risk group. Follow-up for survival continues in each study to allow for more definitive results.[Table: see text]

scholarly journals The Impact of Cytogenetics on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Survey from the Acute Leukemia Working Party (ALWP) of EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4639-4639
Author(s):  
Monica Poiani ◽  
Myriam Labopin ◽  
Dietrich W. Beelen ◽  
Johanna Tischer ◽  
Jürgen Finke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Stem Cell Transplantation ◽  
Research Funding ◽  
Risk Group ◽  
Chronic Gvhd ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Free Survival

Abstract Introduction: Diagnostic karyotype is one of the most important determinants of initial response to treatment, remission duration and overall survival in Acute Myelogenous Leukemia (AML). Moreover, risk stratification of AML based on cytogenetic abnormalities is a key parameter for the success rate and outcome of allogeneic stem cell transplantation (allo-SCT) in AML. However, while the prognostic significance of chromosomal abnormalities is well established during frontline therapy, its influence at time of salvage therapy in Primary Refractory (Ref) and Relapsed (Rel) AML and the role of allo-SCT in this subset, remains uncertain. Patients and methods: This was a survey from the EBMT registry which included adult AML patients undergoing allo-SCT for Ref/Rel AML from HLA-matched related or 9/10 - 10/10 unrelated donor (UD) between 2000 and 2017. Patients were stratified according to cytogenetic risk as defined by Grimwade et al. (Blood 2010). Primary endpoint was Leukemia-Free Survival (LFS). Secondary endpoints were relapse cumulative incidence (RI), non-relapse mortality (NRM), overall survival (OS), acute and chronic GVHD and GVHD-relapse-free Survival (GRFS). Results: 2089 patients with Ref AML (n=972) and Rel AML (n=1117) were analyzed: 154 patients had a favorable risk, 1283 were in intermediate risk and 652 had an adverse cytogenetic risk. Median follow-up was 49 months. Patients and transplant characteristics are summarized in table 1. Patients in the favorable risk group were younger and transplanted more frequently in first or second relapse. Patients in the adverse risk group received more frequently transplants from 9/10 UD. FLT3-ITD mutation was present in 18%, 43% and 16% of the favorable, intermediate and adverse risk groups, respectively (p<10-3). The 3 groups were not significantly different in terms of Karnosfky score, patient and CMV serology status and conditioning intensity (myeloablative or reduced). Outcome correlated with cytogenetic category, with a percentage of complete remission within 100 days after transplant of 79%, 69% and 61% (p<10-3), RI at 2 years were 42%, 51% and 61% (p<10-5), LFS and OS rates were 34%, 27%, 18% and 41%, 33%, 22% in favorable, intermediate and adverse risk group (p<10-5 for both LFS and OS), respectively. Non-relapse mortality, on the contrary, did not differ among the three groups (24%, 21% and 21%, respectively; p=NS). We performed a multivariate analysis adjusting for all factors differing between risk groups and factors known as influencing outcome of AML patients after allograft. Compared to the favorable risk group, intermediate risk group was associated with a higher RI (HR=1.58; 95% CI: 1.17-2.14; p=0.003), lower LFS (HR=1.39; 95% CI: 1.09-1.77; p=0.008), lower OS (HR=1;47; 95% CI: 1.14-1.90; p=0.003) and lower GRFS (HR=1;29; 95% CI: 1.03-1.61; p=0.03). The adverse risk group was associated with a higher RI (HR=2.27; 95% CI: 1.65-3.10; p<10-5), lower LFS (HR=1.86; 95% CI: 1.44-2.40; p<10-5), lower OS (HR=1.89; 95% CI: 1.44-2.47; p<10-5) and lower GRFS (HR=1.62; 95% CI: 1.28-2.06; p<10-4; Figure1). In a subgroup analysis of patients in intermediate or adverse risk groups with available information on FLT3-ITD status, adverse cytogenetics remained an important prognostic factor for RI (HR=1.55; 95% CI: 1.22-1.97; p=0.0004), LFS (HR=1.37; 95% CI: 1.12-1.68; p=0.002), OS (HR=1.38; 95% CI: 1.11-1.70; p=0.003) and GRFS (HR=1.31; 95% CI: 1.08-1.59; p=0.006) compared to the intermediate risk group. Other poor prognostic factors in this population were presence of FLT3-ITD mutation, Rel vs Ref status at transplant, Karnofsky score <80%, use of bone marrow as stem cell source and patient CMV serology positivity. In vivo T cell depletion was associated with a lower risk of acute and chronic GVHD and a better GRFS. Conclusion: In Rel and Ref AML karyotype remains an important prognostic factor for those patients undergoing allo-SCT in active disease phase, allowing to separate patients into different risk groups. Moreover, FLT3-ITD mutation remains a negative prognostic factor in this population. Disclosures Beelen: Medac: Consultancy, Other: Travel Support. Tischer:Jazz Pharmaceuticals: Other: Jazz Advisory Board. Finke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Mohty:MaaT Pharma: Consultancy, Honoraria.

Identification of Eight Surface Molecules with Survival Predictive Power in B Cell Chronic Lymphocytic Leukemia (B-CLL): A Proposal for a Scoring System.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2797-2797
Author(s):  
Valter Gattei ◽  
Paolo Sonego ◽  
Stefania Russo ◽  
Riccardo Bomben ◽  
Michele Dal Bo ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Predictive Power ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Z Score ◽  
Surface Molecules

Abstract Studies of gene expression profiling of B-CLL cells revealed a phenotype related to experienced B cells, although only a subset of B-CLLs has IgVH mutations. With the aim to identify the immunophenotypic profile associated with a different prognosis, we investigated by flow cytometry the expression of 36 surface molecules (cell-adhesion molecules, integrins, complement activity regulators, myeloid, T and B markers) in 125 B-CLLs, all characterized for IgVH mutations and survival. To recognize the surface molecules with survival predictive power, univariate Cox proportional-hazards analysis was applied to antigen expression values with overall survival as dependent variable. Once identified the antigens whose expression correlated with a z score of ±2.5 (P&lt;0.005) or greater, the maximally selected log-rank statistics were applied to define the optimal cut-off values yielding the best separation of two subgroups with different survival. According to this approach, the following eight antigens were selected (cut-off values in parenthesis): CD55 (30%), CD62L (30%), CD49c (40%), CD11c (20%), CD54 (50%), CD25 (15%), CD79b (65%), CD38 (30%). The first six antigens had negative z score and therefore were identified as favorable prognosticators, while CD79b and CD38 had positive z score, hence were associated with shorter overall survival (negative prognosticators). To build-up a scoring system, we assigned score “1” to each positive prognosticator when its expression was above the designated cut-off (score “0” if below), and score “0” to each negative prognosticator when its expression was above the cut-off (score “1” if below). A total score ranging from 0 to 8 points was therefore obtained in 102/125 cases in which the expression of all the eight markers was available. Three risk groups were identified: i) high-risk (29 cases), score 0–3; ii) intermediate-risk (38 cases), score 4–6; iii) low-risk (35 cases), score 7–8. These three groups differed greatly for survival probabilities (p=5x10–13 by the log-rank test). All patients belonging to the low-risk group were alive throughout the follow-up duration, whereas mean survivals for intermediate- and high-risk groups were 173 months (p=0.032) and 61 months (p=2.0x10–9), respectively. Several relationship between risk groups and other variables was studied: i) patients included in high- and intermediate-risk groups had the same male to female (M:F) ratio (1.4), while the M:F ratio of patients included in low-risk group (group 3) was lower (0.7); ii) Rai’s stage distribution was comparable in the three groups, with the exception of stage “0”, which was significantly less frequent in the high-risk group (p=0.04); iii) if % IgVH mutations (2% cut-off) was checked, mutated to unmutated (M:UM) ratios were 4.8, 2.6 and 0.8 in low-, intermediate- and high-risk groups, respectively (p=0.006); iv) as compared to high-risk group, low- and intermediate-risk groups were characterized by a higher number of B-CLL cases with a IgVH mutational status consistent with antigen-driven selection (20/24 and 17/26 vs. 7/13). In conclusion, the present study introduces a novel predictive tool based on the expression of eight surface molecules, easily investigable, which can stratifies populations of B-CLL patients in three distinct risk categories.

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