Application of the French prognostic score (FPS) to assess overall survival (OS) in a U.S.-based cohort of patients (pts) treated with azacitidine (Aza).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7126-7126
Author(s):  
Amer Zeidan ◽  
Zhuoxin Sun ◽  
Thomas Prebet ◽  
Peter Greenberg ◽  
Mark Juckett ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Model ◽  
Prognostic Score ◽  
Performance Status ◽  
Risk Groups ◽  
Therapeutic Interventions ◽  
Rank Test ◽  
Clinical Criteria ◽  
Entire Cohort

7126 Background: In pts with IPSS high-risk myelodysplastic syndrome (HR-MDS), Aza prolonged OS. The FPS was developed for Aza-treated HR-MDS pts based on 4 baseline clinical criteria: Performance status, karyotype, presence of circulating blasts, and RBC transfusion dependency (TD) (Itzykson et al, Blood 2011). The FPS discriminated 3 risk groups [low-risk [LR), intermediate-risk (IR), and high-risk (HR), with significantly different median OS at 32, 15, and 6 months (M), respectively. We sought to validate the FPS in a U.S.-based cohort. Methods: The North American Leukemia Intergroup Trial E1905 randomized 150 pts with MDS, CMML, and AML with dysplastic changes to Aza 50 mg/m2/day (d) for 10 d +/- entinostat (Ent) 4 mg/m2/d on d3 and d10. OS was defined as time from registration to death from any cause, with follow-up censored at last contact. Kaplan-Meier estimates were used for survival distribution. Results: The FPS could be determined for 115 pts. Median follow-up was 48.5 M. The median OS was significantly different between the HR, IR, and LR FPS groups in the 115 pts (9.7, 14.7, 25.3 M, respectively, log Rank test P=0.017), and for pts in Aza arm (n=55) (7.8, 19.3, 26.4 M, respectively, P=0.008), but not for patients in the Aza+Ent arm (n=60) (12.5, 12.4, 24.1 M, respectively, P=0.21). Using multivariate Cox model with WBC count, hemoglobin, disease type, and platelet TD, the prognostic effect of HR vs. LR FPS groups remained significant for the entire cohort (P=0.046) and for the Aza arm (P=0.037). No significant differences in response rates were observed. Conclusions: The FPS warrants further evaluation as a baseline prognostic tool that can define a subgroup of pts with lower probabilities of achieving survival benefit from Aza therapy. Such pts might be considered from alternative therapeutic interventions.

A New Molecular and Clinical Prognostic Score for Risk Stratification in CN-AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2635-2635
Author(s):  
Friederike Schneider ◽  
Annika Dufour ◽  
Tobias Benthaus ◽  
Stephanie Schneider ◽  
Gudrun Mellert ◽  
...  
Keyword(s):  
Platelet Count ◽  
De Novo ◽  
Prognostic Score ◽  
Performance Status ◽  
Risk Groups ◽  
Wild Type ◽  
Free Survival ◽  
De Novo Aml ◽  
Definition Of

Abstract Abstract 2635 Poster Board II-611 Background: Cytogenetically normal acute myeloid leukemia (CN-AML) is associated with an intermediate outcome. A number of clinical and molecular risk factors have been characterized pointing to the heterogeneity of this group. The purpose of the study was to define a prognostic model based on pre-treatment patient characteristics to facilitate choice of therapy by definition of patient groups with different prognoses. Patients and methods: We evaluated four molecular markers (mutations of NPM1, CEBPA, MLL-PTD; FLT3-ITD mutant level; interaction term NPM1 and FLT3-ITD mutant level) and nine clinical parameters (white blood count (WBC), platelet count, hemoglobin level, lactase dehydrogenase (LDH) level, bone marrow blasts, de novo AML vs. non de novo AML, performance status, sex and age) at initial diagnosis in 648 patients with CN-AML treated in the AMLCG (German AML Cooperative Group) 1999 trial. The outcome parameter overall survival (OS) was calculated from randomization to death from any cause or to the latest follow-up date. Event-free survival (EFS) was defined as the period from the start of therapy until lack of a complete remission (CR), relapse of AML after CR or death without relapse. Relapse-free survival (RFS) was determined for responders from the first day of a CR until relapse or death without relapse. Univariate and multivariate Cox regression analyses for OS were performed. All parameters with p'0.05 in multivariate analyses after backward elimination and their regression coefficients were applied in the prognostic score. The minimal p-value approach was used to identify the risk groups with the greatest differences in OS. Results: In our patient cohort 84% had de novo AML. Median age was 60 years (17–85 years) and 70% had an ECOG score ≤1. Median platelet count was 57 G/l (5–643 G/l), median WBC was 18 G/l (0.1–798 G/l) and median hemoglobin level was 9.2 g/dl (4.2–16.4 g/dl). Mutations of NPM1, FLT3-ITD, MLL-PTD and CEBPA were present in 51%, 27%, 8% and 10% of patients, respectively. Median FLT3-ITD mutant level in FLT3-ITD mutated patients was 0.42 (0.02–1.00). Of 648 patients 377 had died. Median OS was 20 months with a median follow-up of 45 months. In the multivariate analyses for OS, the following parameters were significant: age (+10, years, HR: 1.3, p<0.001), WBC (10 fold, ×109/l, HR: 1.4, p<0.001), NPM1 (mutation vs. wild-type, HR: 0.35, p<0.001), CEBPA (mutation vs. wild-type, HR: 0.47, p=0.001), interaction term NPM1/FLT3-ITD mutant level (+1, HR: 4.5, p=0.006), performance status (ECOG 0,1 vs. ECOG 2-4, HR: 1.4, p=0.006) and platelet count (10 fold, ×109/l, HR: 0.70, p=0.016). After calculation of the prognostic score for each patient and definition of two cutpoints, we could identify three risk groups (median OS (N=590): not reached (n=169) vs. 22.7 months (n=220) vs. 8.4 months (n=201), p<0.001; median EFS (N=583): 42.3 months (n=168) vs. 7.6 months (n=216) vs. 3.2 months (n=199), p<0.001; median RFS (N=383): not reached (n=136) vs. 15.3 months (n=143) vs. 7.6 months (n=104), p<0.001). Furthermore this model was valid in both age subgroups (<60 years / ≥60 years). Interestingly, a subset of 31% of patients within the molecular favorable NPM1+/FLT3-ITD- risk group were assigned to the intermediate group according to our prognostic score and 31% of the low risk group were not NPM1+/FLT3-ITD-. Conclusions: We propose a new prognostic score based on pre-therapeutic clinical and well-established molecular markers that could be easily applied in the routine patient care setting for risk stratification and risk-adapted therapy. Further prospective validation is required to confirm the clinical relevance of this score. Disclosures: Unterhalt: Roche: travel support. Hoster:Roche: travel support.

scholarly journals P105 PREVENTION OF INCISIONAL HERNIA WITH A REINFORCED TENSION LINE (RTL) VS PRIMARY SUTURE ONLY IN MIDLINE LAPAROTOMIES: 3 YEARS FOLLOW UP

2021 ◽  
Vol 108 (Supplement_8) ◽  
Author(s):  
Edgard Efren Lozada Hernandez ◽  
Elizabeth Escamilla Chavez ◽  
Leticia Hernandez Villegas
Keyword(s):  
High Risk ◽  
Incisional Hernia ◽  
Cox Regression ◽  
Risk Groups ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Number Needed To Treat ◽  
Primary Suture ◽  
Midline Laparotomy

Abstract Aim “Incisional hernia (IH) has an incidence of 10–23%, which can increase to 38% in specific risk groups. The objective of this study is to report the results at 3 years of follow-up of the use of the reinforced tension line (RTL) technique compared with primary suture only (PSO) closure in the prevention of IH in high-risk patients undergoing laparotomy.” Material and Methods “Open randomized controlled clinical trial. Included were patients older than 18 years who underwent midline laparotomy, emergency or scheduled, who were considered high risk, and who completed 3-year follow-up. The patients were randomized 1:1 to the RTL technique or to PSO. The objective was to report the incidence of IH and the complications associated with the closure method. Intention-to-treat analysis and Cox regression were performed.” Results “A total of 124 patients were randomized; 51 patients from the RTL group and 53 patients from the PSO group finished the 3-year follow-up. The incidence of IH was higher in the PSO group (15/53, 28.3%) than the RTL group (5/51, 9.8%) (p = 0.016, OR 0.35, 95% CI 0.14–0.88, number needed to treat 5.4, log-rank test p = 0.017). The groups were similar in the rates of surgical site infection, hematoma, seroma, and postoperative pain during follow-up.” Conclusions “The RTL technique is useful in the prevention of IH when compared with PSO in high-risk midline laparotomy patients, and it is not associated with a higher percentage of complications. Clinical trials NCT02136628, retrospectively registered”

Combined overexpression of WT1 and BAALC genes May Predict AML evolution in MDS Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5204-5204
Author(s):  
Daniele Avenoso ◽  
Enrico De Astis ◽  
Nicoletta Colombo ◽  
Raffaella Grasso ◽  
Micaela Bergamaschi ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Prognostic Score ◽  
Risk Groups ◽  
Disease Diagnosis ◽  
Low Risk ◽  
Risk Category ◽  
Copy Numbers ◽  
Combined Overexpression

Abstract Background and aims Myelodisplastic syndromes (MDS) are a group of hemopoietic disorder characterized by an impaired blood cell production, morphologic dysplasia and peripheral cytopenias; they are the most common hematologic neoplastic disorder and its diagnosis relays on morphologic evaluation, associated to a karyotypic assay. In order to predict the outcome of patients affected from these disorders, knowing that the order of survival can be extremely variable, several prognostic index were developed such as International Prognostic Score Sistem (IPSS) or the most usefull WHO-Prognostic Score Sistem (WPSS). On the contrary of acute leukemia, these disorders have not a biomolecular profile evalutation of intrinsic markers able to stratify patients in different prognostic risk groups. The aim of our study is to assess the risk of leukemic evolution, in MDS patients, on the basis of the levels expression of WT1 and BAALC at disease diagnosis, and to evaluate the leukemia free survival (LFS) at 6-12-24-36 months of follow up, among the different risk category according to IPSS and irrespectively of treatment. Materials and method In five years we analized 102 patients with a diagnosis of MDS divided according to the WHO classification such as follows: 38 AR, 1 AR with del(q5), 21 aREB-1, 23 AREB-2, 3 chronic myelomonocitic leukemia, 1 RARS, 1 MDS, 11 RCMD, 1 5q- syndrome, 2 suspected MDS. According to IPSS 58 belonged to the low risk category, 21 to the intermediate-1, 23 to the intermediate-2/high risk. Cytogenetic assay showed 20 people with an abnormal karyotype, 8 of them fallen into the high risk class and 12 into the intemediate risk. Low risk and intermediate-1 patients were treated only with supportive care; high risk patients were treated with hypomethylating agents. Iron chelation were used when necessary. Lenalidomide was used in the only case of 5 q- syndrome Samples of bone marrow were analized with Real-Time quantitave PCR and levels of WT1 and BAALC expression were determinated. Molecular datas were analized with X-square Test and a significant association was recorded between overexpression of the genes evaluated (WT1 higher than 100 copy numbers and BAALC higher than 1000 copy numbers) and the probability of develop acute myeloid leukemia ( AML ). Results Nine out of 102 patients showed an isolated WT1 hyperexpression (3 of them developed an AML ), in 15 cases we reported an isolated BAALC overexpression (3 of them developed an AML ), while 13 out 18 patients ( 72% ) with combined WT1 and BAALC overexpression developed AML within an average time of 6 months; instead only 5% of patients, which expressed low levels of WT1 and BAALC, developed AML within the interval of observation. In particulary a combined high expression of WT1 and BAALC were strongly associated with an high risk to develop leukemia and a short LFS, especially in INT-1 subset. After that we calculated the LFS, divided for the risk category at 6-12-24-36 months of follow up. Patients with combined overexpression of WT1 and BAALC showed a LFS of 40% at 6 months of follow up and 0% at 24 months. Conclusion MDS have a great variable survival, and the current approach to these diseases relays on morphological evaluation, karyotypic assay and need of transfusional support; gene expression could be a promising system to predict the prognosis in these patients. Analysis of gene expression, which belong to AML evaluation, allows to divide patients in several risk groups; furthermore is not the single gene evaluation that is more predictable but a combined assay. With this method, which seems to be more realiable than IPSS, we could find that a great percentage of patients with levels of WT1>100 and BAALC >1000, indipendently from karyotypic status and treatment, developed AML and have a shorter LFS than the population with WT1 <100 and BAALC < 1000. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Oncological results of neoadjuvant chemohormonal therapy in patients with high and very high-risk prostate cancer

2020 ◽  
Vol 16 (1) ◽  
pp. 54-63
Author(s):  
M. V. Berkut ◽  
A. S. Artemjeva ◽  
S. A. Reva ◽  
S. S. Tolmachev ◽  
S. B. Petrov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Specific Antigen ◽  
Risk Groups ◽  
Rank Test ◽  
Chemohormonal Therapy ◽  
Log Rank Test ◽  
Oncological Results ◽  
Very High

Tolsotogo St., Saint Petersburg 197022, RussiaBackground. Prostate cancer (PCa) of a high and very high risk is a potentially fatal disease that requires an active multimodal approach, including the use of neoadjuvant drug treatment. As option for this treatment is neoadjuvant chemohormonal therapy (NCHT) followed by radical prostatectomy (RPE). However, data on the oncological results of treatment of such patients are still limited and the role of neoadjuvant therapy in the treatment of high and very high-risk PCa remains not fully understood.Objective: to assess the oncological results of treatment patients with localized and locally advanced PCa of high and very high risk after NCHT. Materials and methods. This was a prospective randomized study: patients with PCa of high and very high-risk groups (prostate specific antigen levels (PSA) >20 ng/ml and/or Gleason score ³8 and/or clinical stage >T2c) were treated with RPE only (group RPE; n = 35) or NCHT followed by RPE (NCHT/RPE group; n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6 subcutaneous injections every 28 days). After a follow-up examination evaluating the result of the neoadjuvant regimen, patients underwent RPE with extanded lymphadenectomy.Results. A mean follow-up was 37.08 ± 20.46 months. A statistically significant reduction of prostate specific antigen >50 % post-chemohormonal therapy was observed in all 36 cases. Lower postoperative stage was noticed in 38.5 % in NCHT/RPE group compared with 2.7 % in RPE group. Similarly, positive surgical margin rate was higher in group without neoadjuvant therapy – 40 and 25 % (RPE group). Cancerspecific survival was 97.2 % in NCHT/RPE group and 87.56 % in the RP group (p = 0.037), cancer specific survival rate – 91.4 % and 97.2 % respectively (log-rank test p = 0.22). At the same time, no statistically significant differences were obtained in 3-year recurrence free survival between groups: 38.8 % in NCHT/RPE group versus 43.6 % in the RPE group (log-rank test p = 0.36).Conclusion. Conducting NCHT before RPE is a safe and effective strategy in patients with PCa of high and very high risk groups and could improve oncological results.

scholarly journals The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 671
Author(s):  
Margherita Rimini ◽  
Pierfrancesco Franco ◽  
Berardino De Bari ◽  
Maria Giulia Zampino ◽  
Stefano Vagge ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Anal Cancer ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
External Validation ◽  
Risk Groups ◽  
Anal Squamous Cell Carcinoma ◽  
Predictors Of Response ◽  
Risk Patients

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Index ◽  
Predictive Marker ◽  
Risk Groups ◽  
Two Factors ◽  
One Year ◽  
Metastatic Sites ◽  
Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

scholarly journals MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Morten Lindhardt ◽  
Nete Tofte ◽  
Gemma Currie ◽  
Marie Frimodt-Moeller ◽  
Heiko Von der Leyen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
High Risk ◽  
Risk Group ◽  
Cox Model ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Renal Function Decline

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &gt; 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &lt; 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&lt;0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&lt;0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

scholarly journals Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Risk Group ◽  
Risk Groups ◽  
Rank Test ◽  
Intermediate Risk ◽  
Free Survival ◽  
Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

Pre-Transplant Variables Affecting the Outcome of Submyeloablative Allogeneic HSCT in Uniformly Treated Patients with Hematologic Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2324-2324
Author(s):  
Jayesh Mehta ◽  
S. Singhal ◽  
M. Tallman ◽  
S. Williams ◽  
J. Winter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Risk Factor ◽  
High Risk ◽  
Cox Model ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Allogeneic Hsct ◽  
High Risk Factors

Abstract The outcome of 63 consecutive submyeloablative allografts (27–66 y, median 52) performed for hematologic malignancies after 100 mg/m2 melphalan without (n=21; prior autograft) or with (n=42; no prior autograft) 50 mg/kg cyclophosphamide was analyzed to study the effect of pre-transplant characteristics. GVHD prophylaxis comprised cyclosporine-mycophenolate (n=37; HLA-identical sibling donors) or tacrolimus-mycophenolate (n=26, 1-locus mismatched sibling or 9–10/10 allele-matched unrelated). No growth factors were administered routinely post-transplant and supportive care was uniform. 14 patients experienced transplant-related mortality (TRM), and 32 relapsed. 24 relapsing patients died, and 7 of the other 8 are alive in CR or with declining disease. The following factors were analyzed in a Cox model for their effect on TRM and relapse: chemosensitive (n=25) vs refractory disease (n=38), age ≤55 (n=44) vs >55 (n=19), normal (n=32) vs abnormal (n=31) LDH, HLA match (n=56) vs mismatch (n=7), prior autograft or not, performance status 0–1 (n=47) vs 2–3 (n=16). Outcome Favorable factor RR (95% CI) P TRM Age ≤55 0.20 (0.04–0.86) 0.03 HLA matched 0.21 (0.05–0.89) 0.04 Performance status 0-1 0.25 (0.06–0.99) 0.05 Relape Chemosensitive disease 0.28 (0.11–0.73) 0.01 Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Table 2 shows the causes of death by risk factors for TRM and disease chemosensitivity. Group (n) Alive TRM Death from disease A: 2 risk factors for TRM (7) 1 (14%) 5 (71%) 1 (14%) B: 1 risk factor for TRM + Refractory (19) 2 (11%) 6 (32%) 11 (58%) C: 1 risk factor for TRM + Sensitive (9) 5 (56%) 1 (11%) 3 (33%) D: 0 risk factor for TRM + Refractory (12) 3 (25%) 1 (8%) 8 (67%) E: 0 risk factor for TRM + Sensitive (16) 13 (81%) 1 (6%) 2 (13%) These data suggest that while the current treatment approach is optimal for patients falling in Group E, modified approaches are needed for other patients. Based on the causes of failure, the following modifications appear to be warranted. Group A: A completely non-ablative regimen to reduce toxicity. Group B: A completely non-ablative regimen to reduce toxicity with augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group C: Augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group D: Conventional-intensity rather than reduced-intensity allogeneic HSCT.

Comorbidities and FLT3 Abnormalities as Independent Prognostic Indicators of Survival in Elderly Acute Myeloid Leukemia Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3983-3983
Author(s):  
Massimo Breccia ◽  
Roberto Latagliata ◽  
Laura Cannella ◽  
Ida Carmosino ◽  
Caterina Stefanizzi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Renal Impairment ◽  
Prognostic Score ◽  
Performance Status ◽  
Prognostic Impact ◽  
Prognostic Parameters ◽  
Biological Features ◽  
Cell Counts ◽  
Comorbidity Index

Abstract Elderly AML patients have a dismal prognosis due to biological features of disease in itself and to presence of comorbidities. Aim of present study was to evaluate the prognostic impact of comorbidity prognostic score systems applied in our population of patients, as well as of other clinical-biological features. We retrospectively considered the outcome of 120 patients aged &gt; 65 years diagnosed as having AML between January 2001 and December 2005. Comorbidities were investigated retrospectively and 3 scores were applied to the whole patient population: the modified Charlson comorbidity index (CCI), the Hematopoietic cell transplantation-comorbidity index (HCTCI) and the score proposed by Dombret et al at ASH 2006, which considered as prognostic parameters documented infections at presentation, presence of chronic pulmonary diseases, PS &gt;1 and high risk cytogenetic category. For all patients clinical and biological features at presentation (age, sex, WHO performance status, prior hematological disorder, presence of fever and/or documented infection, percentage of BM and PB blast cells, blood cell counts, hemoglobin level, coagulation tests) were analysed as well as survival with respect to the presence or not of FLT3 abnormalities. Median age of whole population was 62 years. Sixty-eight patients (57%) were aged &gt;70 years. Thirty-five patients (29%) had an antecedent myelodysplastic phase. Cytogenetic analysis showed high frequency of intermediate/high risk karyotype and immunophenotype showed 62 patients (52%) to be positive for CD34 expression. Renal impairment was evident at diagnosis in 11 patients. Molecular analysis showed FLT3 as unique abnormality in 11 patients (9%). Comorbidity conditions at diagnosis included cardiac dysfunction in 46 patients, diabetes in 10 patients, other neoplasias in 3 patients, pulmonary disease in 18 patients, renal impairment in 7 patients and infections documented at diagnosis in 16 patients. Score was low (0–1) in 70% of patients by CCI, in 40% by HCT-CI and in 80% by Dombret et al criteria. In univariate analysis we tested presenting features which were associated with worse outcome. We found a significant association between a shorter survival and leukocytosis &gt; 100 × 109/l (p=0.005), antecedent myelodysplastic phase (p=0.04), high-risk karyotype (p=0.05), FLT3 abnormalities (p=0.03), fever at presentation (p=0.023), CCI stratification (p=0.027) and Dombret et al stratification (p=0.045). Age, sex, performance status, and presence of CD34 antigen positivity were not independent prognostic parameters. In the multivariate analysis leukocytosis (p=0.0013), antecedent MDS (p=0.011), FLT3 abnormalities (p=0.032), CCI (p=0.0037) and Dombret et al score (p=0.045) were confirmed as independent prognostic parameters for survival. Based on results of multivariate analysis for survival we stratified elderly patients into two risk groups according to the presence or not of the following risk factors: leukocytosis, antecedent MDS phase, FLT3 abnormalities, CCI or Dombret et al score &gt; 2. Patients were considered as low risk if they had none or only one of the above mentioned adverse factors for survival: these patients had a median OS of 447 days. Patients with two or more adverse factors were categorized as high risk: this subgroup had a median OS of 227 days (p=0.001). In conclusion, comorbidities are independent factors that influence survival. Application of CCI and Dombret score may help to better identify patients at diagnosis who can benefit from intensive chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document