Summary
The International Prognostic Index (IPI) is the most widely used score for non‐Hodgkin lymphoma but lacks the ability to identify a high‐risk population in diffuse large B‐cell lymphoma ...(DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red‐cell distribution width (RDW) has been associated with inflammation and beta‐2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R‐CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG‐PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression‐free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3–4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high‐risk subgroup with five‐year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)‐IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real‐life practice without additional tests. Compared to R‐IPI, it shows a more precise high‐risk assessment and risk discrimination for both PFS and OS.
Summary
The study included 1848 diffuse large B‐cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International ...Prognostic Index (NCCN‐IPI) and explore the effect of adding high Beta‐2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN‐IPI variables in order to develop an improved index. Comparing survival curves, NCCN‐IPI discriminated better than IPI, separating four risk groups with 5‐year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high‐risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III‐IV, and β2M as independently significant, whereas the NCCN‐IPI‐selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)‐IPI developed here, with 7 points, significantly separated four risk groups (0, 1–3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5‐year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN‐IPI. In conclusion, GELTAMO‐IPI is more accurate than the NCCN‐IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high‐risk group and is not influenced by primary extranodal presentation or treatments of different intensity.
The study included 1848 diffuse large B-cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International Prognostic ...Index (NCCN-IPI) and explore the effect of adding high Beta-2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN-IPI variables in order to develop an improved index. Comparing survival curves, NCCN-IPI discriminated better than IPI, separating four risk groups with 5-year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high-risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III-IV, and β2M as independently significant, whereas the NCCN-IPI-selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)-IPI developed here, with 7 points, significantly separated four risk groups (0, 1-3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5-year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN-IPI. In conclusion, GELTAMO-IPI is more accurate than the NCCN-IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high-risk group and is not influenced by primary extranodal presentation or treatments of different intensity.
Summary
The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO‐IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated ...with immunochaemotherapy: low (LR), low‐intermediate (LIR), high‐intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO‐IPI in the DLBCL subtypes defined by the immunohistochaemistry‐based Hans algorithm, Germinal Centre B (GCB) and non‐GCB. A multivariate Cox regression model including GELTAMO‐IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non‐GCB) and both the GELTAMO‐IPI and the COO subtype in 780 (353 GCB; 427 non‐GCB). There were no differences in 5‐year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO‐IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO‐IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5‐year OS of 100%, 75% and 52%, respectively. In the non‐GCB subtype, LR, the combined LIR+HIR and HR had a 5‐year OS of, 97%, 82% and 35% respectively. GELTAMO‐IPI identifies a genuine poor outcome group of patients in the DLBCL non‐GCB subtype.
El conocimiento de las especies de insectos existentes en zonas protegidas es de enorme interés para cuantificar su biodiversidad. En este trabajo se presentan las once especies de la tribu Lamiini ...(Coleoptera: Cerambycidae) registradas en la Reserva Biológica Alberto Manuel Brenes (San Ramón, Costa Rica): Plagiohammus albatus, Plagiohammus elatus, Plagiohammus emanon, Plagiohammus rubefactus, Plagiohammus spinipennis, Deliathis nivea, Deliathis quadritaeniator, Neoptychodes cretatus, Ptychodes politus lecontei, Taeniotes praeclarus, Taeniotes scalatus y Taeniotes xanthostictus. Dos de ellas (P. albatus y P. elatus) son nuevas citas para la zona estudiada. De todas las especies identificadas se aportan figuras, datos descriptivos, registros de capturas y nivel de abundancia.
The knowledge of present species in protected areas has a great interest in order to estimate their biodiversity. In this work, we collected samples of the tribe Lamiini (Coleoptera: Cerambycidae) in the Reserva Biológica Alberto Manuel Brenes, San Ramón, Costa Rica. Eleven species of Lamiini were identif ied: Plagiohammus albatus, Plagiohammus elatus, Plagiohammus emanon, Plagiohammus rubefactus, Plagiohammus spinipennis, Deliathis nivea, Deliathis quadritaeniator, Neoptychodes cretatus, Ptychodes politus lecontei, Taeniotes praeclarus, Taeniotes scalatus and Taeniotes xanthostictus. Two of these (P. albatus and P. elatus) are new for the studied area. Figures, descriptions, collection dates and their abundance level are provided from each identified species.
Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. ...Convinced that one of the best tools to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary.
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Backgound. GELTAMO-IPI has shown to have better prognostic effect than NCCN-IPI for DLBCL treated with immunochemotherapy (BJH;2017;176;918) with the additional advantages to identify a real high ...risk group and not being influenced by the primary extranodal presentation or the use of treatment more intense than R-CHOP. The variables in GELTAMO-IPI and its statistical weight are: age (<65 years: 0 points; ≥65-79:1 pt.; ≥80 2 pt.), PS (0-1: 0 p.; 2: 1pt. ≥2: 2 pt.), >LDH, > β2mcg and stage IV, one point each. The combination of these factors separate four risk groups, Low risk (LR, 0 points), Low-Intermediate risk (LIR, 1-3 points), High-Intermediate risk (HIR, 4 points and High Risk (HR≥5 points), with 5-year overall (5y-OS) survival of 93%, 79%, 66% and 39%, respectively.
Aims. Present study explores the prognostic effect of GELTAMO-IPI in the histological subgroups depending of the cell of origin: B Germinal Center (BGC) or non B Germinal Center (Non-BGC).
Methods. the original series for the development of GELTAMO-IPI comprised 1848 patients. The BGC/non-BGC origin was calculated with the Hans algorithm by the Immunohistochemical expression of 3 markers (CD10, BCL6 and MUM-1) being available in 1097 patients. The statistical study consisted in the development of a Cox model which includes the three variables: GELTAMO-IPI groups (LR, LIR, HIR, HR), cell of origin (BGC/non-BGC) and its product in order to evaluate the presence of interaction between these variables. Kaplan-Meier and Log-rank were used for survival curves and comparison.
Results. The cell of origin was retrieved in 1097 patients: 380 BGC, 459 non-BGC and 258 non-evaluable. The series includes: LR 72 p. (9.2%), LIR 464 p. (59.5%), HIR 127 p. (16.3%) and HR 117 p. (15%) with 5y-OS of 98%, 79%, 67% and 41%, respectively. The Cox model showed interaction between the risk groups and the GBC/non-GBC origin (p=0.005), indicating that GELTAMO-IPI has a different effect in each group. In the BGC-DLBCL group with LR (34 p.), LIR (221 p.), HIR (53 p.) and HR (45 p.) the 5y-OS differences between LR and LIR are maintained (100%, 75%, respectively), but not between HIR and HR (53% and 51%); Nevertheless, GELTAMO-IPI stratified 3 distinct risk groups (LR, LIR and HIR+HR), although it is not able to identify a real high risk group of patients (Figure 1, left panel). In the Non-BGC-DLBCL the differences among the LR, LIR and HIR groups (38, 243, and 74 patients with 5y-OS of 97%, 82% and 77%) have lower significance than in the original study (p=0.01 and p=0,26, respectively), but a distinct HR group of 72 patients with a 5yOS of 35% is clearly identified (p<0.001) (Figure 1, right panel).
Conclusions. GELTAMO-IPI separates three risk groups in BGC-DLBCL, but fails to identify a genuine HR group, whereas GELTAMO-IPI in the non-BGC-DLBCL positively identifies a real high risk group. This different outcome in the GC-DLBCL and non-GC-DLBCL using simple clinical factors, as included in GELTAMO-IPI, represents an interesting practical prognostic tool in the clinical practice.
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Diaz-Lopez:TFS: Employment. Martín:Gilead: Consultancy; Janssen: Honoraria; Servier: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Sancho:Roche: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Laboratorios Servier: Consultancy; Kern Pharma: Honoraria; Mundipharma: Honoraria. Salar:Servier: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau. Gutierrez:JANSSEN: Consultancy, Research Funding, Speakers Bureau; ROCHE: Research Funding, Speakers Bureau; SERVIER: Speakers Bureau; GILEAD: Honoraria; TAKEDA: Speakers Bureau; PFIZER: Consultancy. Lopez-Guillermo:Janssen: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Roche: Consultancy, Other: Research grant; Novartis: Consultancy.
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Introduction
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive B cell lymphomas, considering their biologic, pathological and clinical backgrounds. However, treatment of ...DLBCL is relatively homogeneous and standard, mainly based in the R-CHOP regimen. Several prognostic scores have been proposed for categorizing the risk and finding those with worse results with standard treatment, suitable to be treated with new schemes or drugs. The most important and widely used is the International Prognostic Index (IPI) proposed in 1993 and lately validated in the rituximab era (R-IPI). However, being a good prognostic score lacks the ability to identify a very high risk prognostic subset in the rituximab era. Trying to improve this situation several attempts have been made including NCCN-IPI or GELTAMO-IPI. In 1992, the MD Anderson Cancer Centre (MDACC) reported a prognostic score considering exclusively variables related to the tumor: the Tumor Score (TS). Two of them already present in IPI: high LDH and Ann Arbor stage III-IV but three different: high beta-2-microglobulin (B2M), bulky mass and presence of B symptoms. This index has not been studied in the rituximab era. Our aim is to validate the TS in the rituximab era and analyze its current potential role.
METHODS
From the nation-wide database of DLBCL of the Grupo Español de Linfoma y Trasplante de Médula Ósea (GELTAMO), we included for the validation those patients homogenously treated with R-CHOP and with all five TS variables available (n=1294). Patients had to be ≥ 18 years-old and a minimum of 1 year of follow-up; all histological subtypes of DLBCL and primary extranodal cases were acceptable, with the only exclusion of primary testicular or CNS sites. Failure-free survival (FFS) (including disease progression, no response to treatment or death events) and overall survival (OS) were analyzed with the Kaplan-Meier method and compared with the log-rank test. Cox Regression models were used for univariate and multivariate analysis. Comparisons between scores were performed with concordance probability estimates (CPEs).
RESULTS
Median follow-up was 60 months (12-176). 5y-FFS and OS of the series were 62% and 74%, respectively. All the variables of the original TS retained an independent prognostic role in our series. The TS in the rituximab era (R-TS) remains predictive and clearly identifies four different risk groups (Figure 1A), finding a particularly high risk subset with a worse outcome (5y-FFS of 29%). Comparison between TS and the other indexes (IPI, NCCN-IPI or GELTAMO-IPI) showed similar CPEs for FFS in our series: 0.64 vs 0.64, 0.64 and 0.65, respectively (Figure 1B). However, TS has a better discrimination of the higher risk subgroup than IPI (5y-FFS of 47%) and NCCN-IPI (5y-FFS of 39%), and the same that GELTAMO-IPI but with a better consistency between points of the score. As R-IPI and R-TS have complementary information, another option was combining R-IPI and R-TS: patients within high risk by R-IPI (5y-FFS of 47%) when tested with R-TS can be further subdivided in three risk categories (intermediate low, intermediate high and high with 5y-FFS of 75%, 61% and 37%, respectively). To further improve the ability of finding a very high risk subset with the variables included in TS, we tested categorizing B2M normalized (normal, >1 and >3), LDH normalized (normal, >1 and >3) and AA stage (I, II and III-IV). With these changes the new enhanced TS could identify a higher risk group with a 5y-FFS of 20% and a median FFS of 7 months (Figure 1C and 1D).
CONCLUSIONS
1) All variables included in the original MD. Anderson TS retain an independent prognostic role in the rituximab era, including B symptoms, B2M and bulky mass; 2) TS remains predictive of FFS and OS in the rituximab era with a similar CPE in discrimination when compared to previously reported prognostic scores; 3) TS and GELTAMO-IPI showed a better identification of patients with high risk prognosis compared to IPI or NCCN-IPI; 4) R-IPI and R-TS may be combined in order to easily improve risk classification of DLBCL patients; 5) Further categorization of LDH, B2M and AA stage increased the ability of TS to identify high risk subsets of DLBCL; 6) TS could be a backbone for introducing other new molecular or biologic tumor related prognostic factors.
Figure 1. FFS using R-TS (1A), R-IPI (1B) and enhanced TS (1C). OS using enhanced TS (1D).
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Gutierrez:SERVIER: Speakers Bureau; GILEAD: Honoraria; TAKEDA: Speakers Bureau; PFIZER: Consultancy; JANSSEN: Consultancy, Research Funding, Speakers Bureau; ROCHE: Research Funding, Speakers Bureau. Diaz-Lopez:TFS: Employment. Lopez-Guillermo:Roche: Consultancy, Other: Research grant; Celgene: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Novartis: Consultancy. Martín:Roche: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Janssen: Honoraria; Gilead: Consultancy. Salar:Roche: Speakers Bureau; Janssen: Speakers Bureau; Servier: Speakers Bureau.
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