The Absolute Monocyte and Lymphocyte Counts at Diagnosis Predict Survival and Identify High-Risk Patients In Diffuse Large-B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3088-3088
Author(s):  
Ryan A. Wilcox ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
David James Inwards ◽  
Ivana Micallef ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Confidence Interval ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Good Risk

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1136-1143 ◽  
Author(s):  
Sharon L. Barrans ◽  
Ian Carter ◽  
Roger G. Owen ◽  
Faith E. Davies ◽  
Russell D. Patmore ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P &lt; .0001) and bcl-2 (R = 0.14, P = .0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = −0.025, P = .02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2− group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.

IPI In Selecting Patients With Diffuse Large B Cell Lymphoma in Rituximab Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5063-5063
Author(s):  
Sonja Genadieva-Stavrik ◽  
Alexandra Pivkova ◽  
Zlate Stojanoski ◽  
Borce Georgievski
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Abstract Nowadays, goal of treatment approach in diffuse large B cell lymphoma is cure and first step towards it is to achieve complete remission. DLBCL is a potentially curable disease, with curability highly dependent on clinical and biological features. According to the WHO classification of Hematological Malignancies, the entity of DLBCL is characterized by rapidly growing mature B cell tumors with large or relatively large cells and /includes a number of disease variants/entities / encompassing several distinct clinopathologic diseases, several different histologic variants and clinical subtypes. There is no unique treatment for all patients with diffuse large B cell lymphoma. Different subgroup of patients with DLBCL needs different treatment. In the pre-rutuximab era International Prognostic Index (IPI) was considered to be the most important prognostic factor for survival and the strongest indicator for identification of high-risk patients, who are unlikely to be cured with standard chemotherapy. Having in mind that IPI is based on 5 clinical characteristics (age, performance status, stage, extranodal involvement, LDH level) and it is constructed in the pre-rituximab is clear that R-IPI should be tested in rituximab era to provide any information of its validity. We retrospectively analyzed unselected population of 80 patients with confirmed diagnose of diffuse large B cell lymphoma treated at University hematology department in the period of 2005-2010. All patients were uniformly treated with R-CHOP regiment as initial treatment with curative intent. There were 80 patients with mean age 54, 5 years (15-84), male 35 and female 45. Older than 60 years were 29 patients (36, 25%). More than half of the patients (42) were diagnosed in advanced stage of the disease. We analyzed five prognostic factors: age, performance status, stage, extranodal involvement, LDH level and through the multifactorial analyses we selected two groups of patients. One with 0 to 2 factors as patients with low risk. Patients with more than 3 factors are considered as high risk. There is statistically significant difference in overall survival between two groups with five –years overall survival 70% for low risk patients and 47% for high risk. High-risk patients may be candidates for autologous transplantation as initial treatment, having in mind that in the rituximab era relapses occur very early in the first year and are difficult to be treated. R-IPI score is significant predictor and should be used for risk stratification of patients with aggressive B-cell lymphoma. However, these findings should be validated prospectively in an independent population of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Deep Phenotypic Analysis Reveals a Monocyte Subpopulation Predictive of Relapse/Refractory Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2863-2863
Author(s):  
Edward Truelove ◽  
Frances Seymour ◽  
Janet Matthews ◽  
John G. Gribben
Keyword(s):  
Peripheral Blood ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Peripheral Blood Monocyte ◽  
Blood Monocyte ◽  
Phenotypic Analysis ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Good Risk

Abstract Background: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma subtype with up to two thirds of patients achieving cure following standard immuno-chemotherapy. However, approximately 10-15% will be primary refractory and a further 20-30% relapse. There is an urgent need for improved biomarkers to identify these poor risk patients at diagnosis who are destined to fail standard therapy so that novel approaches can be considered. The diagnostic peripheral blood monocyte count is known to be predictive of outcome in DLBCL, with higher counts identifying patients with worse outcome but mechanistic understanding is currently lacking. The aim of this study was to investigate the peripheral blood monocyte population driving this phenomenon and we present here a deep phenotypic analysis of the monocyte compartment at diagnosis in patients with extremes of outcome following immuno-chemotherapy. Methods: We identified 112 immuno-chemotherapy treated DLBCL patients with viably cryopreserved peripheral blood mononuclear cells (PBMCs) in our tissue bank. The diagnostic absolute monocyte (AMC) and lymphocyte counts (ALC) were examined as prognostic variables. For phenotypic analysis a subset of 20 patients, 10 with relapse/refractory disease within 12 months of therapy (Poor risk) and 10 with continued complete remission >24 months post therapy (Good risk), were selected. PBMCs from these patients were stained with a panel of 29 metal-tagged antibodies designed to identify immune populations and characterize the monocyte compartment and analyzed using cytometry by time-of-flight (CyTOF2TM). Samples were acquired in batches run with the same healthy donor control PBMCs to ensure consistency of staining. Normalized data were subjected to traditional Boolean gating in Cytobank (www.mrc.cytobank.org) to identify CD45+ live single cells and further analyzed using FlowSOM and CITRUS. Results: In the full 112 patient cohort, a higher diagnostic AMC (≥0.6 x 109/L) predicted worse outcome (5-year OS, 59% vs 74%, p=0.047*). The lymphocyte to monocyte ratio (LMR) was more discriminatory, with a low LMR (<2.6) predicting worse outcome (5-year OS, 49% vs 81%, p=0.0009*). CyTOF analysis of the CD45+ events from all 20 DLBCL patients were clustered in an unsupervised manner with FlowSOM and visualized according to the tSNE algorithm. This identified all expected immune populations with further subdivision into multiple clusters / sub-populations based on protein marker expression. Repeating the FlowSOM analysis by outcome revealed clusters with clear differences between the 2 groups, including striking changes to the monocyte compartment (Figure 1). CITRUS, an algorithm for automated biomarker discovery, was used to further assess the differences in the monocyte compartments between poor risk and good risk DLBCL patients. This identified a monocyte subset, representing approximately 10% of non-lymphoid CD45+ PBMCs, with increased abundance in poor risk patients with relapsed/refractory disease (p=0.0028*, Figure 2). This subset expressed markers including HLA-DR, CD11b, CD13, CD14, CD33, SIRPα (CD172a), CCR2 (CD192, monocyte chemo-attractant protein receptor), CD206 and PD-L1 (CD274). Conclusions: We confirmed the previous finding that the diagnostic AMC is predictive of outcome in our cohort of DLBCL patients and have identified differences in the peripheral blood monocyte compartment between patients with good and poor risk disease. Unsupervised analysis using FlowSOM identified monocyte clusters with greater abundance in poor risk patients. A second high-dimensional single cell data analysis algorithm, CITRUS validated this finding by revealing a stratifying monocyte sub-population that was enriched in poor risk patients. This phenotype of peripheral blood monocytes may account for the adverse nature of a higher AMC at diagnosis. We are now functionally characterizing these monocytes and evaluating their relationship to differences between the lymphoid populations of good and poor risk patients. Disclosures Seymour: Celgene: Research Funding. Gribben:Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria; Abbvie: Honoraria; Kite: Honoraria; Acerta Pharma: Honoraria, Research Funding; Wellcome Trust: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; NIH: Research Funding; Unum: Equity Ownership; Roche: Honoraria; Novartis: Honoraria; Cancer Research UK: Research Funding; Medical Research Council: Research Funding; TG Therapeutics: Honoraria.

Serum Albumin and Peripheral Blood Lymphocyte/Monocyte Ratio at Diagnosis May Provide Additional Prognostic Information in R-IPI Good Risk Diffuse Large-B-Cell Lymphoma Patients Treated with R-CHOP

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2658-2658 ◽  
Author(s):  
Branimir Spassov ◽  
Donka Vassileva ◽  
Georgi Michaylov ◽  
Gueorgui Balatzenko ◽  
Margarita Guenova
Keyword(s):  
Risk Group ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Prognostic Information ◽  
Poor Risk ◽  
Risk Patients ◽  
Good Risk

Abstract Background and Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Currently, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP) and the prognostic stratification is performed by the Revised International Prognostic Index (R-IPI), identifying 3 distinct prognostic groups with a very good, good and poor outcome. A lot of new prognostic markers have been introduced into the clinical practice to perform better pts' stratification. Particular prognostic relevance has been attributed to serum albumin (SA), β2-microglobulin (B2M), peripheral blood lymphocyte/ monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR) etc. However the data of these prognostic factors across the different R-IPI prognostic groups are limited. Therefore, we decided to access whether SA, B2M, LMR and NLR were predictors of overallsurvival (OS) across the different R-IPI groups of R-CHOP treated DLBCL pts. Patients and Methods: We retrospectively reviewed the clinical outcome of 281 R-CHOP treated DLBCL pts with median age 58 years and 51.8 % male. According to the R-IPI score, the pts in very good, good and poor risk were 24.2%, 54.8% and 21%, respectively. Laboratory levels of albumin, absolute lymphocyte, monocyte and neutrophil count were recorded, and LMR and NLR - calculated. Serum B2M levels were measured by radioimmunoassay. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models. Results: The estimated 5-year OS was 87.1%, 74% and 31% for R-IPI very good, good and poor-risk patients, respectively. The median values of SA, B2M, LMR and NLR were 40.7 g/L, 2.9 mg/L, 2.95 and 2.86, respectively. Our data showed that on univariate analysis inferior OS was associated with decreased SA (≤39.4 g/L; 95% confidence interval (CI) 0.70-0.82, p=<0.001), elevated B2M (>2.6 mg/L; 95% CI 0.68-0.80, p=<0.001), reduced LMR (≤2.16; 95% CI 0.71-0.81, p=<0.001) and increased NLR (>2.61; 95% CI 0.66-0.77, p=<0.001), presented as dichotomized variables. On multivariate analysis the independent prognostic significance was confirmed only for SA and LMR, with hazard ratios of 0.23 (95% CI 0.11-0.49, p<0.001) and 0.41 (95% CI 0.21-0.81, p=0.011), respectively. Based on the dichotomized SA and LMR values a SA/LMR prognostic index (PI) was created stratifying patients into 3 risk groups: very good (SA >39.4 g/L and LMR >2.16; n=75), good (SA ≤39.4 g/L or LMR ≤2.16; n=52) and poor-risk (SA ≤39.4 g/L and LMR ≤2.16; n=41) populations. The estimated 5-year OS was 88.7% for very good, 51.7% for good, and 8.8% for poor SA/LMR PI group (p<0.001). Median OS for poor-risk patients was 1.1 years (95% CI 1.03-1.72 years) and not reached for both the very good and good-risk groups. We sought to determine whether the SA/LMR PI may provide additional prognostic information within the R-IPI risk groups. Due to low number of deaths - 4.4% (3/68), no statistics could be calculated in very good R-IPI risk group. Within the R-IPI good risk patients SA/LMR PI allowed us to discriminate 3 subgroups, characterized by significant differences in 3-year and median OS (Figure 1): a SA/LMR PI poor risk subgroup (n=18) with 10.4% 3-years OS and 1.13 years (95% CI 0.82-1.44 years) median OS; a SA/LMR PI good risk subgroup (n=32) with 59.5% 3-years OS and median not reached; and a SA/LMR PI very good risk subgroup (n=50) with not reached median OS and 91.3% 3-years OS comparable to the OS in R-IPI very good patients (p=0.229). Only SA retained its independent prognostic significance in R-IPI poor risk group. Conclusion: SA and LMR are independent prognostic markers to predict survival in DLBCL pts. Adding these variables to prognostic models such as the R-IPI score might improve their predictive ability, providing particularly relevant information within the R-IPI good risk group. A subgroup of R-IPI good risk pts with a very good SA/LMR PI was identified, comparable to the R-IPI very good risk category in terms of OS. Figure 1. Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis Figure 1. Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis Disclosures No relevant conflicts of interest to declare.

scholarly journals Open-Labeled, Multicenter Phase II Study of Bortezomib for Maintenance Therapy in Patients with High Risk Diffuse Large B Cell Lymphoma (DLBCL): Borma Trial from Consortium for Improving Survival of Lymphoma (CISL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2884-2884
Author(s):  
Jae-Cheol Jo ◽  
Ho Sup Lee ◽  
Cheolwon Suh ◽  
Hye Jin Kang ◽  
Won Seog Kim ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
B Cell ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Risk Patients ◽  
Large B Cell Lymphoma ◽  
Risk Patients

Background: High-intermediate or high risk in international prognostic index (IPI) has a long-term chance of cure in the range about 50% in patients with diffuse large B cell lymphoma (DLBCL) treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib inhibits NF-κB activation through proteasome inhibition, providing rationale for its use in cells that constitutively express NF-κB. Non-germinal center B cell (GCB) DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic NF-κB pathway, which can inhibit chemotherapy. There is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed complete response (CR) after treated with R-CHOP. Methods: Patients with newly diagnosed stage II(bulky)-IV DLBCL with high or high intermediate IPI score of 3 to 5, and patients achieving a CR at the end of 6 or 8 cycles of R-CHOP21 were eligible for enrollment. Non-GCB DLBCL according to Hans criteria confirmed by central review was need before enrollment. Bortezomib maintenance treatment was consisted of bortezomib 1.3mg/m2 subcutaneously administration day 1 and day 15 per 28-day cycle with a total of 12 cycles. The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints were 3-year overall survival (OS), and toxicites. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: Fifty-nine patients were enrolled between May 2014 and Oct 2018. The type of Non-GCB DLBCL in all patients was confirmed by the central pathology review. The median age was 65 years (range: 27-86 years), and 60% were > 61 years. The baseline clinical features were as follows: female sex, 45.8%; ECOG >1, 10.2%; stage II bulky (>10cm), 6.8%; stage III/IV, 93.2%. At the time of analysis, 29 patients completed 12-cycles of bortezomib maintenance, and 3 patients is ongoing. Seven patients did not finished maintenance therapy due to toxicities (fatigue, atrial flutter, neuropathy, pleural effusion, thrombocytopenia), and withdrawal of informed consent (n=4). Sixteen patients experienced disease progression during bortezomib maintenance treatment. With a median follow-up of 25.1 months, 3-year PFS rate was 56.9% and 3-year OS rate was 86.4% (Figure 1). Toxicity was assessed in 489 cycles of bortezomib maintenance in all 59 patients. There was no treatment-related death and febrile neutropenia. Conclusion: Bortezomib maintenance showed 3-year PFS rate of 56.9% with acceptable toxicities in patients with high risk DLBCL achieving a CR at the end of 6 or 8 cycles of R-CHOP21. Figure 1 Disclosures Kim: Celltrion: Research Funding; Novartis: Research Funding; J + J: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Charlson Comorbidity Index Is An Independent Prognostic Factor Among Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3923-3923
Author(s):  
Jin Takeuchi ◽  
Atsuko Hojo
Keyword(s):  
Elderly Patients ◽  
Charlson Comorbidity Index ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Poor Risk ◽  
Risk Patients ◽  
Comorbidity Index ◽  
Good Risk

Abstract 3923 Poster Board III-859 Introduction Wide use of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has improved the clinical outcome for elderly patients with DLBCL; however, a higher prevalence of coexisting disorders remains a problem. Correlation between their comorbidities and prognosis has not yet been well investigated. Patients and methods We retrospectively analyzed all patients over 65 years old who had been newly diagnosed with DLBCL at our institution from 2001 to 2008. To assess their comorbid medical status, we calculated the Charlson Comorbidity Index (CCI) for patient excluding primary disease. Prognostic factors were identified by Cox proportional hazards regression model. We classified patients into a low CCI group (CCI 0-1) and a high CCI group (CCI 2 or higher). Kaplan-Meyer curves for each group were evaluated by logrank test. Results A total of 80 patients were enrolled in this analysis. The median age was 73 (range 66-90) and the median observation period was 28 months (range 4-90 months). 62 patients (77.5%) were treated with R-CHOP, 15 (18.6%) underwent some other regimen, and 3 (3.8%) were given best supportive care only. According to revised International Prognostic Index (r-IPI), 43 patients were in the good risk group and the others were in the poor risk group. The estimated 3 year over all survival (OS) rate for these groups were 90% and 45% (p<0.0001). As for CCI, 14 patients (17.5%) were assigned to the high CCI group. Multivariate analysis revealed high CCI was associated with worse OS, while independent of r-IPI [Hazard Ratio (HR) 3.20, 95% Confidence interval (CI) 1.28-7.41, p=0.0145]. Among r-IPI poor risk patients, the high CCI group was inferior to the low CCI group for the 3 year OS rate (14% vs 56% p=0.0358), whereas this was not significant among r-IPI good risk patients (69% vs 94% p=0.0617). Conclusions Among elderly patients with DLBCL, high CCI is independently associated with poor survival. Patients having both poor r-IPI and high CCI may need discrete strategies. Disclosures: No relevant conflicts of interest to declare.

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 1989-1996 ◽  
Author(s):  
Paul A. Hamlin ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Jing Qin ◽  
Jaya M. Satagopan ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Second Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P &lt; .001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P &lt; .001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.

Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

2007 ◽  
Vol 25 (17) ◽  
pp. 2426-2433 ◽  
Author(s):  
Silvia Montoto ◽  
Andrew John Davies ◽  
Janet Matthews ◽  
Maria Calaminici ◽  
Andrew J. Norton ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). Patients and Methods From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. Results The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. Conclusion Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.

Sign in / Sign up

Export Citation Format

Share Document