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Objective The purpose of this study was to evaluate the prognostic significance of corrected baseline metabolic parameters in fluorodeoxyglucose positron emission tomography imaging ( 18 F-FDG PET/CT) for 3-year progression-free survival (PFS) in patients with primary diffuse large B cell lymphoma (DLBCL). Patients and Methods Retrospective clinical and pathological data were collected for 199 patients of DLBCL diagnosed between January 2018 and January 2021. All patients underwent 18 F-FDG PET/CT scans without any form of treatment. The corrected maximum standardized uptake value (corSUVmax), corrected mean standardized uptake value (corSUVmean), corrected whole-body tumor metabolic volume sum (corMTVsum), and corrected total lesion glycolysis of whole body (corTLGtotal) were corrected using the SUVmean in a 1-cm diameter mediastinal blood pool (MBP) from the descending thoracic aorta of patients. Kaplan-Meier survival curves and Cox regression were used to examine the predictive significance of corrected baseline metabolic parameters on 3-year PFS of patients. The incremental values of corrected baseline metabolic parameters were evaluated by using Harrell's C-indices, receiver operating characteristic, and Decision Curve Analysis. Results The multivariate analysis revealed that only the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and corMTVsum had an effect on 3-year PFS of patients ( p < 0.05, respectively). The Kaplan-Meier survival analysis demonstrated significant differences in PFS between the risk groups classified by corSUVsum, corMTVsum, and corTLGtotal (log-rank test, p < 0.05). The predictive model composed of corMTVsum and corTLGtotal surpasses the predictive performance of the model incorporating MTVsum and TLGtotal. The optimal performance was observed when corMTVsum was combined with NCCN-IPI, resulting in a Harrell's C index of 0.785 and area under the curve values of 0.863, 0.891, and 0.947 for the 1-, 2-, and 3-year PFS rates, respectively. Conclusion The corMTVsum offers significant prognostic value for patients with DLBCL. Furthermore, the combination of corMTVsum with the NCCN-IPI can provide an accurate prediction of the prognosis.

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BACKGROUND: MYC/BCL2 double expression (DE) is associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). This study aimed to determine whether the addition of DE to the National Comprehensive Cancer Network Internal Prognostic Index (NCCN-IPI) could improve the prediction of disease progression in patients with DLBCL treated with R-CHOP. METHODS: This confirmatory prognostic factor study retrospectively recruited patients with newly diagnosed DLBCL between January 1, 2014, and January 31, 2018, at Ramathibodi Hospital (RA) and Thammasat University Hospital (TU). The follow-up period ended on July 1, 2022. Tumors expressing MYC ≥ 40% and BCL2 ≥ 50% were classified as DE. We calculated the hazard ratios (HR) for progression-free survival (PFS) from the date of diagnosis to refractory disease, relapse, or death. Discrimination of the 5-year prediction was based on Cox models using Harrell's concordance index (c-index). RESULTS: A total of 111 patients had DE (39%), NCCN-IPI (8%), and disease progression (46%). The NCCN-IPI adjusted HR of DE was 1.6 (95% confidence interval [CI]: 0.9-2.8; P = 0.117). The baseline NCCN-IPI c-index was 0.63. Adding DE to the NCCN-IPI slightly increased Harrell's concordance index (c-index) to 0.66 (P = 0.119). CONCLUSIONS: Adding DE to the NCCN-IPI may not improve the prognostic value to an acceptable level in resource-limited settings. Multiple independent confirmatory studies from a large cohort of lymphoma registries have provided additional evidence for the clinical utility of DE.

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PURPOSE: The purpose of this study was to determine the prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma (DLBCL) and the prognostic value of them in the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) subgroups. METHODS: A total of 113 patients who underwent 18F-FDG PET/CT examination in our institution were retrospectively collected. The MTV was measured by iterative adaptive algorithm. The location of the lesion was obtained according to its three-dimensional coordinates, and Dmax was obtained. SDmax is derived from Dmax standardized by body surface area (BSA). The X-tile method was used to determine the optimal cut-off values for MTV, Dmax and SDmax. Cox regression analysis was used to perform univariate and multivariate analyses. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: The median follow-up time was 24 months. The median of MTV was 196.86 cm3 (range 2.54-2925.37 cm3), and the optimal cut-off value was 489 cm3. The median of SDmax was 0.25 m-1 (range 0.12-0.51 m-1), and the best cut-off value was 0.31 m-1. MTV and SDmax were independent prognostic factors of PFS (all P < 0.001). Combined with MTV and SDmax, the patients were divided into three groups, and the difference of PFS among the groups was statistically significant (P < 0.001), and was able to stratify the risk of NCCN-IPI patients in the low-risk (NCCN-IPI < 4) and high-risk (NCCN-IPI ≥ 4) groups (P = 0.001 and P = 0.031). CONCLUSION: MTV and SDmax are independent prognostic factors for PFS in DCBCL patients, which describe tumor burden and tumor dissemination characteristics, respectively. The combination of the two could facilitate risk stratification between the low-risk and high-risk NCCN-IPI groups.

Asunto(s)

Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Pronóstico , Carga Tumoral , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Medición de Riesgo , Fluorodesoxiglucosa F18

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BACKGROUND: Due to the rarity of PBL and the lack of large-scale studies, the prognostic value of IPI in PBL was controversial. Especially in the rituximab era, the ability of IPI to stratify prognosis in patients receiving immunochemotherapy was severely reduced. Then revised IPI (R-IPI) and National Comprehensive Cancer Network IPI (NCCN-IPI) were introduced. The present study aimed to evaluate the prognostic value of IPI and the other IPIs in patients with PBL in a Chinese population. METHODS: We performed a multicenter retrospective study of 71 patients with PBL from 3 institutions in China. The Kaplan-Meier method and log-rank tests were used for the survival analysis. Cox regression analysis was performed to evaluate the prognostic factors. Subgroup analysis was performed to assess the prognostic significance of IPI scores, R-IPI scores, and NCCN-IPI scores. RESULTS: The median follow-up was 4.7 years (0.7-21.8 years). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 90.2% and 96.3%. In the multivariate analysis, only IPI scores and radiotherapy were significantly associated with OS and PFS (P < 0.05). Applying the R-IPI in our patient cohort indicates a significant difference in PFS between the two groups of R-IPI (P = 0.034) but not for OS (P = 0.072). And the NCCN-IPI was prognostic for OS (P = 0.025) but not for PFS (P = 0.066). Subgroup analyses of IPI showed that survival analysis of IPI scores for the PFS and OS of patients using rituximab were not significantly different (P > 0.05). CONCLUSIONS: Our study confirms the prognostic value of IPI in patients with PBL, but the predictive value of IPI proved to be relatively low with the addition of the rituximab. The R-IPI and NCCN-IPI can accurately assess the high and low-risk groups of PBL patients but were insufficient to evaluate the intermediate risk group.

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BACKGROUND: This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients. METHODS: A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters' prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS). RESULTS: With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ2=30.179, P<0.001), and OS rates were 93.1%, 73.8%, 56.7%, and 43.3%, respectively (χ2=23.649, P<0.001), respectively. Compared with the NCCN-IPI alone, the revised risk model showed a stronger ability to reveal further discrimination among subgroups, especially for participants with very unfavorable survival outcomes (PFS: χ2=9.963, P=0.002; OS: χ2=4.166, P=0.041, respectively). CONCLUSIONS: The TLG, cell-of-origin subtypes, and NCCN-IPI are independent prognostic survival factors in DLBCL patients. Moreover, the revised risk model composed of the number of risk factors (high TLG, non-GCB, and high NCCN-IPI) can stratify patients better than the NCCN-IPI, especially for patients at high risk, which suggests its potential integration into decision making for personalized medicine.

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The discriminative power of International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL) decreased with the addition of rituximab to chemotherapy. The National Comprehensive Cancer Network (NCCN)-IPI and the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI were developed to improve the risk prediction for DLBCL patients. We aim to validate the NCCN-IPI and GELTAMO-IPI in a large and homogeneous cohort of 337 DLBCL patients treated with curative intent with R-CHOP/R-CHOP-like immunochemotherapy. The IPI stratifies patients in two independent risk groups and the estimated 5-year overall survival (OS) of the high-risk (HR) group was 43%. NCCN-IPI discriminated four risk groups and GELTAMO-IPI three risk groups of patients. The predicted 5-year OS of the HR group was 38% and 29%, respectively. NCCN-IPI and GELTAMO-IPI are more accurate prognostic indices than IPI in DBLCL patients treated with immunochemotherapy. GELTAMO-IPI demonstrated enhanced discrimination than NCCN-IPI for the higher-risk population.

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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico , Vincristina/uso terapéutico

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BACKGROUND: Aberrant MYC and BCL2 expression, cell of origin (COO), and National Comprehensive Cancer Network international prognostic index (NCCN-IPI) are commonly used for risk assessment and treatment decision in patients with diffuse large B-cell lymphoma (DLBCL). Although obesity has been shown to be of predictive value in DLBCL patients, it remains unclear whether it retains its prognostic relevance after those aforementioned novel factors being taken into consideration. METHODS: Patients with DLBCL were identified retrospectively in a single institute and data were collected through electronic databases and pharmacy records. RESULTS: Fifteen (17.6%) out of the 85 patients with DLBCL in our cohort were categorized as obese. They had lower platelet counts, were younger and more likely to harbor either BCL2- or MYC-overexpressing tumors. The NCCN-IPI scores, COO, and other clinical parameters were not significantly different between obese and non-obese patients. In spite that obesity adversely affected the treatment response to immunochemotherapy, multivariate analysis showed that only NCCN-IPI risk categories [hazard ratio (HR) 2.83 for high-intermediate or high-risk, versus low-intermediate or low-risk, P=0.034] and BCL2/MYC expressional status (HR 4.12 for BCL2high and/or MYChigh, versus both low expressors, P=0.004) independently predicted progression-free survival (PFS) outcome, whereas obesity lost its prognostic value in this regard (HR 1.81 for obese patients, P=0.242). Similarly, high-intermediate to high NCCN-IPI risk (HR 3.11, P=0.034) and increased expression in either BCL2 or MYC (HR 5.63, P=0.001) both portended an inferior overall survival (OS), but the presence of obesity did not affect the outcome (HR 1.65, P=0.352). CONCLUSIONS: Our study has demonstrated that, for the first time, obesity increases the frequency of BCL2- or MYC-overexpressing tumors in patients with DLBCL.

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BACKGROUND: Hemoglobin (Hgb) concentration at diagnosis is associated with outcome in cancer. In a recently reported simplified 3-factor prognostic score in Hodgkin lymphoma, Hgb, along with age and clinical stage, outperformed the classical International Prognostic Score with seven parameters. METHODS: In the present study, we investigated if pretherapeutic Hgb concentration added prognostic information to the NCCN-IPI in diffuse large B-cell lymphoma. We included patients from the Danish Lymphoma Registry (LYFO; N = 3499) and from the Molecular Epidemiology Resource (MER; N = 1225), Mayo Clinic and University of Iowa. Four sex-specific Hgb groups were defined: below transfusion threshold, from transfusion threshold to below lower limit of normal, from lower limit of normal to the population mean, and above the mean. We used multivariable Cox regression to estimate the hazard rate ratios (HR) and 95% CIs for overall survival (OS) and event-free survival (EFS), adjusting for sex, NCCN-IPI, comorbidity, and rituximab treatment. RESULTS: Approximately half of the patients had Hgb levels below the lower limit of normal. Compared to patients with Hgb levels above the mean, an inferior OS was directly correlated with lower pretreatment Hgb within the predefined groups (HR=1.23, HR=1.51, and HR=2.05, respectively). These findings were validated in the MER. CONCLUSION: Based on multivariable analysis, lower pretreatment Hgb, even within the normal range but below the mean, added prognostic information to established indices such as the NCCN-IPI and the Charlson comorbidity index.

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BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a poor prognostic indicator in various solid tumors. METHODS: We retrospectively analyzed 530 patients with de novo DLBCL who were diagnosed from April 2002 to November 2017. RESULTS: The median age of patients was 69 (range, 20-95) years, and 59% were male. The optimal cutoff for NLR was 5.2. NLR (5.2) was not associated with overall and progression free survival. CONCLUSION: Our study failed to reveal the predictive value of NLR and demonstrated that the NCCN-IPI might be the most powerful predictor in DLBCL.

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The identification of high-risk patients deserving alternative first-line treatments to R-CHOP is a research priority in diffuse large B cell lymphoma (DLBCL). Despite the increasing recognition of biological features underlying aggressive behavior, clinical scores remain the basis for prognostic evaluation and treatment stratification in DLBCL. We performed a retrospective analysis of patients with DLBCL uniformly treated with immunochemotherapy with the aim of assessing the discriminative power of the NCCN international prognostic index (IPI) and the GELTAMO-IPI scores in risk group stratification and compared them with the IPI. Additionally, we investigated if bulky disease, gender, beta-2 microglobulin (ß2m), body mass index, and B-symptoms have independent prognostic impact. We confirmed the discriminative ability of the three prognostic scores in terms of progression-free survival and overall survival and found that the NCCN-IPI performs better in the identification of a high-risk population compared to the IPI and the GELTAMO scores. In an attempt to improve the prognostic power of the NCCN-IPI we analyzed additional clinical variables. Bulky disease and elevated ß2m were found to be independent predictors of prognosis when controlling for the NCCN-IPI risk groups. However, they seem to bring no incremental power to the latter in the identification of poor outcome patients. We support the use of the NCCN-IPI for the clinical identification of high-risk patients in DLBCL. Future studies to unravel the biological heterogeneity within NCCN-IPI groups are needed to improve risk prediction and design targeted therapies for poor prognosis patients.

Asunto(s)

Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Selección de Paciente , Proyectos de Investigación , Microglobulina beta-2/sangre , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Factores Sexuales , Análisis de Supervivencia , Vincristina/uso terapéutico

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Linfoma de Células T Periférico/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Adulto Joven

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Low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. However, the association between cholesterol levels and diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of our study was to evaluate the prognostic value of serum lipid profile in DLBCL. Five hundred and fifty enrolled subjects with detailed serum lipid levels at diagnosis of DLBCL were randomly divided into a training set (n = 367) and a validation set (n = 183) (ratio, 2:1). Multivariate Cox regression analyses screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Performances of models were compared using C-index and area under the curve in internal and external validation. The results showed that decreased levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were associated with unfavorable PFS and OS in the rituximab era, and concurrently low HDL-C together with low LDL-C was an independent prognostic indicator for both PFS and OS. Patients achieving complete remission or partial remission after 6-8 circles of chemotherapies had significantly increased cholesterol levels compared to the levels at DLBCL diagnosis, and HDL-C or LDL-C elevations were correlated with better survival. Furthermore, the predictive and discriminatory capacity of the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) together with low cholesterol levels was superior to NCCN-IPI alone both in the training and validation set. In conclusion, serum cholesterol levels are simple and routinely tested parameters, which may be good candidates for predicting prognosis in the future clinical practice of DLBCL.

Asunto(s)

Colesterol/sangre , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/patología , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico

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The prognostic value of the International Prognostic Index (IPI) has been re-evaluated in the rituximab-treated diffuse large B cell lymphoma (DLBCL) patients. Accordingly, National Comprehensive Cancer Network-IPI (NCCN-IPI) has been introduced to estimate prognosis of DLBCL patients. However, comorbidities that frequently affect elderly DLBCL patients were not analyzed. The aim of this study was to evaluate the prognostic significance of comorbidities using Charlson Comorbidity Index (CCI) in 962 DLBCL patients. According to CCI, majority of patients (73.6%) did not have any comorbidity, while high CCI (≥ 2) was observed in 71/962 (7.4%) patients, and in 55/426 (12.9%) of the elderly patients aged ≥ 60 years. When the CCI was analyzed in a multivariate model along with the NCCN-IPI parameters, it stood out as a threefold independent risk factor of a lethal outcome. Also, we have developed a novel comorbidity-NCCN-IPI (cNCCN-IPI) by adding additional 3 points if the patient had a CCI ≥ 2. Four risk groups emerged with the following patient distribution in low, low-intermediate, high-intermediate, and high group: 3.4, 34.3, 49.4, and 12.5%, respectively. The prognostic value of the new cNCCN-IPI was 2.1% improved compared to that of the IPI, and 1.3% improved compared to that of the NCCN-IPI (p < 0.05). This difference was more pronounced in elderly patients, in whom the cNCCN-IPI showed a 5.1% better discriminative power compared to that of the IPI, and 3.6% better compared to the NCCN-IPI. The NCCN-IPI enhanced by the CCI and combined with redistributed risk groups is better for differentiating risk categories in unselected DLBCL patients, especially in the elderly.

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Protocolos de Quimioterapia Combinada Antineoplásica , Asma/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hipertiroidismo/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/mortalidad , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Comorbilidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/epidemiología , Hipertiroidismo/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia

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Positron emission tomography-computed tomography (PET-CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET-CT. We validated the prognostic value of CR by PET-CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and cell of origin (COO) to patients with CR by PET-CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET-CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET-CT and 71 patients by CT only. Patients with CR by PET-CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN-IPI had a dismal outcome despite achieving CR by PET-CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET-CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET-CT was a better predictor of survival outcomes than CR by CT only. The NCCN-IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET-CT.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/metabolismo , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificación

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Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Asunto(s)

Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Microglobulina beta-2/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia

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BACKGROUND: The International Prognostic Index (IPI) has been a useful tool for predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Herein, we aimed to develop a new prognostic model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: Between March 2004 and June 2012, patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy regimen were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and secondary endpoints were a new prognostic index for DLBCL and validation of the National Comprehensive Cancer Network-International Prognostic Index in our cohort, respectively. RESULTS: The AMC cohort comprised 621 patients. The median follow-up duration was 43.3 months (range, 6.2-122.5 mo). Univariate analysis revealed that age (≤60 vs. >60 yr), lactate dehydrogenase (LDH; within normal vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 or 1 vs. ≥2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≤1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin (ß2MG, ≤2.5 vs. >2.5) can be used to predict overall survival (OS). In multivariate analysis, only age, LDH, ECOG performance status, and ß2MG were significantly associated with OS, and we developed a new prognostic model with these 4 factors. The new prognostic model showed better discriminative power compared with the classic IPI. CONCLUSION: Our new prognostic index model for DLBCL in the rituximab era has good discriminative power and is convenient to use.

RESUMEN

BACKGROUND: The International Prognostic Index (IPI) has been a useful tool for predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Herein, we aimed to develop a new prognostic model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: Between March 2004 and June 2012, patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy regimen were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and secondary endpoints were a new prognostic index for DLBCL and validation of the National Comprehensive Cancer Network-International Prognostic Index in our cohort, respectively. RESULTS: The AMC cohort comprised 621 patients. The median follow-up duration was 43.3 months (range, 6.2–122.5 mo). Univariate analysis revealed that age (≤60 vs. >60 yr), lactate dehydrogenase (LDH; within normal vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 or 1 vs. ≥2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≤1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin (β2MG, ≤2.5 vs. >2.5) can be used to predict overall survival (OS). In multivariate analysis, only age, LDH, ECOG performance status, and β2MG were significantly associated with OS, and we developed a new prognostic model with these 4 factors. The new prognostic model showed better discriminative power compared with the classic IPI. CONCLUSION: Our new prognostic index model for DLBCL in the rituximab era has good discriminative power and is convenient to use.

Asunto(s)

Humanos , Linfocitos B , Estudios de Cohortes , Ciclofosfamida , Doxorrubicina , Quimioterapia , Estudios de Seguimiento , L-Lactato Deshidrogenasa , Linfoma , Linfoma de Células B , Linfoma no Hodgkin , Análisis Multivariante , Prednisolona , Pronóstico , Rituximab , Vincristina

RESUMEN

To evaluate the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI), we analyzed 284 patients treated with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in our institution in Japan. Their 5-year overall survival (OS) by risk level was 80.7%, 74.8%, 55.4% and 67.5% (P=0.005); and their 5-year progression-free survival (PFS) was 76.8%, 78.6%, 63.7% and 58.3% (P=0.0722). The NCCN-IPI is a simple scale that uses conventional clinical factors, but did not reflect survival in our cohort. The NCCN-IPI may require further evaluation for different regions and ethnicities before adopting it for routine clinical use.

RESUMEN

The recently devised National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) appears superior to the revised IPI (R-IPI) in delineating outcome in diffuse large B-cell lymphoma. We examined the outcome of a population-based cohort of 223 consecutive patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOP-like immuno-chemotherapy between January 2005 and December 2011 by both the NCCN-IPI and R-IPI, and further stratified outcome by the achievement of both computerized tomography (CT) and positron emission tomography (PET)-CT complete remission (CR), with the latter reassessed using blinded central review by an independent nuclear medicine and radiology specialist. The NCCN-IPI was superior to the R-IPI in identifying patients at very high risk of systemic and/or central nervous system relapse. Notably, both the NCCN-IPI and the R-IPI remained strongly predictive of relapse irrespective of CT or PET-defined remission status following R-CHOP. Patients with high-risk NCCN-IPI scores (≥6) have a dismal outcome following R-CHOP therapy regardless of PET-defined response to R-CHOP. Moreover, such patients appear refractory to salvage chemotherapy and thus require alternative therapeutic approaches, although age and performance status may, for many patients, preclude the safe delivery of a primary intensified regimen. By contrast, patients with NCCN-IPI 1-5 who achieve PET-CR following R-CHOP have excellent outcomes and may merit reduced follow up frequency.

Asunto(s)

Linfoma de Células B Grandes Difuso/diagnóstico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Tomografía de Emisión de Positrones/métodos , Prednisona/uso terapéutico , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto Joven

RESUMEN

Diffuse large B cell lymphoma (DLBCL) affects more commonly patients over 60 years. These patients have vast number of comorbidities which can modify survival as well as other clinical parameters. The aim of this study was to evaluate prognostic significance of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), absolute lymphocyte count (ALC), absolute monocyte count (AMC), lymphocyte-to-monocyte ratio (LMR) and comorbidities expressed with Charlson Comorbidity Index (CCI). A total of 182 DLBCL patients 60 years old and older were included, focusing on whole group and patients older than 70. All patients were treated with immunochemotherapy.Overall treatment response was achieved in 84.6% of patients. The NCCN-IPI was of highly prognostic value in the analyzed group (p<0.0001). Survival analysis showed that ALC>1.1x109/L, AMC≤0.59x109/L, and LMR>2.8 were associated with more favorable outcome (p=0.029, p=0.019, p=0.028, respectively). The patients with CCI≥2 had poorer outcome (p=0.008) compared to the patients with CCI 0-1. Multivariate analysis showed that among ALC, AMC, LMR, NCCN-IPI and CCI, the NCCN-IPI was the critical parameter that significantly affected survival (p<0.0001). Furthermore, comorbidities were also valuable independent factors which influenced survival (p=0.031) as well as the ALC (p=0.024). In elderly DLBCL patients, NCCN-IPI and ALC proved their prognostic validity, while poorer outcome could be expected in older patients with high CCI (≥2). Furthermore, mentioned prognostic parameters retained their prognostic value in the group of patients older than 70.