Role of Bone Marrow Infiltration and POD 24 in Follicular Lymphoma

Abstract Follicular lymphoma (FL) is the most common indolent lymphoma with a median survival approaching 20 years. However, there is significant clinical heterogeneity with subsets of patients experiencing transformation, early recurrence or refractory disease. Some authors found that progression of disease within 24 months of diagnosis, in patients treated with chemoimmunotherapy (POD24), is associated with poor overall survival (OS). OBJECTIVE Evaluate the POD24 as an early clinical endpoint in FL and evaluate FL international prognostic index (FLIPI), and other baseline risk factors at diagnosis for overall survival and relapse. METHODS We conducted a retrospective and observational study in which 160 patients with follicular lymphoma who received R-CHOP at National Institute of Cancerology, Mexico from 2011 to 2017. We analyze with Kaplan Meier curves, log rank test and logistic regression model. RESULTS We analyze 160 patients, median of age was 53 years (26- 88), with a female : male ratio of 1.17:1. In this group: 86% had hemoglobin >12 mg/dL, LDH was normal in 62%, 1-4 nodal areas were affected in 64%, 56% of patients had high FLIPI score, 27% had B symptoms and we found bone marrow infiltration in 30% of cases; grade 2 Follicular lymphoma was the most common histological subtype (40.5%). Most of patients achieved complete response (81%), 12% partial response after the first line therapy. Only 13 patients (8%) presents relapse. Sixty four percent received maintenance. Only 13 of patients relapsed, 10 after 24 months and only 3 in first 24 months from diagnostic (POD 24). Fig. 1 Overall survival in our population was 89% to 8 years, the factors with statistical significance in the bivariate analysis were the more nodal regions affected (1-4), high FLIPI score and POD 24 POD 24, adjusted to FLIPI score, was an independent predictor of survival in regression analysis (p<0.041, HR:35 IC 95% 1.15-1060.21). The bone marrow infiltration at diagnosis was the only independent predictor for relapse (p<0.007, HR: 6.9, IC 95% 1.7- 28.2). CONCLUSION: In our study group, POD 24, was an important predictor of overall survival, and bone marrow infiltration at diagnosis was the only predictor factor for relapse. Disclosures No relevant conflicts of interest to declare.

Download Full-text

BONE MARROW IN FOLLICULAR LYMPHOMA PROGNOSIS

Russian Journal of Biotherapy ◽

10.17650/1726-9784-2016-15-3-99-102 ◽

2016 ◽

Vol 15 (3) ◽

pp. 99-102 ◽

Cited By ~ 1

Author(s):

N. N. Tupitsyn ◽

N. A. Falaleeva ◽

A. V. Mozhenkova ◽

A. I. Pavlovskaya

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Follicular Lymphoma ◽

Histological Study ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

Prognostic Role ◽

Long Time

Background. Bone marrow is the mostfrequent metastatic site in follicular lymphoma, 40-70 % cases. It’s unfovourable prognostic role is stated in the index FLIPI-2 (Follicular Lymphoma International Prognostic Index-2). Objective. To study both prognostic role of bone marrow involvement and it’s relation to erythropoiesis peculiarities in follicular lymphoma was the purpose of this research. Materials and methods. Histological study was performed in 269 follicular lymphoma patients. Erythropoiesis peculiarities were studied in that patients according to standard myelogram analysis. Results. Bone marrow involvement was noted according to trephine biopsy section staining in 37,9 % of follicular lymphoma case (102 from 269). Bone marrow involvement did not influenced the prognosis (overall survival) in all period of observation (p = 0,18). Longterm survival (more than 48 months) was negatively influenced by bone marrow involvement (p = 0,04). Intertrabecular pattern of follicular lymphoma growth in bone marrow was negative prognostic factor (p = 0,02). We noted negative correlation between bone marrow involvement and the elevation of orthochromic normoblasts in bone marrow of patients with follicular lymphoma. In cause of bone marrow such elevation was noted in 67 %, and in the absense of involvement - in 78 % (p = 0,043). Elevation of orthochromic normoblasts did not influenced the overall survival of follicular lymphoma patients (p = 0,89). Conclusion. Bone marrow involvement in follicular lymphoma plays prognostically unfavourable role in long-time observation periods (later than 48 months). The most unfavourable are the intertrabecular patchy lesions. Involvement of bone marrow is in opposite relations to elevation of orthochromic normoblast, but the latter sign is of no prognostic significance.

Download Full-text

High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma

Blood ◽

10.1182/blood-2006-04-018218 ◽

2006 ◽

Vol 108 (9) ◽

pp. 2957-2964 ◽

Cited By ~ 342

Author(s):

Joaquim Carreras ◽

Armando Lopez-Guillermo ◽

Bridget C. Fox ◽

Lluis Colomo ◽

Antonio Martinez ◽

...

Keyword(s):

Overall Survival ◽

T Cells ◽

Regulatory T Cells ◽

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

Specific Cell ◽

First Relapse ◽

The Impact

Abstract The tumor microenvironment plays an important role in the biologic behavior of follicular lymphoma (FL), but the specific cell subsets involved in this regulation are unknown. To determine the impact of FOXP3-positive regulatory T cells (Tregs) in the progression and outcome of FL patients, we examined samples from 97 patients at diagnosis and 37 at first relapse with an anti-FOXP3 monoclonal antibody. Tregs were quantified using computerized image analysis. The median overall survival (OS) of the series was 9.9 years, and the FL International Prognostic Index (FLIPI) was prognostically significant. The median Treg percentage at diagnosis was 10.5%. Overall, 49 patients had more than 10% Tregs, 30 between 5% to 10%, and 19 less than 5%, with a 5-year OS of 80%, 74%, and 50%, respectively (P = .001). Patients with very low numbers of Tregs (< 5%) presented more frequently with refractory disease (P = .007). The prognostic significance of Treg numbers was independent of the FLIPI. Seven transformed diffuse large B-cell lymphomas (DLBCLs) had lower Treg percentages (mean: 3.3%) than FL grades 1,2 (mean: 12.1%) or 3 (mean: 9%) (P < .02). In conclusion, high Treg numbers predict improved survival of FL patients, while a marked reduction in Tregs is observed on transformation to DLBCL.

Download Full-text

Follicular lymphoma patients with a high FLIPI score and a high tumor burden: A risk stratification model

Vojnosanitetski pregled ◽

10.2298/vsp1501026a ◽

2015 ◽

Vol 72 (1) ◽

pp. 26-32 ◽

Cited By ~ 2

Author(s):

Bosko Andjelic ◽

Milena Todorovic-Balint ◽

Darko Antic ◽

Jelena Bila ◽

Vladislava Djurasinovic ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Prognostic Factors ◽

Follicular Lymphoma ◽

Histological Grade ◽

International Prognostic Index ◽

Prognostic Index ◽

Tumor Burden ◽

Cox Regression Analysis ◽

High Tumor Burden

Background/Aim. The widely accepted Follicular Lymphoma International Prognostic Index (FLIPI) divides patients into three risk groups based on the score of adverse prognostic factors. The estimated 5-year survival in patients with a high FLIPI score is around 50%. The aim of this study was to analyse the prognostic value of clinical and laboratory parameters that are not included in the FLIPI and the New Prognostic Index for Follicular Lymphoma developed by the International Follicular Lymphoma Prognostic Factor Project (FLIPI2) indices, in follicular lymphoma (FL) patients with a high FLIPI score and high tumor burden. Methods. The retrospective analysis included 57 newly diagnosed patients with FL, a high FLIPI score and a high tumor burden. All the patients were diagnosed and treated between April 2000 and June 2007 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade. Results. The patients with a histological grade > 1, erythrocyte sedimentation rate (ESR) ? 45 mm/h and hypoalbuminemia had a significantly worse overall survival (p = 0.015; p = 0.001; p = 0.008, respectively), while there was a tendency toward worse overall survival in the patients with an Eastern Cooperative Oncology Group (ECOG) > 1 (p = 0.075). Multivariate Cox regression analysis identified a histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia as independent risk factors for a poor outcome. Based on a cumulative score of unfavourable prognostic factors, patients who had 0 or 1 unfavourable factors had a significantly better 5-year overall survival compared to patients with 2 or 3 risk factors (75% vs 24.1%, p = 0.000). Conclusion. The obtained results suggest that from the examined prognostic parameters histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia can contribute in defining patients who need more aggressive initial treatment approach, if two or three of these parameters are present on presentation.

Download Full-text

Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models

Blood Advances ◽

10.1182/bloodadvances.2020002546 ◽

2020 ◽

Vol 4 (18) ◽

pp. 4451-4462

Author(s):

Stefan Alig ◽

Vindi Jurinovic ◽

Mohammad Shahrokh Esfahani ◽

Sarah Haebe ◽

Verena Passerini ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

Statistical Significance ◽

International Prognostic Index ◽

Prognostic Index ◽

Risk Scores ◽

High Dose ◽

Risk Models ◽

Progression Of Disease ◽

Risk Patients

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months–prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.

Download Full-text

An Enhanced International Prognostic Index (IPI) for Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in the Rituximab Era Using the National Comprehensive Cancer Network (NCCN) Database.

Blood ◽

10.1182/blood.v120.21.2656.2656 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2656-2656

Author(s):

Zheng Zhou ◽

Alfred W. Rademaker ◽

Leo I. Gordon ◽

Ann S. LaCasce ◽

Ann Vanderplas ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

High Risk ◽

International Prognostic Index ◽

Model Development ◽

Prognostic Index ◽

Risk Groups ◽

Ratio Test ◽

Validation Sample ◽

Gi Tract

Abstract Abstract 2656 Introduction: The International Prognostic Index (IPI) was first developed in 1993 to risk stratify patients with aggressive Non-Hodgkin's lymphoma (NHL) for outcome prediction (Shipp, NEJM, 1993). Since the addition of rituximab to conventional CHOP chemotherapy for the treatment of DLBCL, there have been many efforts to validate the IPI as well as to improve upon the model's capacity to distinguish subgroups with discrete clinical outcomes, especially high-risk patients. Previous studies have focused on adding clinical or biologic prognostic factor(s) to the original model or regrouping the original IPI score (R-IPI; Sehn, Blood, 2007). We, therefore, built anew a modern IPI based solely on clinical factors available in the real world NCCN clinical database. Methods: Using the nationwide population-based NHL lymphoma database from NCCN, patients with newly diagnosed DLBCL enrolled between June 2000 and Dec. 2010 at 7 NCCN cancer centers were included with at least 1 year and up to 5 years of follow-up. Clinical characteristics including age, Ann Arbor stage, ECOG performance status, disease in extranodal sites (including positivity in bone marrow, CNS, liver/GI tract, lung, other sites and spleen), LDH, presence of bulky disease (>10 cm) as well as B symptoms were studied as potential predictors for model development using COX proportional hazards regression. IPI scores were assigned proportionally based on parameter estimates of the statistically significant predictors in the final COX model. Model selection and its comparison to the original IPI model were made based on Akaike Criteria (AIC) and the likelihood ratio test. Categorization of age and LDH was decided by testing the linearity assumption and Martingale residuals. Kaplan-Meier curves were plotted for stratified risk groups per the new and original IPI. Finally, both IPI models were compared using the initial randomly selected 15% validation sample. Results: There were 1,650 DLBCL patients with complete clinical information included for model development. The new IPI model consisted of similar component predictors but used a maximum of 8 scoring points by further categorizing age group into >40–60 (score of 1), >60–75 (score of 2) and >75 yrs (score of 3), and normalized LDH between >1–3 times (score of 1) and 33 times (score of 2) upper limit of normal. These categorizations minimized the Martingale residuals. Age effect was linear and 20-year increments fit the model best, whereas the effect of normalized LDH was not linear and reached plateau at a ratio of 3. Lymphomatous involvement either of bone marrow, CNS, Liver/GI tract or lung appeared as a stronger predictor (p<0.001) than number of extranodal sites (p=0.91). Four risk groups (Low, Low-intermediate, High-intermediate and High) were identified using the current IPI (Table 1) with enhanced discrimination power when compared with the original IPI and better global model fitting statistics, i.e. smaller AIC and significant likelihood ratio test (p<0.001). It was possible to identify a high risk group (score 3 6) with 5-year overall survival of 33% (95% CI: 22%–45%). Better model prediction was also shown in the validation sample. Conclusions: We were able to develop an enhanced IPI model for clinical prediction among previously untreated DLBCL cases by using patient level data from the NCCN NHL database. The NCCN-IPI demonstrates better risk stratification and identifies a poor risk subgroup with <50% 5-year overall survival in the current real-world clinical setting as compared to the original IPI model developed for aggressive lymphoma prior to the rituximab era. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

The Clinical Impact of Minimal Bone Marrow Involvement on the Outcome of Patients with Follicular Lymphoma

Blood ◽

10.1182/blood.v128.22.2966.2966 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2966-2966

Author(s):

Daisuke Kato ◽

Satoshi Yoshioka ◽

Tomohiro Yabushita ◽

Yoshimitsu Shimomura ◽

Yuichiro Ono ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

Prognostic Index ◽

Morphological Evidence ◽

Stage Disease ◽

Igh Rearrangement ◽

The Impact ◽

Index Table

Abstract Introduction: Follicular lymphoma (FL) is the second most common type of non-Hodgkin cell lymphoma, and usually manifests as a disseminated disease. Bone marrow (BM) involvement, which occurs in 40-70% of cases, is often seen in follicular lymphoma and thought to be associated with less favorable prognosis. Diagnosis of BM involvement has traditionally been based on morphological findings, and BM involvement has been determined using histology alone in most clinical trials. Immunocytologic or molecular studies, such as flow cytometry (FCM) and polymerase chain reaction (PCR), have become more readily available, and their usage has clearly documented minimal BM involvement reproducibly. In this study, we evaluated the impact of BM involvement detected by FCM and PCR on the outcome of patients treated for FL. Methods: Patients who were diagnosed with biopsy-proven FL between 2004 and 2015 at our institution were included in the study. All patients had received a staging bone marrow examination before treatment with immunotherapy-based regimen. Immunocytologic [FCM] and/or molecular [PCR] studies were always performed if the patients did not have morphological BM involvement. We used 4- or 6- color FCM, and performed PCR analysis of Bcl-2/IgH rearrangement and/or IgH rearrangement detected by modified BioMed-2 protocol. A total of 90 patients were included, and the median follow-up duration was 36 months (range, 6|122 months). The BM status was classified using into 3 categories: morphological, minimal, and negative BM involvement. Minimal BM involvement was defined as BM involvement detected by FCM or PCR without morphological evidence. Morphological and minimal BM involvements were detected in 37 (41%) and 38 (42%) patients, respectively. The primary outcome measure was progression-free survival (PFS). PFS curves were plotted using the Kaplan-Meier method and compared by the log-rank test. Multivariate analyses were performed using a Cox linear regression model. There were significant differences in gender, LDH levels, stage, nodal sites, and FL International Prognostic Index (FLIPI) between patients with and without morphological BM involvement (Table1). Results: The 3-year PFS rate for patients with negative BM involvement was significantly better than that for patients with minimal or morphological BM involvement (84.8% vs. 40.3% vs. 60.5%; p= 0.043) (Figure 1). There was no statistical difference in 3-year PFS between patients with morphological BM involvement and those with minimal BM involvement. The difference of 3-year PFS rate between patients with minimal BM involvement and those with negative BM involvement was significant for patients with FLIPI low-intermediate risk (88.9% vs. 51.5%; p= 0.032) and those with advanced stage disease (90.0% vs. 33.6%; p= 0.027), but there were no significant differences in patients deemed FLIPI high risk and those with limited stage disease. Multivariate analysis revealed that BM involvement, including morphological and minimal involvement, was a significant poor prognostic factor (hazard ratio 4.885 [95% confidence interval 1.16-20.56], p = 0.0305). Conclusion: At the start of treatment, bone marrow involvement was seen in most FL patients. Patients without any BM involvement had an excellent prognosis. Patients with minimal BM involvement had an equally poor prognosis as those with morphologic BM involvement. Table 1 FLIPI: Follicular Lymphoma International Prognostic Index Table 1. FLIPI: Follicular Lymphoma International Prognostic Index Table 2 BM state positive: including morphological and minimal bone marrow involvement. Table 2. BM state positive: including morphological and minimal bone marrow involvement. Figure Figure. Disclosures Ishikawa: Mundipharma KK: Research Funding.

Download Full-text

Uninvolved Immunoglobulin Suppression Determined By "Hevylite" ASSAY. Strongly Predicts Evolution of Smoldering Myeloma (SMM) to Symptomatic Multiple Myeloma (MM)

Blood ◽

10.1182/blood-2018-99-118631 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5584-5584

Author(s):

Paraskevi Papaioannou ◽

Annita Ioanna Gkioka ◽

Kallirroi Tsalimalma ◽

Aspasia Koudouna ◽

Anastasia Kopsaftopoulou ◽

...

Keyword(s):

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Rapid Evolution ◽

Great Majority ◽

Bone Marrow Infiltration ◽

Prognostic Information ◽

Increased Risk

Abstract SMM may have an indolent course and remain stable for years; however, some patients evolve to MM requiring treatment within two years or less. To timely recognize these patients, three biomarkers (FLCR>100, ≥1 osteolysis and ≥60% plasma cell bone marrow infiltration) were recently established to discriminate asymptomatic MM patients at increased risk of rapid evolution and therefore, patients displaying the aforementioned biomarkers are considered symptomatic and receive immediate treatment. Despite the usage of the new IMWG definition criteria, there are still patients evolving rapidly and the notion of High risk SMM remains subjective among scientific groups. We herein studied wherever immunoglobulin (Ig) Heavy/Light Chain (HLC) measurements with the "Hevylite" assay that measures separately HLC-IgA, -G, -M-kappa or lambda, could add prognostic information on SMM evolution, with special attention to the significance of polyclonal Ig suppression. This method allows exact quantification of the amount of pure monoclonal fraction but also the degree of suppression of uninvolved polyclonal Igs. Patients and Methods: We studied 79 SMM patients of whom 30 were men and 49 women, with median age 65 (31-84) Ig type was IgG in 64 patients (81%) and IgA in the rest (19%). None of the patients had a free light chain ratio (FLCR) of more than 100, bone disease or more than 60% plasma cell bone marrow infiltration, in accordance to the last IMWG definition criteria. Patients were regularly followed (each 3 months) since SMM diagnosis and for a long period of time (median 98 months) during which 15 patients evolved to MM. "HevyLite" assay measurements were performed by nephelometry according to the manufacturer's instructions in frozen sera sample drawn at the time of diagnosis. We then calculated in all patients the ratio of involved/uninvolved Ig (HLCR); we also scored on a 5 points scale the eventuality of uninvolved Ig kappa or lambda below normal limits, that are, according to the manufacturer's testing on healthy individuals, 3608, 2023, 300, 312, 267, and 185 mg/L for IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda, IgM-kappa and IgM-lambda respectively. Results' relationship with SMM evolution were analyzed by standard methods using the SPSS v22.0. software and p values below 0,05 were considered statistically significant. Survival curved were drawn according to Kaplan-Mayer method. Results: Monoclonal Ig type was IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda in 61%, 19%, 11% and 9% of SMM patients respectively. Uninvolved IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda, IgM-kappa, IgM-lambda ranged from 625 to 14300 mg/L, 495 to 12700 mg/L , 214 to 2930 mg/L, 38 to 2580 mg/L, 19 to 1300 mg/L, 51 to 950 mg/L respectively. Median HLCR was 7 (range 0,24-707). Patients with HLCR above median tended to evolve faster than the others (p=0,1-not reaching statistical significance). Thirty-five patients had no one uninvolved Ig class depressed (score 0), 28 had 1, 9 had 2, 5 had 3 and 2 had 4; No score 5 was observed. Time to evolution strongly correlated to high score uninvolved Ig suppression (p< 0,00001). A simplified score separating 3 groups, the first with 0 Ig suppression, the 2nd with 1 or 2 and the 3rd with 3 or 4 proved to be equally potent in separating 3 risk-groups of SMM patients at risk of evolution to myeloma (p< 0,00001) and the great majority of the patients in the 3rd group evolved within two years (figure). In conclusion, the presence of decreased uninvolved Ig levels as determined by "Hevylite" constitutes a powerful prognostic marker of SMM evolution to MM. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Retrospective Analysis of Treatment Outcomes for Patients with Follicular Lymphoma and Comorbidities

Blood ◽

10.1182/blood.v126.23.5082.5082 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5082-5082

Author(s):

Aya Watanabe ◽

Yoichi Imai ◽

Kenjiro Mitsuhashi ◽

Akihito Shinohara ◽

Norina Tanaka ◽

...

Keyword(s):

Decision Making ◽

Overall Survival ◽

Liver Disease ◽

Follicular Lymphoma ◽

Charlson Comorbidity Index ◽

Clinical Characteristics ◽

International Prognostic Index ◽

Prognostic Index ◽

Chop Regimen ◽

Comorbidity Index

Abstract Follicular lymphoma (FL) is a low-grade B-cell lymphoma, and the response of FL to treatment, as well as progression-free survival and overall survival (OS), are improved by the application of combined chemotherapy with rituximab (R). The cyclophosphamide, adriamycin, vincristine, and prednisolone with rituximab (R-CHOP) regimen is the standard first-line therapy for patients with FL. However, many patients have coexistent diseases (comorbidities), and it is believed that therapeutic decision-making is influenced by comorbidities. In this study, we retrospectively analyzed treatment decision-making and its outcome for patients with FL. Based on this analysis, we investigated how the presence of comorbidity affects the survival of patients with FL. We analyzed 113 patients who were diagnosed with FL at our institute between September 2001 and March 2014. The treatment strategy was classified as observation without treatment, chemotherapy, radiotherapy, and others. Chemotherapy was subclassified as R-CHOP, reduced R-CHOP (the chemotherapeutic dose was reduced), and other chemotherapy. The severity of the comorbidity present at the time of diagnosis of FL was estimated according to the Charlson Comorbidity Index (CCI) (Table 1). The clinical characteristics of the 113 patients are shown in Table 2. The median age of the patients was 60 years. Six patients were observed without treatment, and 8 patients underwent resection or localized radiation for lymphoma. R-CHOP and other chemotherapy regimens were utilized in 84, and 15 patients, respectively. The 5-year OS rates of patients treated with R-CHOP, reduced R-CHOP, and other chemotherapy regimens were 92.3%, 75.5%, and 74.1%, respectively. As shown in a previous study (Andre Wieringa, et al., Br J Haematol, 2014, 165, 489-496), the 5-year OS rate of patients with CCI score ≥2 was inferior to that of patients with CCI 0-1 (CCI ≥2 (n = 32); 76.5%, CCI 0-1(n=81); 92.4%, p = 0.0361, Figure 1a). When we analyze the patients treated with R-CHOP, the overall response rate was 92.4% (complete response [CR] = 77.2%, partial response [PR] = 15.1%) in patients with a CCI score of 0-1 and 94.4% (CR = 77.8%, PR = 16.7%) in those with CCI score ≥ 2. In addition, there was no significant difference in the 5-year OS rate between patients with a CCI score of 0-1 or ≥2 (91.0% vs. 85.0%, p = 0.779, Figure 1b). Although, the percentage of patients with CCI ≥2 is lower than that of the other therapies (CCI ≥2; R-CHOP 25%, other chemotherapy 67%), it is supposed that R-CHOP is effective even if the patients have severe comorbidities. In 6 patients among these, treatment was discontinued or the chemotherapeutic dose was reduced due to myelosuppression during the designated course of therapy .The 5-year OS rate of these patients was favorable, even among those with high CCI score(CCI 0,1; 94.1%, CCI ≥2; 100%). Thus, it appears that R-CHOP with appropriate dose modification during the designated course will improve patient survival. Our results indicate that patients with severe comorbidities can be treated effectively by adjusting R-CHOP. Table 1. The items used to estimate the Charlson comorbidity index in each patient Comorbidity Score No. of patients Cardiac disease 1 5 Peripheral vascular disease 1 1 Cerebrovascular disease 1 3 Chronic pulmonary disease 1 6 Connective tissue disease 1 8 Ulcers 1 3 Mild liver disease 1 4 Diabetes 1 16 Tumors 2 22 Moderate or severe liver disease 3 1 Metastatic solid tumors 6 2 Table 2. Clinical characteristics of the patients Characteristic No. of patients (n = 113) Percentage (%) Sex Male 53 47 Female 60 53 Age >60 years 56 50 ≤60 years 57 50 IPI Low 55 49 Low-intermediate 38 34 High-intermediate 17 15 High 3 2 FLIPI Low 41 36 Intermediate 36 32 High 36 32 Therapy None 6 4 Resection only 3 3 Radiotherapy only 3 3 Resection and radiotherapy 2 2 R-CHOP 71 63 Discontinued or dose was reduced 23 20 Reduced R-CHOP 13 12 Other chemotherapy 15 13 IPI, international prognostic index; FLIPI, follicular lymphoma international prognostic index; R-CHOP, cyclophosphamide, adriamycin, vincristine, and prednisolone with rituximab Figure 1. Overall survival of patients treated with the cyclophosphamide, adriamycin, vincristine, and prednisolone with rituximab (R-CHOP) regimen according to the Charlson Comorbidity Index (CCI) Figure 1. Overall survival of patients treated with the cyclophosphamide, adriamycin, vincristine, and prednisolone with rituximab (R-CHOP) regimen according to the Charlson Comorbidity Index (CCI) Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Increasing Grades of Follicular Lymphoma Correlate with Better Prognosis in Patients Treated with Rituximab

Blood ◽

10.1182/blood.v118.21.1641.1641 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1641-1641

Author(s):

Björn Engelbrekt Wahlin ◽

Christer Sundström ◽

Harald Holte ◽

Birgitta Sander ◽

Bjørn Østenstad ◽

...

Keyword(s):

Lymph Nodes ◽

Follicular Lymphoma ◽

Conflicts Of Interest ◽

International Prognostic Index ◽

Prognostic Index ◽

World Health ◽

Time To Treatment Failure ◽

Immunologic Factors ◽

Health Organization ◽

Anti Cd20

Abstract Abstract 1641 Background: The World Health Organization (WHO) classification allocates indolent follicular lymphoma to grades 1, 2 or 3A according to the proportions of small centrocytes and large centroblasts in the neoplastic follicles. The prognostic value of the WHO's grading system in indolent follicular lymphoma has not been investigated in patients given the anti-CD20 monoclonal antibody rituximab without chemotherapy. Methods: We prospectively reviewed the follicular lymphoma grades in 276 grade 1–3A patients who received upfront rituximab without chemotherapy in two randomized trials. Flow cytometry analyses of malignant and nonmalignant lymphocyte subsets in lymph nodes and blood were also assessed. Results: In these patients given upfront rituximab-containing therapy, increasing grades of 1, 2, and 3A correlated with longer time to treatment-failure (P =0.002) and overall survival (P =0.045), independently of clinical factors (including the follicular lymphoma international prognostic index). The grades' impact was also independent of the levels of CD3+, CD4+, and CD8+ T cells in lymph nodes and in blood. Conclusion: Increasing grades of indolent follicular lymphoma correlate with better outcome in patients treated upfront with rituximab without chemotherapy, independently of clinical and immunologic factors. This suggests that treatment with rituximab acts differentially in tumors depending on the centrocyte/centroblast ratio. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Role of FDG-PET/CT in the Staging of Patients with Follicular Lymphoma

Blood ◽

10.1182/blood.v126.23.5010.5010 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5010-5010 ◽

Cited By ~ 1

Author(s):

Sayako Yuda ◽

Dai Maruyama ◽

Hiroaki Kurihara ◽

Akiko Miyagi Maeshima ◽

Kosuke Toyoda ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Fdg Pet ◽

International Prognostic Index ◽

Prognostic Index ◽

Response Assessment ◽

Bone Marrow Examination ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Introduction The Lugano Classification incorporating recommendations of 18-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) in the staging and response assessment of FDG-avid lymphomas was published. This classification is based on plenty of reports that suggested that evaluation with FDG-PET/CT improved the accuracy of the staging and response assessment of FDG-avid lymphomas, especially of diffuse large B-cell lymphoma and Hodgkin lymphoma. However, we are not sure of the role of FDG-PET/CT in indolent B-cell lymphomas, such as follicular lymphoma (FL). Patients and Methods Patients who were initially diagnosed as having FL of grade 1 to 3a at our institution between 2010 and 2012 were included in this study. We analyzed the number of nodal areas and the location of extranodal diseases identified by FDG-PET/CT added to the conventional evaluation consisting of CT, bone marrow examination and upper gastrointestinal endoscopy. The clinical stage by the conventional evaluation was compared to that by the Lugano Classification using FDG-PET/CT. It was also investigated whether adding PET/CT to the conventional evaluation might have had any influence on the decision regarding the initial treatment for patients with FL. Results A total of 67 patients with a median age of 62 years (range: 39-85) were included in this analysis. In comparison with CT, FDG-PET/CT identified a higher number of nodal areas in 11 patients (16%). Most of the extranodal sites except bone marrow and gastrointestinal tract were more frequently detected by PET-CT. Bone marrow examination detected 22 patients (33%) with bone marrow involvement, while PET-CT detected only 4 patients (6%). Gastrointestinal lesions were identified in 15 patients (22%) with conventional evaluation and in 4 patients (6%) by PET-CT (Table 1). In one of these 4 patients, endoscopic biopsy revealed that the PET-CT positive lesion was adenoma. In seven patients (10%), upstaging occurred through conventional evaluation plus PET-CT: 3 patients were upstaged from stage I to II, 2 from stage II to IV, 1 from stage II to III, and 1 from stage III to IV (Table 2). International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) were revised upward in 9 patients (13%) and 12 patients (18%), respectively. However, the change of stage, IPI, or FLIPI did not affect the decision regarding the initial treatment. Conclusion Our data suggest that FDG-PET/CT cannot take the place of the conventional evaluation, especially in patients with FL, because of the low sensitivity of involvements in bone marrow and gastrointestinal tract, although it may be helpful to use FDG-PET/CT in the staging of FL. Moreover, FDG-PET/CT might not have had any impact on the decision regarding the treatment strategy in FL. That may be partly because the lesions detected only by FDG-PET/CT did not affect the judgment of tumor burden. Prospective evaluation of the influence of FDG-PET/CT on the clinical outcomes is needed to establish an appropriate evaluation in the staging of patients with FL. Disclosures Maruyama: Takeda Pharmaceutical Company Limited: Honoraria; Eisai Co., Ltd.: Honoraria. Kobayashi:Nippon Shinyaku: Honoraria; Pfizer: Research Funding. Tobinai:Gilead Sciences: Research Funding.

Download Full-text