Prognostic Factors in Follicular Lymphoma Patients in Japan: Application of Follicular Lymphoma International Prognostic Index.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4702-4702
Author(s):  
Chizuko Hashimoto ◽  
Heiwa Kanamori ◽  
Naoto Tomita ◽  
Shin Fujisawa ◽  
Etsuko Yamazaki ◽  
...  

Abstract Background: By the new treatment approaches, such as anti-CD20 monoclonal antibody, purine analogues, high-dose therapy with SCT, the outcome of treatment for follicular lymphoma (FL) has been improved, but there is no consensus on any of these approaches except cases with early stage. Therefore, a reliable prognostic index would be needed in order to select the most appropriate treatment. Follicular Lymphoma International Prognostic Index (FLIPI) has recently been reported. We assessed characteristics at diagnosis and applied two prognostic models, the FLIPI and the IPI, to newly diagnosed Japanese patients (pts) with FL in this study. Methods: Response rate, overall survival (OS), and progression free survival (PFS) were calculated by the FLIPI and the IPI. For two prognostic models, 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, Hb<12.0g/dl, LDH>N, CS≥3, nodal sites>4), respectively. Results: Between 1988 and 2001, 107 pts of newly diagnosed FL (grade I-III) were analyzed. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. Initial therapy was CHOP-like regimen for 56 patients, ACOMP-B (the third generation regimen) for 44 patients, and another for 7 patients. The median follow-up of our series was 84 months (range 40–206 mo.). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 15 years was 64.4%, and median PFS at 15 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI. OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p<0.0001). PFS by the IPI and the FLIPI risk group at 10 year were L: 36%, LI: 23%, HI: 27%, H: 0% (p=0.0679), and L: 43%, I: 25%, H: 16% (p=0.0003). Correlation with a survival was recognized in FLIPI on OS, PFS more by significantly. In high-risk group of the FLIPI, PFS was significantly longer in pts treated with ACOMP-B, compared with pts treated with CHOP-like regimen (p=0.0015), and it tended to be better in OS, not so significant. Conclusions: The FLIPI is a promising consequence prediction model in follicular lymphoma in Japan. Standard treatment of FL is one of the most controversial issues. Outcome of CHOP were poor in high-risk group of the FLIPI, so to improve survival new treatment strategy is needed. The therapeutic strategy on the basis of different risks by reliable prognostic index, such as the FLIPI is necessary in future, in order to select the most appropriate treatment. As for grade 3, there was a little number of patients in our series, but further examination is necessary for adaptation of the FLIPI about this group.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4682-4682
Author(s):  
Chizuko Hashimoto ◽  
Heiwa Kanamori ◽  
Naoto Tomita ◽  
Maki Takabayashi ◽  
Etsuko Yamazaki ◽  
...  

Abstract By the new treatment approaches, such as rituximab, anti-CD20 radioimmunotherapy, high-dose therapy, transplantation, the outcome of treatment for follicular lymphoma has been improved. However, there are wide alternatives in a treatment of follicular lymphoma to stemcell transplantation from watchful waiting, and analysis of prognosis is important in choice of a therapy. The international non-Hodgkin’s lymphoma prognostic index (IPI) has been used for follicular lymphoma. Recently, a new method of the follicular lymphoma international prognostic index (FLIPI) is reported and attracts attention. We apply these two prognostic models for newly diagnosed follicular lymphoma, and reviewed its availability. 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, Hb<12.0g/dl, LDH>N, CS≥3, nodal sites>4), respectively. Between 1988 and 2001, 107 patients of newly diagnosed follicular lymphoma (grade I-III) were analyzed. Response rate, overall survival (OS), and progression free survival (PFS) were calculated for each prognostic model. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. The median follow-up of our series was 84 months (range 40–206 months). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 10 years was 64.4%, and median PFS at 10 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI. OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p<0.0001). PFS by the IPI and the FLIPI risk group at 10 year were L: 36%, LI: 23%, HI: 27%, H: 0% (p=0.0679), and L: 43%, I: 25%, H: 16% (p=0.0003). Correlation with a survival was recognized in FLIPI on OS, PFS more by significantly. As a conclusion, the FLIPI is a promising consequence prediction model. A standard treatment for follicular lymphoma is not established, and the examination that a treatment on the basis of prognosticator is strategic is necessary in future. As for grade 3, there was a little number of patients in this study, but further examination is necessary for adaptation of the FLIPI about this group.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 925-925 ◽  
Author(s):  
Christian Buske ◽  
Eva Hoster ◽  
Martin Dreyling ◽  
Joerg Hasford ◽  
Michael Unterhalt ◽  
...  

Abstract Background: The Follicular Lymphoma International Prognostic Index (FLIPI) has been developed to predict prognosis and to allow risk adapted treatment decisions in patients with follicular lymphoma (FL) before the widely use of Rituximab. However, the addition of Rituximab to standard induction chemotherapy with its long-term beneficial effects has profoundly changed the treatment outcome in patients with advanced stage FL and has become the new standard in the first line therapy of this disease. Therefore, we addressed the question, whether the prognostic value of the FLIPI could be reconfirmed in patients with advanced stage FL treated initially with a rituximab/chemotherapy combination. Methods: The FLIPI index was tested in patients treated with Rituximab and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone, R-CHOP) in a prospective multicenter phase 3 trial of the GLSG using the time to treatment failure (TTF) as target parameter. Results: 362 Patients treated with R-CHOP were evaluable for TTF. Of the 338 patients evaluable for all FLIPI risk factors, 14% of patients were classified as low, 41% as intermediate and 45% as high risk. After a median follow-up time of 20 months, patients with low risk and intermediate risk FLIPI had almost identical TTF (2-years TTF 92% vs 90%, 95% C.I., 83% to 100% and 84% to 96%, respectively). In contrast, the TTF was significantly shorter in the high risk FLIPI group (2-years TTF 67%, 95% C.I., 58% to 76%) as compared to the combined low/intermediate risk FLIPI group (relative risk 3.0, 95% C.I., 1.7 to 5.1; p &lt; 0.0001). In addition, responding patients with high risk FLIPI had a significantly shorter progression free survival as compared to the low/intermediate risk group (relative risk 3.3, 95% C.I., 1.8 to 6.0; p &lt; 0.0001). When postremission treatment was taken into account, the FLIPI separated the high risk group from the low/intermediate risk group in 65 patients treated with autologous stem cell transplantation (relative risk 6.0, 95% C.I., 1.4 to 25.2) as well as in 242 patients who had received IFN-α maintenance or no postremission therapy (relative risk 3.2, 95% C.I., 1.8 to 5.8). As the FLIPI was able to separate the high from the low/intermediate risk group in patients with advanced follicular lymphoma treated initially with Rituximab and CHOP we next performed a multivariate analysis to determine the impact of the individual parameters incorporated in the FLIPI on the TTF. The serum LDH level greater than the upper normal limit (relative risk 2.6, 95% C.I., 1.5 to 4.5) and the hemoglobin level below 12 g/dl (relative risk 2.5, 95% C.I., 1.4 to 4.3) were independently associated with a shorter TTF in these patients, whereas the age and the number of nodal areas were not discriminant. Conclusion: Taken together, these data indicate that the FLIPI is a valid prognostic index for identifying high-risk patients in FL, also after front-line combined immuno-chemotherapy. The index will remain an important tool to adjust treatment decisions in individual patients according their risk profile and to design clinical trials for the different risk groups in the era of antibody-based therapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xue Shi ◽  
Xiaoqian Liu ◽  
Xiaomei Li ◽  
Yahan Li ◽  
Dongyue Lu ◽  
...  

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had &gt;50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3100-3100
Author(s):  
Ayumi Numata ◽  
Katsumichi Fujimaki ◽  
Naoto Tomita ◽  
Masatsugu Tanaka ◽  
Chizuko Hashimoto ◽  
...  

Abstract Abstract 3100 The Follicular Lymphoma International Prognostic Index (FLIPI) is the most useful prognostic index for follicular lymphoma (FL). FLIPI was developed from retrospective data, which was based on treatment without rituximab (R) therapy and did not contain β2-microglobulin data of some cases. Recently the working group that had suggested FLIPI proposed FLIPI2, based on prospectively collected data. However, FLIPI2 contains data on several different treatment methods, such as treatment with or without R therapy. The present study aimed to retrospectively analyze the prognosis of FL uniformly treated with the combination of R, cyclophosphamide, doxorubicin, vincristin, and prednisone (R-CHOP). This study involved 114 patients consecutively diagnosed with FL who were treated with R-CHOP and were registered in the data-base of the Yokohama City University Hematology Group between January 2001 and October 2009. All the parameters required for FLIPI and FLIPI2 calculation were present in 108 patients (men, 53; women, 55, median age; 57 years [34- 78 years]). The median follow-up period was 31.7 months (0.8- 97.5 months). According to the FLIPI score, 50 patients (46.3%) were in the high-risk group (HR); 31 patients (28.7%), the intermediate-risk group (IR); and 27 patients (25.0%), the low-risk group (LR). On the basis of the FLIPI2 score, 45 patients (41.7%) were in HR; 52 patients (48.1%), IR; and 11 patients (10.2%), LR. According to FLIPI, the 5-year overall survival (5yOS) was 74.1% (95% CI, 58.1– 94.4%) for HR, 89.5% (95%, CI, 76.6– 100%) for IR, and 100% for LR (p = 0.0049); the 5-year time to failure (5yTTF) was 42.3% (95% CI, 26.0– 68.9%) for HR, 39.1% (95% CI, 22.7– 67.3%) for IR, 66.4% (95% CI, 47.2– 93.4%) for LR (p = 0.244). According to the FLIPI2 score, 5yOS was 71.3% (95% CI, 53.2– 95.6%) for HR, 85.6 % (95% CI, 72.0– 100%) for IR, and 100% for LR (p = 0.197), the 5yTTF was 35.8% (95% CI, 20.0– 64.2%) for HR, 46.7% (95% CI, 31.1– 70.3%) for IR, and 76.2% (95% CI, 52.1– 100%) for LR (p = 0.075). In conclusion, in FL patients treated with R-CHOP, FLIPI provided a more accurate OS than that provided by FLIPI2; however, FLIPI2 provided a more accurate TTF than that provided by FLIPI. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3057-3057
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Renata Oliveira Costa ◽  
Abrahão Elias Hallack Neto ◽  
Sheila Siqueira ◽  
Rodrigo Santucci ◽  
...  

Abstract Introduction: To evaluate a new enhanced IPI proposed by the National Comprehensive Cancer Network (NCCN-IPI) in DLBCL patients, we compared the international prognostic index (IPI), R-IPI and NCCN-IPI in DLBCL patients treated with rituximab, cyclophosphamide, hidroxydaunorubicin, vincristine and prednisone (R-CHOP). Methods: From June 2008 to November 2011 we retrospectively evaluated 146 DLBCL patients treated with R-CHOP-21 referred for cancer treatment in a single university institution in Brazil. Patient's clinical data were assessed to calculate the IPI, R-IPI and NCCN-IPI. Results: Patient's median age was 58.9 years (range 16 – 86); 85 (57.8%) were female. According to IPI, risk categories were low (n=41, 28.1%), low-intermediate (n=43, 29.5%), high-intermediate (n=37, 25.3%) and high (n=25, 17.1%). Using R-IPI, risk categories were very good (n=19, 13%), good (n=65, 44.5%) and poor (n=62, 42.5%). According to NCCN-IPI, risk categories were low (n=12, 8.2%), low-intermediate (n=52, 35.6%), high-intermediate (n=62, 42.5%) and high (n=20, 13.7%). At 30 months (median follow up 17.7 months - range 0.6-58.2 months) the overall survival (OS) was 75.5%. The progression-free survival (PFS) at a median follow-up of 16.3 months (range 0.6-52.4) was 68.3% for all patients. Using IPI, the OS at 30 months did not differ between low and low-intermediate risk patients (96.8% vs. 82.2%; p=0.136); however, it was higher than the OS of high-intermediate risk (n=37; 96.8% vs 74.1% p=0.11) and high-risk (n=25; 96.8% vs 41% p < 0.001) patients (Figure 1). The NCCN-IPI demonstrated significant differences in OS (p < 0,001) and PFS (p<0.001) among low-intermediate, high-intermediate, and high risk groups, with the high-risk group exhibiting worse OS (32.1% in 30 months) (Figure 2). According to IPI, the OS in high-risk patients was 41%. Figure 1: OS and PFS according to International Prognostic Index (IPI) Figure 1:. OS and PFS according to International Prognostic Index (IPI) Figure 2: OS and PFS according to NCCN-IPI Figure 2:. OS and PFS according to NCCN-IPI Figure 3 Figure 3. Conclusion: In our study the NCCN-IPI, but not the IPI or R-IPI was able to discriminate a high-risk group of DLBCL patients treated with R-CHOP with worse OS. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 33 (23) ◽  
pp. 2516-2522 ◽  
Author(s):  
Carla Casulo ◽  
Michelle Byrtek ◽  
Keith L. Dawson ◽  
Xiaolei Zhou ◽  
Charles M. Farber ◽  
...  

Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.


Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.


2021 ◽  
Author(s):  
Ádám Jóna ◽  
Anna Kenyeres ◽  
Sándor Barna ◽  
Árpád Illés ◽  
Zsófia Simon

Abstract Introduction: Follicular lymphoma (FL) is an indolent yet heterogeneous B-cell lymphoproliferative disorder. Most people respond to treatment well. However, a particular group of patients has a poor prognosis, and these patients are difficult to define.Patients and methods: We retrospectively analyzed FL patients treated at the University of Debrecen in the past 20 years. We investigated prognostic factors that may influence the survival of FL patients.Results: We found a standardized uptake value (SUV)max cut-off value of 9.85 at the staging PET/CT to significantly separate FL patients’ progression-free survival (PFS) (p=0.0003, HR: 0.2560, 95%CI: 0.1232-0.5318). Lymphocyte/ monocyte (Ly/Mo) ratio of 3.45 drawn at diagnosis also significantly predicted PFS (p=0.0324, HR: 1.806, 95% CI: 1.051-3.104). Combining patients’ with staging SUVmax >9.85 and Ly/Mo < 3.45 a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1033, 95%CI: 0.03719-0.2868). Similarly, a significant difference was shown with a SUVmax cut-off of 3.15 at the interim PET/CT (p<0.0001, HR: 0.1535, 95%CI: 0.06329-0.3720). Combining patients with staging SUVmax >9.85 and interim SUVmax >3.15, a high-risk group of FL patients can be identified (p<0.0001, HR: 0.1037, 95%CI: 0.03811-0.2824). The PFS difference is translated into overall survival advantage (p=0.0506, HR: 0.1187, 95%CI: 0.01401-1.005).Discussion: Biological prognostic factors, such as the Ly/ Mo ratio, may improve the prognostic assessment of staging PET/CT. Nevertheless, PFS difference is translated into OS when using a combination of staging and interim SUVmax. We consider investigating additional biological prognostic factors while currently highlighting PET/CT's role in FL.


2020 ◽  
Vol 4 (18) ◽  
pp. 4451-4462
Author(s):  
Stefan Alig ◽  
Vindi Jurinovic ◽  
Mohammad Shahrokh Esfahani ◽  
Sarah Haebe ◽  
Verena Passerini ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document