Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma treated with R-CHOP.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19549-e19549
Author(s):  
Yan Qin ◽  
Haizhu Chen ◽  
Peng Liu ◽  
Changgong Zhang ◽  
Jianliang Yang ◽  
...  
Keyword(s):  
High Risk ◽  
Tp53 Mutation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Genetic Alterations ◽  
Prognostic Models ◽  
Intermediate Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19549 Background: Unlike BCL2 translocation ( BCL2TR), limited data about the prognostic significance of BCL2 mutations ( BCL2MUT) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2GA/AMP) and BCL2MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2TR. As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P< 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2GA/AMP. By contrast, neither BCL2MUT nor BCL2TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P< 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P< 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P< 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P< 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2GA/AMP, and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.

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

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

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

Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups

2012 ◽  
Vol 97 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Rika Kihara ◽  
Tomoyuki Watanabe ◽  
Takahiro Yano ◽  
Naokuni Uike ◽  
Seiichi Okamura ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Low Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals NCCN-IPI in Patients with Diffuse Large B CELL Lymphoma Treated with DA-R-EPOCH. Retrospective Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5401-5401
Author(s):  
Juan Miguel Bergua Burgues ◽  
Luis Lopez-Gomez ◽  
Fatima Ibañez ◽  
Sara Suarez-Varela ◽  
Julio Prieto-Fernandez ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Retrospective Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Large B Cell Lymphoma ◽  
Number Of Patients ◽  
Ann Arbor ◽  
Large B Cell

Abstract We analyzed the value of new NCCN-IPI index in patients affected of Large B cell lymphoma (LBCL) treated with DA-EPOCH-R in order to assess the validity of this index in patients treated homogenously with dose adjusted R-EPOCH. Patients and protocol: We analyzed the use of NCCN-IPI (Zhou et al, 2014) index in a retrospective cohort of 98 DLBCL patients treated with -EPOCH. These patients were included in DA-EPOCH using IPI(Shipp M.A., 1993) as criteria of inclusion, including only patients (95 patients, 96%)with suspected bad prognosis based in IPI (2-5) and 3 patients with primary mediastinal large B cell lymphoma (PMLBCL). R-EPOCH was administered as reported previously(Wilson et al, 2013). Only 10 patients (10%) were Ann Arbor stage I or II. Results: The median age of the cohort was 57,13(15-82), 47 woman, 75 patients alived. The median follow-up of the patients alive is 6,7 years (1,3-11). Ann Arbor stage was IVB in 44 patients, and IVA in 21. Responses during treatment: Complete response (CR): 81 (82%), refractory during treatment: 7 (7%), death during treatment: 7 (7%). The number of patients who relapsed after treatment was 19 (20%). The median overall (OS) survival of all patients was not reached, (at 5 years, 0.669, CI: 0.562-0.798). The progression free survival (PFS) at 5 years is 0.62, CI: 0.483-0.795. We classify by the new NCCN-IPI the patients in Low-Intermediate risk (L-I)(3 patients, 3%), High-Intermediate risk (H-I)(38, 44%) and High risk (HR) (45, 52%). The OS at 5 years in H-I is 0.839 (CI: 0.73-0.96) and HR was 0.56 (CI: 0.421-0.754), p=0.025. The PFS at 5 years in H-I is 0.65 (CI: 0.518-0.826) and HR is 0.57 (CI: 0.43-0.755), p=0.4. Conclusions: NCCN-IPI discriminates well prognosis between HR/H-I patients with DLBCNHL treated with DA-EPOCH-R. The results of this retrospective analysis of high and intermediate high-risk patients compares better than the published in patients treated with R-CHOP. PFS were similar in H-I and HR; differences in OS could be explain by differences in outcome after salvage treatment with autologous stem cell Disclosures No relevant conflicts of interest to declare.

Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4930-4935 ◽  
Author(s):  
Heidi Nyman ◽  
Magdalena Adde ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Minna Taskinen ◽  
Mattias Berglund ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Control Group ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractGerminal center (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL) and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. To determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome, GC and non-GC phenotypes were identified immunohistochemically from samples of 90 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)–like regimen (immunochemotherapy). One hundred and four patients previously treated with chemotherapy served as a control group. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed a significantly better overall (OS) and failure-free survival (FFS) than the non-GC group (OS, 70% vs 47%, P = .012; FFS, 59% vs 30%, P = .001). In contrast, immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy-treated patients (OS, 77% vs 76%, P = ns; FFS, 68% vs 63%, P = ns). In comparison, International Prognostic Index (IPI) could separate the high-risk patients from low- and intermediate-risk groups (OS, 84% vs 63%, P = .030; FFS, 79% vs 52%, P = .028). We conclude that rituximab in combination with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC- and non-GC phenotypes in DLBCL.

scholarly journals NCCN-IPI Is Superior to aaIPI and IPI in Predicting Survival of DLBCL in the Rituximab Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1872-1872 ◽  
Author(s):  
Yongqiang Wei ◽  
Yuankun Zhang ◽  
Xiaoxiao Hao ◽  
Xiaolei Wei ◽  
Weimin Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Chinese Patients ◽  
Intermediate Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Objective International prognostic index (IPI) has been widely used for predicting outcome in diffuse large B cell lymphoma. Although the introduction of rituximab to chemotherapy has dramatically improved the outcome of DLBCL, it also changed the prognostic value of IPI. The National Comprehensive Cancer Network IPI (NCCN-IPI) and age-adjusted IPI (aaIPI) were used to evaluate the prognosis for DLBCL in the rituximab era. However which one of them is more powerful in predicting survival remains unknown in Chinese patients. Patients and Methods A total of 334 patients with de novo diffuse large B-cell lymphoma diagnosed from 2003 to 2012 were included. All patients were treated with CHOP with or without rituximab. They were divided into CHOP and R-CHOP groups. IPI, NCCN-IPI and aaIPI score were recorded. Survival was performed according to the Kaplan-Meier (K-M) curves using the log-rank test. The predictive abilities of PI, NCCN-IPI and aaIPI were investigated by Harrell's C-statistics. Result Compared with the IPI, the NCCN-IPI and the aaIPI had better discrimination in different scores in all patients treated with or without rituximab. Both the NCCN-IPI and aaIPI had power in discriminating low, low-intermediate and high-intermediate risk groups. In comparison, the NCCN-IPI discriminated low-intermediate and high-intermediate risk groups (5-year overall survival [OS]: 74% vs 50%) better than the aaIPI (5-year OS: 80% vs 62%) in all patients and in the R-CHOP group with the NCCN-IPI 5-year OS: 85% vs 67% while the aaIPI: 87% vs 77%. In the CHOP group, the aaIPI discriminated low-intermediate and high-intermediate risk groups better (5-year OS: 70% vs 25%) than the NCCN-IPI (5-year OS: 60% vs 24%). According to the Harrel C statistic, the NCCN-IPI showed higher discrimination of the different scores (C_index: 0.669 ) than the aaIPI (C_index: 0.663 ) in all the patients (C_index: 0.669 vs. 0.663), especially in the R-CHOP group (C_index: 0.681 vs. 0.636). In the CHOP group, the aaIPI had stronger power (C_index: 0.711 ) than the NCCN-IPI (C_index: 0.683 ) in discriminating different scores. Conclusion The NCCN-IPI is more powerful than the IPI for predicting survival in the rituximab era. In patients aged 60 or younger and treated with CHOP without rituximab, aaIPI is a preferable tool for evaluating prognosis. Disclosures No relevant conflicts of interest to declare.

Novel Prognostic Model Of Primary Mediastinal Large B-Cell Lymphoma (PMBL): A Multicenter Cooperative Retrospective Study In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 638-638 ◽  
Author(s):  
Tomohiro Aoki ◽  
Koji Izutsu ◽  
Ritsuro Suzuki ◽  
Chiaki Nakaseko ◽  
Hiroshi Arima ◽  
...  
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
Pericardial Effusion ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background and Objective Primary mediastinal large B-cell lymphoma (PMBL) accounts for 2 to 4% of non-Hodgkin lymphomas and is characterized by distinct clinical, pathological and genetic features. Although the utility of DA-EPOCH-R without radiotherapy (RT) and a PET-guided RT approach were recently reported, a standard therapy has not yet been established, mostly due to the lack of data from prospective randomized studies. In addition, the prognosis for patients (pts) with relapsed PMBL is not well understood. Therefore, we conducted a multicenter, cooperative retrospective study to evaluate the clinical outcome of pts with PMBL. Patients and Methods We analyzed a total of 345 pts with newly diagnosed PMBL from 65 institutes between May 1986 and September 2012 in Japan. Pts were treated according to each institutional protocol or physicians' decisions. In pts treated with R-CHOP, the role of PET before RT was analyzed. In addition, we analyzed prognostic factors for PMBL pts and constructed a novel prognostic model using data from patients treated with R-CHOP. Results The median age was 32 (range, 17-83) years, and female pts were predominant (58%) among the patient population. Median tumor diameter was 10 cm. Stage I/II, low-risk by IPI, and PS 0/1 were also predominant (68%, 52% and 75%, respectively). The presence of pleural or pericardial effusion, elevated lactate dehydrogenase level and extra-nodal lesions were observed in 46%, 80% and 44% of pts, respectively. With a median follow-up of 48 months in surviving pts, overall survival (OS) and progression-free survival (PFS) at 4 years were 87% and 70%, respectively. The OS and PFS were improved in pts treated with rituximab(R)-containing chemotherapy (n = 267) (4-year OS: 91% vs. 77%, P < 0.001; 4-year PFS: 75% vs. 54%, P < 0.001, respectively). The OS at 4 years for patients treated with CHOP (n = 44), R-CHOP (n = 187), DA-EPOCH-R (n = 9), second- or third-generation regimens (n = 45; 28 with R and 17 without R), and chemotherapy followed by ASCT (n = 57; 43 with R and 14 without R) were 67%, 90%, 100%, 91% and 92%, respectively (P < 0.001). The PFS at 4 years were 40%, 71%, 100%, 83% and 76%, respectively (P < 0.001) (Figure 1). Consolidative RT was given to 42% of the patient population. A total of 119 of 187 pts treated with R-CHOP were assessed by PET/CT after the completion of R-CHOP, and 64 pts received consolidative RT after R-CHOP. In pts with negative PET after R-CHOP (n = 84), the OS (100% vs. 100%, P > 0.99) and PFS (92% vs. 72%, P = 0.36) at 4 years were similar when comparing pts treated with (n =25) or without RT (n =59). However, in pts with positive PET after R-CHOP (n = 28), both OS (100% vs. 60%, P = 0.010) and PFS (80% vs. 17%, P < 0.001) at 4 years were superior in pts who received RT (n = 21) than in pts who did not receive RT (n = 7). A total of 97 pts (28%) relapsed or progressed after first-line therapy. Of these, 67 (19%) and 11 pts (3%) relapsed in the mediastinum and CNS, respectively. Median time from initial diagnosis to relapse or progression was 9 months. Median OS after relapse or progression was 16 months and was higher in patients treated with stem-cell transplantation (SCT) (n = 58; 44 ASCT, 14 allogeneic SCT) than in patients who did not undergo SCT (4-year OS: 67% vs. 31%, P < 0.001). The IPI was predictive for OS (P = 0.002) and PFS (P < 0.001) in pts with PMBL treated with R-CHOP. Moreover, multivariate analysis showed that the presence of pleural or pericardial effusion was a significant and independent prognostic factor for PFS. We constructed a novel prognostic model (PMBL prognostic index; PMBIPI) and classified pts treated with R-CHOP into three different risk groups using these two factors (the presence of pleural or pericardial effusion, and IPI high/intermediate-risk or high-risk). For 93 pts (51%) classified as the low-risk group (0 factor), OS and PFS at 4 years were 97% and 89%, respectively. For 61 pts (34%) classified as the intermediate-risk group (1 factor), OS and PFS at 4 years were 85% and 59%, respectively. For 27 pts (15%) classified as the high-risk group (2 factors), OS and PFS at 4 years were 72% (P = 0.001) and 44% (P < 0.001), respectively (Figure 2). Conclusions The combination of R and chemotherapy improved outcomes for patients with PMBL. In addition, PET could predict the necessity for RT in pts with PMBL treated with R-CHOP. PMBIPI is a promising tool for risk-stratification of pts with PMBL. These findings require further validation in prospective studies. Disclosures: No relevant conflicts of interest to declare.

Retrospective Analysis of a New Prognostic Score for Diffuse Large B-Cell Lymphoma Based on Interim Positron Emission Tomography-Computed Tomography

2018 ◽  
Vol 139 (3) ◽  
pp. 148-157 ◽  
Author(s):  
TingBo Liu ◽  
LiHong Chen ◽  
Jie Pan ◽  
LiLi Pan ◽  
JianDa Hu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lymphoma ◽  
Prognostic Score ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Clinical Value ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: The International Prognostic Index (IPI) scoring system is the most widely used prognostic tool for diffuse large B-cell lymphoma (DLBCL); however, it fails to consistently identify patients with poor outcomes. This retrospective study was undertaken to confirm the clinical value of a new prognostic score and compare it with the IPI. Methods: The aim of this single-center study was to confirm the clinical value of a new prognostic score and its association with various clinical features, disease progression, and death in 70 patients with DLBCL who had undergone at least 6 cycles of chemotherapy. Results: The IPI and the new prognostic index were both associated with 3-year mortality (p ≤ 0.032); however, only the new prognostic index was associated with 3-year progression (p ≤ 0.036). Multivariate analysis showed that the new prognostic index was associated with 3-year progression but not overall survival. The new prognostic score also distinguished 3-year progression-free survival and overall survival in the low- and low-intermediate-risk groups as well as in the low-intermediate- and high-intermediate-risk groups. Conclusions: The new prognostic score represents a comprehensive prognostic model superior to the IPI. Prospective studies are necessary to explore whether treatment strategies may be adjusted using this new prognostic score.

The Sil Index Is a Useful Prognostic Indicator for Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1512-1512
Author(s):  
Naoto Tomita ◽  
Taisei Suzuki ◽  
Kazuho Miyashita ◽  
Wataru Yamamoto ◽  
Kenji Motohashi ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Prognostic Indicator ◽  
Large B Cell Lymphoma ◽  
Standard Risk ◽  
Large B Cell

Abstract Background: Rituximab (R) plus CHOP (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) and revised IPI were reported as prognostic indicators for DLBCL in 1993 and 2007, respectively. Although they are widely accepted, the performance status (PS) factor is sometimes ambiguous or subjective. Therefore, we developed a new prognostic index, the SIL, that includes only three objective prognostic factors: the clinical stage (S), a soluble interleukin-2 receptor level >2,500 U/mL (I), and an elevated lactate dehydrogenase level (L) (Cancer Sci. 2012). This study was conducted to confirm the value of the SIL index in a larger cohort and in each risk stratification of patients and to validate the SIL index in an independent patient cohort. Methods: Between 2003 and 2012, we registered and treated 781 consecutive patients with DLBCL, excluding those with mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, and primary effusion lymphoma. All the included patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Patients in whom the initial therapy dose was reduced by >20% were excluded. Finally, 572 of 781 patients were retrospectively analyzed. Patients with partial remission (PR) after the initial four cycles underwent eight R-CHOP cycles in total, whereas those who did not achieve PR after the initial four R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. If deemed necessary by the attending physician, additional local irradiation was performed in patients with PR or complete remission.Furthermore, we verified the value of the SIL index in an independent cohort of 89 DLBCL patients. Results: The median age at diagnosis was 63 years (range, 18-89 years). The median number of therapy cycles was 6 (range, 1-8), and 90% of patients received >6 cycles. Sixty-one patients (11%) received radiation therapy as primary treatment, which was often used to treat sites of residual masses at the end of chemotherapy. The median observation time for survivors was 55 months (range, 1-131 months). For 572 patients, the 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates were 70% and 81%, respectively. The 5-year PFS rate was significantly different as 86%, 73%, 63%, and 41% for 0, 1, 2, and 3 of SIL index, respectively (Fig 1; P < 0.0001). The 5-year OS rate was also significantly different as 92%, 87%, 78%, and 52% for 0, 1, 2, and 3 of SIL index, respectively (P < 0.0001). According to the SIL index, 367 (64%) and 205 patients (36%) were classified as having standard (SIL index: 0 or 1) and high (SIL index: 2 or 3) risks, respectively. In patients with a low/low-intermediate risk on the IPI, 84% were categorized as having standard risk according to the SIL index, whereas in patients with a high-intermediate/high risk on the IPI, 82% were categorized as having high risk according to the SIL index. Five-year PFS rates in the standard and high risk groups according to the SIL index were 79% and 53%, respectively (Fig 2; P < 0.0001). Five-year OS rates in the standard risk and high risk groups were 90% and 66%, respectively (P < 0.0001). Cox regression analysis of the SIL index, age (>60 years), PS (2-4), sites of extranodal involvement (>1), and sex showed that the SIL index (P <0.0001; hazard ratio [HR]: 2.38) and PS (P = 0.005; HR: 1.73) were independent risk factors for PFS. Similarly, the SIL index (P < 0.0001; HR: 2.62) and PS (P = 0.006; HR: 1.89) were independent risk factors for OS. When patients were divided into two groups by age (<60 years and >60 years), the SIL index was a good prognostic indicator for PFS and OS in both groups. When they were divided by the number of extranodal involvement sites (0-1 and >1), and sex, the SIL index was still a good prognostic indicator for PFS and OS in both groups. Lastly, when they were divided by the PS (0-1 and 2-4), the SIL index was effective in the good PS group. However, in the poor PS group, the SIL index showed a statistically significant difference in the OS, but not in the PFS. In the validation cohort analysis, 5-year PFS rates in the standard and high risk groups were 81% and 49%, respectively (Fig 3; P = 0.001). Five-year OS rates in the standard risk and high risk groups were 87% and 59%, respectively (P = 0.003). Conclusion: The SIL index is a simple and objective prognostic indicator for DLBCL patients treated with R-CHOP. Disclosures Fujita: Chugai Pharmaceutical CO.,LTD.: Honoraria.

scholarly journals Impact of Pegfilgrastim Approval on Relative Dose Intensity and Outcomes of R-CHOP for Diffuse Large B-Cell Lymphoma

2021 ◽  
Author(s):  
Yuka Morita ◽  
Yusuke Kanemasa ◽  
Yuki Sasaki ◽  
An Ohigashi ◽  
Taichi Tamura ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Relative Dose Intensity ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Maintaining the relative dose intensity (RDI) of chemotherapy with R-CHOP improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved for use in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI. We herein reviewed 334 patients with DLBCL who received six or more courses of R-CHOP and retrospectively analyzed the difference in the RDI, overall survival (OS), and progression-free survival (PFS) between patients whose treatment started after November 2014 (the post-approval group) and those whose treatment started before October 2014 (the pre-approval group). The incidence of FN was lower (39.2% vs. 62.2%, P < 0.001) and the RDI of R-CHOP was higher (86.8% vs. 67.8%, P < 0.001) in the post-approval group. The RDI of patients aged < 70 years was maintained at a high level even if their RDI was predicted to be low based on the model derived from the pre-approval group. Pegfilgrastim was administered to many of these patients and was thought to have contributed to the high RDI maintenance in the post-approval group. The 5-year OS (85.7% and 69.9%, P = 0.009) and PFS (81.4% and 64.4%, P = 0.011) were superior in the post-approval group. In this group, improved survival outcomes were observed among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs. 61.3%, P = 0.019) and high risk on the NCCN-IPI (5-year OS: 80.7% vs. 32.4%, P = 0.014). Maintenance of high RDI of R-CHOP and significant improvement in clinical outcomes, especially in high-risk groups, were observed after pegfilgrastim approval.

scholarly journals The Application of the ThroLy Risk Assessment Model to Predict Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 27 ◽  
pp. 107602962110459
Author(s):  
Hikmat Abdel-Razeq ◽  
Mohammad Ma’koseh ◽  
Asem Mansour ◽  
Rayan Bater ◽  
Rula Amarin ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Assessment Model ◽  
Risk Assessment Model ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background Patients with aggressive lymphomas are at higher risk for venous thromboembolism (VTE). ThroLy is a risk assessment model (RAM) derived to predict the occurrence of VTE in various types of lymphomas. In this study, we assess the clinical application of ThroLy RAM in a unified group of patients with diffuse large B-cell lymphoma (DLBCL). Methods Hospital databases were searched for patients with DLBCL and radiologically-confirmed VTE. Items in the ThroLy RAM, including prior VTE, reduced mobility, obesity, extranodal disease, mediastinal involvement, neutropenia and hemoglobin < 10.0 g/dL, were retrospectively reviewed. Results A total of 524 patients, median age 49 (range: 18-90) years were included. Patients had high disease burden; 57.3% with stage III/IV and 34.0% with bulky disease. All were treated on unified guidelines; 63 (12.0%) had primary refractory disease. Venous thromboembolic events were reported in 71 (13.5%) patients. Among 121 patients with high (> 3) ThroLy score, 22.3% developed VTE compared to 8.4% and 12.4% in those with low and intermediate risk scores, respectively ( P = .014). Simplifying the ThroLy model into two risk groups; high-risk (score ≥ 3) and low risk (score < 3) can still segregate patients; VTE developed in 44 (17.2%) high-risk patients ( n = 256) compared to 27 (10.1%) in the low-risk group ( n = 268), P = .038. Neutropenia, a component of the ThroLy, was encountered in only 14 (2.7%) patients. Conclusions ThroLy RAM can identify patients with DLBCL at high risk for VTE. Model can be modified by dividing patients into two, rather than three risk groups, and further simplified by omitting neutropenia.

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