R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1615-1615
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Maria Giuseppina Cabras ◽  
Luca Nassi ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Bulky Disease ◽  
Symptomatic Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcomes of Cardiac Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Taha Al-Juhaishi ◽  
Ghaith Abu Zeinah ◽  
Sadeer Al-Kindi
Keyword(s):  
B Cell ◽  
Survival Data ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
P Value ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction: Cardiac lymphomas are very rare with diffuse large B-cell lymphoma (DLBCL) considered to be the most common histology. These lymphomas can be either local "primary cardiac" disease, or part of dissemination by systemic lymphoma. There is limited data regarding outcomes of patients with this disease. We sought to evaluate the outcomes of cardiac DLBCL in both pre- and rituximab eras using a large retrospective database. Methods: The public Surveillance, Epidemiology and End Results (SEER) database was used to identify all patients diagnosed with DLBCL and heart as the primary disease site. Data cutoff in the database was in 2016. Patients with missing date of diagnosis or survival data were excluded. Patients were divided into two groups based on diagnosis year, with rituximab cohort included all DLBCLs diagnosed in 2006 and later (2006 was FDA approval year of rituximab in untreated DLBCL). Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 106 patients were included in the final analysis, baseline characteristics are summarized in table 1. Median age at diagnosis was 69.5 years with only about 10% of patients being 50 years or younger. Most patients were white 71 (67%), had local stage I/II disease 68 (64.2%), and belonged to the rituximab era group 71 (67%). Most patients had chemotherapy 82 (77.4%), while only 25 (23.6%) had surgery, and 16 (15.1%) had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months (0-292). Median OS was 16 months (95% CI, 0.55 -31) for the pre-rituximab group, and was 26 months (95% CI, 7.5 - 45) for the rituximab group which were not statistically different (p-value =0.340). Median lymphoma-specific survival (LCS) was 30 months (95% CI, 8.0 -52) for the pre-rituximab group, and was 36 months (95% CI, 16 - 158) for the rituximab group which were not statistically different (p-value =0.295). OS and LCS were also not different between the two era groups when stratified by chemotherapy (figure 1). On univariate analysis, Chemotherapy was associated with better OS [HR = 0.472, 95% CI (0.277-0.806); p-value = 0.006] but not LCS [HR = 0.690, 95% CI (0.341-1.396); p-value = 0.302]. Using a multivariate analysis model, both OS and LCS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy (table 2). Conclusion: Cardiac DLBCLs are rare and affecting mostly the elderly. No significant improvement in outcomes were noted in the current rituximab era. Age, disease stage, and having health insurance were associated with better outcomes. The role of chemotherapy needs further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.

Concomitant Radiochemotherapy In The Treatment Of Refractory Or Locally Relapsed Diffuse Large B-Cell Lymphoma: A Single Center Retrospective Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5114-5114
Author(s):  
Emmanuel Gyan ◽  
Alban Villate ◽  
Severine Lissandre ◽  
Lotfi Benboubker ◽  
Martine Delain ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hematological Toxicity ◽  
Severe Toxicity ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction Primary refractory Diffuse Large B-Cell Lymphoma (DLBCL) as well as relapse after salvage therapy displays a poor prognosis. Salvage radiation therapy alone does not provide sufficient disease control on locally chemoresistant DLBCL. Autologous stem cell transplantation (ASCT) provides the best progression-free survival when salvaged patients are transplanted in Complete Response (CR). The objective of this study was to assess the effectiveness of CCR in locally relapsed or refractory DLBCL, followed by ASCT in responding patients. Material and methods We report the outcome of consecutive patients with locally relapsed or refractory lymphoma for which a decision of CRC was taken in a single institution. Each patient has been assessed by CT or PET-scan. The CRC regimen consisted in 3 cycles of Rituximab (375 mg/m² day 1), CDDP (30 mg/m² 3 days 1-3) and VP16 (120 mg/m² days 1-3) at 21 days intervals, with concomitant radiotherapy delivered to the residual disease sites, administrated in 2 Gy fractions per day to a total dose of 30 Gy, starting on day 1 of the second cycle. Responding patients received ASCT with a BEAM conditioning at the end of the procedure. Extra-hematological toxicity was ranked according to the Common Terminology Criteria for Adverse Events. Tumor response was evaluated according to IWG 1999 at 1 month after the last cycle of CRC, three months after ASCT if performed and during a quarterly follow-up. Results We identified 13 patients with localized chemoresistant DLBCL from January 2002 to April 2011 including 12 primary refractory forms. The median age was 56 years (20-76), 12 of 13 patients had received at least two lines of chemotherapy before inclusion with anthracycline and cisplatin. 11 patients achieved a partial response (85%) and 4 of them (31%) a complete response after the CRC. 8 (61.5%) patients were transplanted 1 month after the last cycle of CRC. 7 patients have relapsed within 6 months after the end of treatment. After a median follow-up of 37 months (range 21-125) for the surviving patients, 7 patients are alive and free of disease. The overall survival is 54%, and all surviving patients had been transplanted. No severe toxicity was reported. Conclusion CRC should be considered as an option in the therapeutic arsenal in refractory or locally relapsed DLBCL, especially in patients eligible for ASCT. Further research on CRC is warranted. Disclosures: No relevant conflicts of interest to declare.

VEGFA and VEGFR2 Genetic Polymorphisms and Survival In Patients with Diffuse Large B Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 994-994
Author(s):  
Min Kyoung Kim ◽  
Cheolwon Suh ◽  
Hyun Sook Chi ◽  
Hee Soon Cho ◽  
Kyung Hee Lee ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Vegf Receptor ◽  
Curative Intent ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 994 Background: Angiogenesis and angiogenic factors are increased in most lymphomas and it has been associated with adverse outcome or more aggressive behavior of malignant lymphomas in previous studies. There is substantial inherited genetic variability within VEGF and one of its receptors, VEGF receptor 2 (VEGFR2), including multiple single nucleotide polymorphisms (SNPs). The level of VEGF expression has been found to vary depending on the presence of a genetic polymorphism. Moreover, VEGFR2 gene polymorphisms affect the binding efficacy of VEGF to VEGFR2. We therefore assessed the association between VEGFA and VEGFR2 polymorphisms and survival outcomes in patients with diffuse large B cell lymphoma (DLBCL). Patients and Methods: This study included 494 patients with de novo DLBCL treated at 5 hospitals throughout Korea from August 2001 through August 2009. Patients were included if they were (1) ethnic Koreans; (2) had blood samples taken at diagnosis; (3) had been treated with R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisolone) with curative intent; and (4) were available for follow-up at the treating institution. Genes and polymorphisms known to modulate angiogenesis were selected. Criteria included: (1) SNPs involved in the VEGF pathway; (2) potentially functional SNPs predicting alterations in protein function; (3) SNPs relevant to outcomes in other settings; (4) and SNPs with a minor allele frequency >5% in the study population. We selected a total of five genotypes, three in the VEGFA gene (rs699947, rs833061, and rs3025039) and two in the VEGFR2 gene (rs1870377 and rs2305948). Results: There was a trend towards greater proportions of patients > 60 years (P=0.078) patients with bulky disease (P=0.072) and patients who did not achieved complete response (P=0.068) among the VEGF2R rs1870377 TT type than the TA+AA genotype patients. Of the five polymorphisms, VEGF2R rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, the TT genotype had worse OS (P=0.002) and PFS (P=0.004) than the AA+TA genotype. Among patients with low IPI scores (0 to 2), those with the VEGFR2 rs1870377 AA+TA genotype had significantly better OS (P=0.035); a similar difference for this genotype was observed among patients with high IPI scores (3 to 5) (P=0.043). Patients in the moderate (P=0.031) and high (P=0.043) risk subgroups, according to revised IPI scores, with the VEGFR2 rs1870377 AA+TA genotype also had better outcomes than those with the TT genotype. Multivariate analysis showed that the rs1870377 genotype was an independent prognostic factor for OS (HR for TT vs AA+AT, 1.71; 95% CI, 1.21 to 2.43; P=0.002) and PFS (HR for TT vs AA+AT, 1.57; 1.13 to 2.17; P=0.007). Age > 60 years (P=0.0001 for OS; P=0.0001 for PFS), LDH level > normal (P=0.005 for OS; P=0.003 for PFS), extranodal disease > 1 (P=0.013 for OS; P=0.017 for PFS) and presence of B symptom (P=0.0001 for OS; P=0.0001 for PFS) were also independent prognostic factors for the survival of patients with DLBCL. Conclusion: The VEGFR2 rs1870377 polymorphism may affect survival in patients with DLBCL. These findings suggest that increased angiogenic activity may be related to tumor progression in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

scholarly journals A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I–II diffuse large B-cell lymphoma (KROG 17-02)

2019 ◽  
Vol 60 (5) ◽  
pp. 677-684
Author(s):  
Mi Joo Chung ◽  
Won Kyung Cho ◽  
Dongryul Oh ◽  
Keun-Yong Eom ◽  
Jin Hee Kim ◽  
...  
Keyword(s):  
B Cell ◽  
Treatment Outcomes ◽  
Tumor Size ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Chop Chemotherapy ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.

scholarly journals Prognostic Significance of Pretreatment Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Patients with Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Siqian Wang ◽  
Yongyong Ma ◽  
Lan Sun ◽  
Yifen Shi ◽  
Songfu Jiang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

It is generally believed that there is correlation between cancer prognosis and pretreatment PLR and NLR. However, there are limited data about their role in diffuse large B cell lymphoma (DLBCL). This study aims to determine the prognostic value of pretreatment PLR and NLR for patients who have DLBCL. The associations between clinical characteristics and NLR and PLR were evaluated among 182 DLBCL patients from January 2005 to June 2016. The optimal cutoff values for high PLR (⩾150) and NLR (⩾2.32) in prognosis prediction were determined. The effect of NLR and PLR on survival was evaluated through multivariate Cox regression analysis, univariate analysis, and log-rank test. According to the evaluation results, patients with high NLR and PLR had significantly shorter OS (P=0.026 and P=0.035) and PFS (P=0.024 and P=0.022) compared with those who have low PLR and NLR. On multivariate analyses, IPI>2, elevated LDH, and PLR⩾2.32 were prognostic factors for OS and PFS in DLBCL patients. Therefore, we demonstrated that high PLR and NLR predicted adverse prognostic factors in DLBCL patients.

Acquired Immunodeficiency and Malnutrition in Patients Treated with Bi-Weekly CHOP-Based Chemotherapy for Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2443-2443
Author(s):  
Dorte Tholstrup ◽  
Mads Hansen ◽  
Peter De Nully Brown ◽  
Jesper Jurlander
Keyword(s):  
T Cell ◽  
B Cell ◽  
Opportunistic Infections ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Preliminary Evaluation ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract During the recent years CHOP-14/CHOEP-14 in combination with the monoclonal anti-CD20 antibody Rituximab has become the standard choice of treatment for non-localized, poor risk Diffuse Large B-Cell Lymphoma. We, and others, have observed a relative high incidence of opportunistic infections not normally associated with the short neutropenic periods of CHOP-based treatment. We therefore introduced a prospective risk-assessment study in February 2005. The aim of the study is to assess the degree of malnutrition and immunodeficiency that may be associated with bi-weekly regimens. This is a preliminary evaluation of the first 27 patients included. Median age was 60 (31–80), 21 (78%) had CS III/IV disease, 14 (52%) extranodal involvement, 19 (70%) elevated LDH, 9 (33%) a Performance Score ≥2, i.e.13 (48%) presented with IPI 3–5 disease. Furthermore, 7 (26%) had bone marrow involvement, 8 (30%) bulky disease and 17 (63%) B-symptoms. All patients received 6 or 8 cycles of CHOP-14/CHOEP-14, and 15 patients received Rituximab at day 1 of each cycle. Patients were examined four times: 1) before 1st cycle, 2) 14 days after 4th cycle, 3) 14 days after last cycle (i.e. 6th or 8th), and 4) 3 months after treatment. Examination included blood tests, bodyweight and DEXA-scans. 20 patients (74%) had a significant weight loss during treatment. However, 3/4 had regained normal weight three months later. Consistently, DEXA-scans demonstrated a significant reduction in total lean body mass in 12 (44%) patients. P-protein, p-albumin, and selected trace elements were decreased in about 1/4 of patients during treatment. However, most patients had significant declines in T-cell levels during treatment, and interestingly about 1/4 presented with very low T-cell levels at diagnosis. Thus, total CD3-count was low in 7 (26%) patients at diagnosis, and reduced under treatment in 23 (85%). Both CD4- and CD8-count was low in 6 patients at diagnosis, while CD4 was reduced under treatment in 24 and CD8 in 16 patients. Likewise, a significant decrease of IgA, IgM, and IgG subclasses developed during treatment (Table 1). We conclude that patients treated with bi-weekly CHOP-chemotherapy may develop severely decreased levels of T-cells and severe hypogammaglobulinemia, which may be related to an increased incidence of opportunistic infections such as PCP or CMV reactivation.

Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status &gt;1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

The Immunohistochemical Pattern of Indoleamine 2,3-Dioxygenase in Tumor Tissue Indicates the Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2924-2924 ◽  
Author(s):  
Soranobu Ninomiya ◽  
Nobuhiro Kanemura ◽  
Hisashi Tsurumi ◽  
Takeshi Hara ◽  
Naoe Goto ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Poor Prognosis ◽  
Tumor Tissue ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Indoleamine 2,3 Dioxygenase ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2924 Poster Board II-900 Introduction : Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan along the kynurenine pathway. Pro-inflammatory cytokines, such as IFN-g, induce IDO during the inflammatory response in many human cell types. The induction of IDO is synergistic in the presence of TNF-a, IL-1 or IL-6, and might be mediated by a signaling pathway from NF-κB and/or MAPKs. Furthermore, some metabolites derived from tryptophan by IDO, such as L-kynurenine, block antigen-driven specific T-cell proliferation and induce T-cell death. Thus, IDO activity might play an important role in regulation of the immune response exerted by antigen presenting cells and also provide transformed cells with a potent tool to help escape from assault by the immune system. Indeed, we have previously reported that high serum L-kynurenine level is associated with poor prognosis of diffuse large B-cell lymphoma (DLBCL) (ASH 2008 abstract 2812). Here, we investigated the IDO expression of patients with DLBCL. Patients and methods : The study protocol comprised a prospective, consecutive entry design that was approved by our Institutional Review Board. We investigated 119 patients between December 2003 and June 2008 who were histologically diagnosed with DLBCL according to the WHO classification. We performed immunohistochemical (IHC) analysis for IDO expression by mouse anti-human IDO monoclonal antibody. Patients aged <70 y received 8 cycles of either R-CHOP or R-THP-COP therapy. Each regimen consisted of rituximab (R: 375 mg/m2), cyclophosphamide (CPA: 750 mg/m2), doxorubicin (DOX) or tetrahydropyranyl-adriamycin (THP; 50 mg/m2), vincristine (VCR; 1.4 mg/m2, maximal dose 2.0 mg), and prednisolone (PSL; 100 mg daily). The R-THP-COP regimen included THP, an anthracycline derivative of DOX. Patients aged ≥70 y received 6 cycles of R-CHOP or R-THP-COP therapy. The chemotherapy cycles were repeated at 14-day intervals in patients aged <70 y, and at 21-day intervals in patients aged ≥70 y. Patients with bulky disease received radiotherapy ranging from 30 to 40 Gy. Responses to treatment were categorized as defined by Cheson et al. Results : The median age was 65.2 year (range, 24 - 88 y) and the median follow-up was 22.9 month (range, 0.60 – 55.4 mo). The IDO expression patterns were classified into 3 categories; diffuse positive, focal positive and negative patterns. The diffuse positive IDO expression in tumor tissue was found in 38 cases (32%). The focal positive and negative expression of IDO was 16 cases (13.4%) and 65 cases (54.6%), respectively. The diffuse IDO positive cells were lymphoma cells and the focal IDO positive cells were dendritic cells (DC) confirmed by IHC analysis. The CR rates of patients with diffuse positive IDO expression, focal positive and negative were 55.3%, 62.5% and 83.1%, respectively (P<0.05). The 3-year overall survival rates for patients with diffuse positive, focal positive and negative were 49.8%, 66.3% and 81.4%, respectively (p=0.001). IDO expression was not significantly associated with the classification of germinal center (GC) type nor non-GC type. Discussion : A poor prognosis of patients with positive IDO expression might suggest that local immunity in tumor tissue is depressed by increasing L-kynurenine levels. Hence, IDO expression contributes to refractory to chemotherapy for DLBCL. Interestingly, expression pattern of IDO was significantly related with response to the treatment and prognosis of DLBCL. In conclusion, IDO activity might play an important role in DLBCL and the cells which express IDO are important for the response to treatment and prognosis of this malignancy. IDO, therefore, might be a candidate of therapeutic targets for DLBCL patients who are resistance to chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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