The adjuvant role of low dose total body irradiation following chemoimmunotherapy in elderly high risk patients with diffuse large B-cell lymphoma (DLBCL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17523-17523
Author(s):  
A. Safwat ◽  
L. Specht ◽  
F. Hansen ◽  
M. Hansen ◽  
A. Boesen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Risk ◽  
Total Body Irradiation ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Relative Increase ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Total Body

17523 Background: Results from the RICOVER-60 trial indicated a better outcome in elderly DLBCL patients (pts) by adding rituximab (R) to CHOP and shortening cycle intervals 14 days. We tested the addition of low dose total body irradiation (LTBI) to what proved to be the best performing arm of the RICOVER-60 trial (6xR-CHOP-14 + 2xR). Methods: A phase II trial including pts>60 yrs with stage II-IV, CD20-positive DLBCL was started in 2003 and is still ongoing. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Subpopulations of blood lymphocytes, monoctytes and dendritic cells were identified by multi-color flowcytometry during treatment. Results: 24 patients finished their treatment and were found to be predominantly high risk. Median age was 68 years; 50% had ≥ 1 extranodal lesion; 71% had stage III or IV; 63% had B symptoms; 58% had ECOG score ≥ 1; 75% had elevated LDH and 58% had IPI of >2. There were 3 toxic deaths (12.5%) due to sepsis occurring after 1st, 3rd and 5th chemotherapy cycle, respectively. One patient got off study because of disease progression. 14 pts achieved a CR or CRu at the end of chemotherapy, while 6 were in PR. After LTBI, all 6 PR pts converted to CR. 3 pts relapsed within 7 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. 94%, 100% and 98% of the administered R-CHOP-14, Rituximab and LTBI cycles respectively were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 22 of 135 R-CHOP-14 cycles (16%). CTC Gr. 3–4 thrombocytopenia was seen in 4 pts following the last LTBI cycle (16%). Preliminary data from multi-color flowcytometry of the first seven pts, showed depletion of circulating B-cells, but in some pts, a relative increase in the frequency of circulating dendritic cells during chemotherapy, which was enhanced by LTBI. Conclusion: In high-risk elderly DLBCL pts, R-CHOP-14 is associated with potential fatal infections. LTBI adds relatively little extra toxicities in the form of thrombocytopenia and may have the potential of converting PR patients to CR. Testing lymphocytic subpopulations in peripheral blood may help elucidating the immunomodulatory mechanisms of LTBI. No significant financial relationships to disclose.

Final Results of a Phase II Danish Trial Testing Low Dose Total Body Irradiation Following Six Bi-Weekly RCHOP-14 Plus 2 Extra Rituximab in Elderly High risk Patients with Aggressive CD20+ Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1013-1013
Author(s):  
Akmal Safwat ◽  
Lena Specht ◽  
Flemming Hansen ◽  
Mads Hansen ◽  
Jesper Jurlander ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Phase Ii ◽  
Total Body Irradiation ◽  
Low Dose ◽  
B Cell Lymphoma ◽  
Observation Time ◽  
Phase Iii ◽  
Total Body

Abstract Background: To further improve the results achieved by adding Rituximab (R) and shortening chemotherapy interval in elderly patients, an effective but relatively non-toxic treatment modality is needed. We tested therefore the addition of low dose total body irradiation (LTBI) of 1,6 Gy given after chemo-immunotherapy. Methods: A multicenter, phase II trial including patients >60 yrs with stage II-IV, CD20-positive DLBCL was performed between 2003 and 2007. Patients received 6x R-CHOP-14 + 2x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest. Radiotherapy to sites of bulky (>7.5 cm) disease was given according to the local guidelines of the participating centres. Results: Forty two patients were included. Observation time ranged from 3 to 47 months with median follow up of 24 months. The median age was 67 years; 62% had stage III or IV; 48% had B symptoms and 36% had bulky (> 7.5 cm) disease; 50% had ECOG score ≥ 1; 76% had elevated LDH and 57% had IPI of >2. Twenty four patients (57%) achieved a CR or CRu at the end of chemotherapy, while 12 (28.5%) were in PR. One of the 12 PR patients refused LTBI. Of the remaining 11 PR patients who received LTBI, 8 (82%) achieved CR in the first follow up after LTBI while the remaining 3 patients had initially stable disease but progressed shortly after. One patient (2%) progressed under chemotherapy while seven patients (17%) relapsed after achieving CR. Six of these refractory/relapsed cases presented with IPI ≥ 3. The 3-yr event-free and progression-free survival values were 64.8% (SE: 8.7%) and 73.5% (SE: 8.9%), respectively, while the 3-yr overall survival was 85.4% (SE: 5.5%). There were 3 toxic deaths (7.1%) due to sepsis occurring during chemotherapy. Ninteen of 235 cycles of CHOP (8%) were given at reduced dose levels in 3 patients (7%), while 3 cycles (1.3%) were delayed but given at 100% dose level. None of the 305 injections of Rituximab were dose reduced. Only one of 31 patients (3%) got his second LTBI cycle at 75% of the planned dose because of thrombocytopenia. CTC Gr 3–4 neutropenia occurred following 50 of 250 R-CHOP-14 cycles (20%). CTC Gr. 3–4 thrombocytopenia was seen in 8 pts (22%) following LTBI. Conclusions: Despite the high risk profile of the patient cohort enrolled in this trial, the 3-yr outcome values match the results of the best performing recent phase III clinical trials designed for elderly patients with DLBCL. Adding LTBI to 6 cycles of R-CHOP-14 was well tolerated and effective in converting the majority of PRs into CRs. Therefore, it may provide survival benefit and should be tested in a randomised setting.

scholarly journals Open-Labeled, Multicenter Phase II Study of Bortezomib for Maintenance Therapy in Patients with High Risk Diffuse Large B Cell Lymphoma (DLBCL): Borma Trial from Consortium for Improving Survival of Lymphoma (CISL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2884-2884
Author(s):  
Jae-Cheol Jo ◽  
Ho Sup Lee ◽  
Cheolwon Suh ◽  
Hye Jin Kang ◽  
Won Seog Kim ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
B Cell ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Risk Patients ◽  
Large B Cell Lymphoma ◽  
Risk Patients

Background: High-intermediate or high risk in international prognostic index (IPI) has a long-term chance of cure in the range about 50% in patients with diffuse large B cell lymphoma (DLBCL) treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib inhibits NF-κB activation through proteasome inhibition, providing rationale for its use in cells that constitutively express NF-κB. Non-germinal center B cell (GCB) DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic NF-κB pathway, which can inhibit chemotherapy. There is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed complete response (CR) after treated with R-CHOP. Methods: Patients with newly diagnosed stage II(bulky)-IV DLBCL with high or high intermediate IPI score of 3 to 5, and patients achieving a CR at the end of 6 or 8 cycles of R-CHOP21 were eligible for enrollment. Non-GCB DLBCL according to Hans criteria confirmed by central review was need before enrollment. Bortezomib maintenance treatment was consisted of bortezomib 1.3mg/m2 subcutaneously administration day 1 and day 15 per 28-day cycle with a total of 12 cycles. The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints were 3-year overall survival (OS), and toxicites. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: Fifty-nine patients were enrolled between May 2014 and Oct 2018. The type of Non-GCB DLBCL in all patients was confirmed by the central pathology review. The median age was 65 years (range: 27-86 years), and 60% were > 61 years. The baseline clinical features were as follows: female sex, 45.8%; ECOG >1, 10.2%; stage II bulky (>10cm), 6.8%; stage III/IV, 93.2%. At the time of analysis, 29 patients completed 12-cycles of bortezomib maintenance, and 3 patients is ongoing. Seven patients did not finished maintenance therapy due to toxicities (fatigue, atrial flutter, neuropathy, pleural effusion, thrombocytopenia), and withdrawal of informed consent (n=4). Sixteen patients experienced disease progression during bortezomib maintenance treatment. With a median follow-up of 25.1 months, 3-year PFS rate was 56.9% and 3-year OS rate was 86.4% (Figure 1). Toxicity was assessed in 489 cycles of bortezomib maintenance in all 59 patients. There was no treatment-related death and febrile neutropenia. Conclusion: Bortezomib maintenance showed 3-year PFS rate of 56.9% with acceptable toxicities in patients with high risk DLBCL achieving a CR at the end of 6 or 8 cycles of R-CHOP21. Figure 1 Disclosures Kim: Celltrion: Research Funding; Novartis: Research Funding; J + J: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

The Absolute Monocyte and Lymphocyte Counts at Diagnosis Predict Survival and Identify High-Risk Patients In Diffuse Large-B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3088-3088
Author(s):  
Ryan A. Wilcox ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
David James Inwards ◽  
Ivana Micallef ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Confidence Interval ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Good Risk

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

IPI In Selecting Patients With Diffuse Large B Cell Lymphoma in Rituximab Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5063-5063
Author(s):  
Sonja Genadieva-Stavrik ◽  
Alexandra Pivkova ◽  
Zlate Stojanoski ◽  
Borce Georgievski
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Abstract Nowadays, goal of treatment approach in diffuse large B cell lymphoma is cure and first step towards it is to achieve complete remission. DLBCL is a potentially curable disease, with curability highly dependent on clinical and biological features. According to the WHO classification of Hematological Malignancies, the entity of DLBCL is characterized by rapidly growing mature B cell tumors with large or relatively large cells and /includes a number of disease variants/entities / encompassing several distinct clinopathologic diseases, several different histologic variants and clinical subtypes. There is no unique treatment for all patients with diffuse large B cell lymphoma. Different subgroup of patients with DLBCL needs different treatment. In the pre-rutuximab era International Prognostic Index (IPI) was considered to be the most important prognostic factor for survival and the strongest indicator for identification of high-risk patients, who are unlikely to be cured with standard chemotherapy. Having in mind that IPI is based on 5 clinical characteristics (age, performance status, stage, extranodal involvement, LDH level) and it is constructed in the pre-rituximab is clear that R-IPI should be tested in rituximab era to provide any information of its validity. We retrospectively analyzed unselected population of 80 patients with confirmed diagnose of diffuse large B cell lymphoma treated at University hematology department in the period of 2005-2010. All patients were uniformly treated with R-CHOP regiment as initial treatment with curative intent. There were 80 patients with mean age 54, 5 years (15-84), male 35 and female 45. Older than 60 years were 29 patients (36, 25%). More than half of the patients (42) were diagnosed in advanced stage of the disease. We analyzed five prognostic factors: age, performance status, stage, extranodal involvement, LDH level and through the multifactorial analyses we selected two groups of patients. One with 0 to 2 factors as patients with low risk. Patients with more than 3 factors are considered as high risk. There is statistically significant difference in overall survival between two groups with five –years overall survival 70% for low risk patients and 47% for high risk. High-risk patients may be candidates for autologous transplantation as initial treatment, having in mind that in the rituximab era relapses occur very early in the first year and are difficult to be treated. R-IPI score is significant predictor and should be used for risk stratification of patients with aggressive B-cell lymphoma. However, these findings should be validated prospectively in an independent population of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Surgery on Long-Term Survival of Patients with Primary Gastric Diffuse Large B-Cell Lymphoma: A SEER Population-Based Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ju-Li Lin ◽  
Jian-Xian Lin ◽  
Ping Li ◽  
Jian-Wei Xie ◽  
Jia-bin Wang ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Intermediate Risk ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Background. The aim of this retrospective study was to compare the long-term survival of patients receiving conservative with surgical treatment to analyze the prognostic factors and the impact of surgery on oncological outcomes of patients with primary gastric diffuse large B-cell lymphoma. Methods. A total of 2647 patients diagnosed with primary gastric diffuse large B-cell lymphoma from 1998 to 2014 were extracted from SEER database. Propensity matching was performed to compare the clinicopathological characteristics of the two groups. Based on the recursive partitioning analysis, the patients were divided into three risk subgroups: low risk, intermediate risk, and high risk. Results. After propensity score matching, patient characteristics did not differ significantly between the two groups. The 5-year cancer-specific survival rates of the surgical group and the conservative treatment group were, respectively, 60% and 59.2% (P=0.952) before propensity matching and 64.2% and 58.6% (P=0.046) after propensity matching. According to the multivariate analysis, age, tumor stage, and chemotherapy and surgery were independent risk factors for long-term survival. The 5-year cancer-specific survival rates differed significantly between the low-risk, intermediate-risk, and high-risk patients (76.2% vs. 57.4% vs. 25.5%, respectively, P<0.001). The 5-year cancer-specific survival rate of the surgical group was significantly higher than that of the conservative treatment group in the low-risk patients. However, it did not differ significantly in the intermediate-risk and high-risk patients (P>0.05). Conclusions. A prognostic model was constructed based on the independent risk factors of age, tumor stage, and chemotherapy. The prognostic model indicated that low-risk patients (age<75 years, stage I/II, with/without chemotherapy) undergoing surgical treatment may benefit from long-term survival, while intermediate- and high-risk patients (age≥75 years, stage I/II, with/without chemotherapy or III/IV patients, with/without chemotherapy) gain no significant benefit from surgery.

scholarly journals Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma

Cancer ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 4283-4290 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Matthew Hellmann ◽  
Jeffrey A. Barnes ◽  
Peter Hammerman ◽  
Christiana Toomey ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell
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