Incidence Rate of Thromboembolic Events (TE) In a Prospectively Evaluated Population of Patients with Lymphoma Enrolled In First Line Treatment Clinical Trials: a Report From the Gruppo Italiano Per Lo Studio Dei Linfomi (GISL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4208-4208
Author(s):  
Mauro Silingardi ◽  
Stefano Luminari ◽  
Elisa Barbolini ◽  
Fiorella Ilariucci ◽  
Dimitriy Arioli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Venous Catheter ◽  
Thromboembolic Events ◽  
Additional Risk

Abstract Abstract 4208 Introduction: Patients with lymphoma are considered at high risk of thrombosis, due to the disease itself or to the use of chemotherapy. The global risk of thrombosis is around 5%, higher in Non Hodgkin Lymphoma compared to Hodgkin Lymphoma and in advanced stages compared to localized disease. So far few studies have addressed the risk of thrombosis in lymphomas with a prospective approach. In 2007 we started a prospective study on patients with malignant lymphoma (ML) to assess the risk of thromboembolism in such patients and to identify possible risk factors. Methods: from March 1st 2007 all patients enrolled in any of the active clinical trials conducted by the Gruppo Italiano Studio Linfomi for the initial treatment of ML were screened for the occurrence of thromboembolic events (TE) at 3 timepoints: at the time of diagnosis (D), during chemotherapy (C) and during follow-up (F). For each registered TE additional data were required with respect to presence of additional risk factors (drugs, bed stay, comorbidities), concomitant use of anticoagulants, venous catheter implant. A detailed description of TE with treatment and outcome details was also required. Results: as of July 20th 2010, 643 patients have been registered in an active GISL clinical trial. Lymphoma subtype was Follicular Lymphoma (FL) in 70%, Indolent Non Follicular Lymphoma (INFL) in 10%, Hodgkin Lymphoma (HL) in 6%, Mantle Cell Lymphoma (MCL) in 6%, Diffuse Large B Cell Lymphoma (DLBCL) in 7%. Patients had a median age of 57 years (range 16 to 86), the male to female ratio was 1.16: Stage was advanced (III-IV) in 84%. Median follow-up was 18 months. Overall 27 TE have been reported, which corresponds to a proportion of 4.4%. Most events occurred during treatment or follow-up (15 and 6 at C and F timepoints, respectively), while TE proportion at D was low (0.9%). TE rate (×100 person-year) was 3.9 in MCL, followed by other lymphoma subtypes: HL 3.8, FL 2.6, DLBCL 2.4, and INFL 1.8. Interestingly, in MCL all the TE occurred at the C and F timepoints, and these patients were treated with an intense chemotherapy regimen (alternating R-hyperCVAD and HD ARA-C and mtx), while other lymphomas received conventional dose chemotherapy. Overall, the only parameter associated with TE development was PS>2 (RR 6.2, P=0.013), while the RR is 3.8 (P=0.188) if the 21 TE at C+F timepoints are considered. So far, detailed informations concerning TE were received for 20 patients. Of these, only 3 had comorbidities (1 case of diabetes mellitus, 1 case of cardiovascular disease and 1 case of prostatic adenocarcinoma receiving hormonotherapy) and no prior DVT or PE have been described. Two of the 5 cases of bedridden patients stayed in bed for more than 7 days before experiencing TE. Seventeen patients took no thrombogenic drugs as ongoing estroprogestinic therapy or hormonotherapy. Five patients had a venous catheter implant, which was removed only in 1 case due to thromboembolic occurrence. Overall we registered 7 cases of PE and 13 cases of DVT. When looking at the TE event description, 14 patients have been recorded as symptomatic and 4 were already treated with anticoagulants when the TE was diagnosed. The most frequent sites of TE were femoral vein or jugular vein (3 and 3 events, respectively), while the principal diagnostic tool employed for the TE diagnosis was Color Doppler ultrasound. Conclusions: To the best of our knowledge this is the study with the highest number of newly diagnosed patients with ML prospectively considered for the risk of TE. It shows a lower than expected rate of TE, probably because there is a representation of the different histotypes which doesn't replicate the real incidence: Follicular Lymphoma, a subtype with low risk of TE, is certainly over-represented. Our data suggest that therapy is the most important cause for TE. Further analyses on reported events may help to identify additional risk factors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcome of Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Finnish Nationwide Population-Based Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Ilja Kalashnikov ◽  
Nea Malila ◽  
Sirkku Jyrkkio ◽  
Sirpa Leppa
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Age At Diagnosis ◽  
Solid Cancer ◽  
Population Based Study ◽  
Large B Cell Lymphoma

Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) with typically indolent clinical course. Although NLPHL is associated with favorable prognosis, late relapses, and a tendency to undergo transformation to aggressive lymphoma is seen in a substantial proportion of cases. Population-based long-term data on outcomes is limited. Aims We aimed to assess outcomes of the patients diagnosed with NLPHL in Finland. Methods We retrieved NLPHL patients diagnosed between 1995-2016 from the Finnish Cancer Registry (FCR) with complete follow-up to end of 2018. The Registry has an excellent coverage and provides accurate population-based nationwide data for all histologically verified cancers in Finland. Gender and events such as histologically verified progression and transformation were obtained from the FCR. Date of death or emigration was verified from the Population Register and underlying cause of death (COD) from Statistics Finland. COD was categorized into three groups: lymphoma, solid cancer, or other cause. Patients were categorized into diagnostic calendar periods (1995-2002, 2003-2010, 2011-2016), gender, according to relapse, transformation, and patient status (alive, dead, emigrated) by end of 2018. Standard descriptive statistical analyses were performed. Progression free survival (PFS) and all-cause overall survival (OS) was estimated via Kaplan-Meier method. Analysis of risk factors for OS and transformation was performed using the Cox proportional hazard model. Risk factors included diagnostic calendar period, age at diagnosis as a continuous variable (year), gender, relapse, and transformation. Multivariate analysis was performed including only factors with a p value < 0.05 from the univariate model. Two-tailed p-values < 0.05 were considered statistically significant. All statistical analyses were performed using R, version 4.0.2. Results We retrieved 414 patients with newly diagnosed NLPHL. Majority of the patients were males (n=320; 77%). Median age was 47 years (range 5 - 87), females being significantly older than males at diagnosis (59 vs 44 years; p < 0.001). We did not observe any statistically significant differences in age at diagnosis, gender distribution, progression, or transformation rates between the calendar periods. Five- and 10-year OS for the entire patient cohort were 89% and 84%, and 5- and 10-year PFS 77% and 64%, respectively (Fig. 1, 2). Eighty-six (21%) patients had at least one histologically verified progression (range 1 - 4). During the 11.1 years (range 0.7 - 23.9) follow-up, 81 (20%) patients died. The underlying COD was any lymphoma in 34 (42%), solid cancer in 14 (17%) and other cause in 33 (41%) patients. Gender, age at diagnosis, and transformation were included in the multivariate model with respect to OS. Age at diagnosis (HR 1.07; 95% CI 1.05 - 1.09), and transformation (HR 2.6; 95% CI 1.5 - 4.7), but not gender, remained independent. We found histologically verified transformation to large B cell lymphoma in 25 (7.4%) patients with ≥ 5-year follow-up from NLHPL diagnosis. Transformation was the first event in 15 (60%) patients, and 10 (40%) patients had one or more NLPHL progressions prior to transformation. The median age at the time of transformation was 57 years (range 20 - 87) and 17 (68%) of patients were males. The transformation free proportion over 5 years of follow-up was 96% and 93% over 10 years (Fig. 3). In multivariate analysis, gender, and age at diagnosis were not significantly associated with the risk of transformation. The 5-year OS after transformation was 50% which was significantly lower compared to the nontransformed patients with 5-year OS of 90%. Fourteen (56%) of the transformed patients died during follow-up, 13 from lymphoma and 1 from other cause. Conclusion In this large nationwide population-based study, females were 15 years older than males at the time of diagnosis. Twenty-five patients (7.4%) developed transformation to large B cell lymphoma. Age and transformation were independent risk factors for poor survival, whereas progression of NLPHL and gender were not associated with adverse outcome. We did not observe any survival difference between diagnostic calendar periods. Lymphoma was the main cause of death. Figure Disclosures Malila: Cancer Society of Finland: Current Employment. Jyrkkio:Hospital District of Southwest Finland: Current Employment.

scholarly journals Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma Patients: Risk Factors and Outcomes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3611-3611
Author(s):  
Sabarish Ram Ayyappan ◽  
Vinita Gupta ◽  
Akiva Diamond ◽  
Brenda Cooper ◽  
Ben K. Tomlinson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
B Cell Lymphoma ◽  
Thromboembolic Events ◽  
Large B Cell Lymphoma ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Large B Cell

Abstract Venous thromboembolic events (VTE) are common after the diagnosis of lymphoma. Although various risk factors have been associated with VTE in cancer patients, there is no specific VTE risk prediction score for diffuse large B cell lymphoma (DLBCL) patients. The Khorana score is a prediction-model of VTE in cancer patients receiving chemotherapy that incorporates clinical and laboratory parameters. We evaluated the risk factors for VTE, the effect of VTE on the outcomes of DLBCL patients and the utility of the Khorana score in DLBCL patients. Methods: We searched the Hematologic Malignancies Database of University Hospitals Seidman Cancer Center for newly diagnosed DLBCL patients between 2002 and 2014. Data on patient characteristics including risk factors, disease characteristics, treatment, outcomes and VTE was collected. The Khorana score was calculated using clinical (disease type, body mass index) and laboratory (hemoglobin level, platelet and leukocyte count) parameters. Risk factors identified as having statistical significance on univariate Cox proportional hazards analysis (p <0.05) were selected for multivariate analysis. Cumulative incidence (with death as competing risk) was used to estimate the incidence of VTE. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan-Meier method; comparison between groups was done using the log-rank test. Results: Four hundred DLBCL patients were included for analysis. Median age at diagnosis was 63 with 235 patients above the age of 60. Two hundred and thirty seven patients (59.3 %) had advanced stage at diagnosis and 14 patients (3.5%) had a prior history of VTE. Baseline characteristics are listed in Table 1. Sixty percent of patients had a Khorana score of 1 with no risk factors in addition to the diagnosis of lymphoma. At median follow up of 33 months, 70 patients (18%) presented a VTE, with 1-year and 3-year cumulative incidence of 10.1% (95% CI 7.1-13.6) and 14% (95 % CI 10.8-18), respectively. Fifty-seven VTE (81% of all VTEs) were diagnosed in patients with active disease (at diagnosis, relapse or during active therapy). The Khorana score separated DLBCL patients in three VTE risk groups: intermediate (1 point), high (2 points) and very high (3 or more points) with 1 year cumulative incidence of VTE of 6.4%, 11.6% and 22.2%, respectively (p = 0.009) (Figure 1). On univariate analysis, bone involvement by lymphoma, elevated corrected calcium (>12g/dL), increased white cell count (>11,000/mcl), hemoglobin (<10g/dL), monocytosis (>800/mcl) and chromosomal translocations involving MYC presented statistically significant increases in hazard of VTE (Table 2). On multivariate analysis only bone involvement (p=0.017) and anemia (p=0.035) retained statistical significance as risk factors for VTE. Three-year OS for patients presenting with VTE within 1 year of DLBCL diagnosis was 46.7 % (95% CI 30-63.3) vs. 72.3% (95% CI 67.4-77.3) in subjects without early VTE (p=0.05) (Figure 2). Presence of VTE at any time after DLBCL diagnosis was also associated with worse OS rates, with estimated 3-year OS of 52.2 % (95 % CI 39.8-64.7) for subjects experiencing VTE and 74 % (95 % CI 69-79) for those without VTE after DLBCL diagnosis (p<0.0001). Conclusion: Venous thromboembolic events are common after diagnosis of DLBCL and are associated with worsened outcomes. The Khorana score is capable of identifying patient subgroups with increased risk of VTE. Additional parameters associated with aggressive disease and advanced stages could further help in VTE risk stratification for selection of patients who may benefit from antithrombotic prophylaxis. Prospective validation of VTE risk assessments and clinical trials of VTE prevention are needed in this high=risk population. Disclosures Caimi: Gilead: Consultancy; Novartis: Consultancy; Genentech: Speakers Bureau; Roche: Research Funding.

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.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

Primary Pancreatic Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4150-4150 ◽  
Author(s):  
Elisabeth S. Malin ◽  
Christiana E. Toomey ◽  
Jill Ono ◽  
Aliyah R. Sohani ◽  
James S. Michaelson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The Body ◽  
Advisory Committees ◽  
Not Otherwise Specified ◽  
Hodgkin's Lymphomas ◽  
Pancreatic Lymphoma

Abstract Abstract 4150 Introduction: Primary extranodal pancreatic non-Hodgkin lymphoma (PPL) makes up no more than 0.16–4.9% of pancreatic malignancies and less than 0.7% of non-Hodgkin's lymphomas (NHL). Since lymphomas involving the pancreas may have a similar clinical presentation to primary pancreatic adenocarcinoma, and often have a similar radiographic appearance, pancreatic lymphoma is often not diagnosed until surgical exploration or definitive surgery for presumed pancreatic cancer. Preoperative distinction of adenocarcinoma and PPL is critical as the management and prognoses of these malignancies are mutually exclusive. The rarity of PPL has made epidemiologic studies difficult to conduct. Methods: We queried our IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, for all adult patients diagnosed with PPL between 2000 and 2010. The database contains 5821 patients with mature lymphoid malignancies. Cases were included in the analysis if they met clinicopathologic criteria for PPL, defined as dominant disease presentation within the body of the pancreas. Forty-five patients were found to have pancreatic involvement at initial presentation of whom 31 (68.9%) on further investigation had a pancreatic primary and are included in the analysis. For each patient, we collected complete demographic information, clinical presenting features, histology, chemotherapy regimens, use of radiotherapy, and type of surgical biopsy performed. We also collected outcome data including results of interim and final restaging scans. Results: PPL represented 0.5% of all mature lymphomas seen at our institution. The median age at diagnosis was 60 yrs (range 20–91). There were 21 male and 10 female patients. Eighteen patients had Diffuse Large B Cell Lymphoma (DLBCL) (one with a focus of follicular lymphoma (FL) grade 3), two each had Burkitts Lymphoma, FL Grade 1–2, and mantle cell lymphoma (MCL), and one each had small lymphocytic lymphoma (SLL), Hodgkin Lymphoma, Marginal zone lymphoma, and peripheral T cell Lymphoma not otherwise specified. Three patients had NHL not otherwise specified (NOS). Of the 31 patients, 13 patients were stage 4E, 5 were stage 3E, 8 were stage 2E, and 5 were Stage 1E. Seventeen patients presented with jaundice. In 2 cases clinical history at presentation was unavailable. Elevated lactate dehydrogenase (LDH) level was present in 18 of 26 patients (69%) for whom laboratory values were available. B symptoms were present at diagnosis in 13 patients, absent in 17 patients, and unavailable in 1. Diagnosis was made in sixteen patients by fine needle aspiration (FNA), in nine patients by core needle biopsy, in two by incisional biopsies, and four patients were diagnosed after a definitive pancreaticoduodenectomy (Whipple procedure). Information on therapeutic regimen was available for 24 patients. One of these 24 patients was treated with primary radiotherapy without chemotherapy for a grade 1–2 primary pancreatic FL. Twenty-three patients had initial chemotherapy: 8 with R-CHOP, 5 with CHOP, 2 with CVP, and 1 each with CHOP-14, CVP × 1 then CHOP, R-CVP, R-EPOCH, R-CODOX-M/R-IVAC, R-CDOP and R-CP then R-CHOP. One patient was treated with chemotherapy not otherwise specified in the medical record. Four of these 23 patients received consolidative radiotherapy after initial therapy. Chemotherapy had significant efficacy with an overall response rate (ORR) of 75% in all chemotherapy treated patients (10 CR, 8 PR). Therapy information was available on 13 patients with DLBCL with an ORR of 85% (7 CR, 4 PR) to R-CHOP in 8 patients, CHOP in 3, and 1 each R-EPOCH and R-CDOP. One patient died of meningeal relapse of DLBCL despite therapy with R-EPOCH. For the entire PPL group at median follow-up of 28.5 months, the progression free and overall survivals are 48.4% and 64.5%, respectively. At a median follow-up of 33.4 months, the progression free and overall survivals for the DLBCL-PPL group are 50.0% and 66.7%, respectively. Discussion: PPL is a rare extranodal presentation of lymphoma accounting for 0.5% of lymphomas seen at a tertiary referral center. Pre-surgical diagnosis of PPL is critical to avoidance of unnecessary major surgery. The outcome of PPL approximates the outcome of DLBCL in other sites. An increased rate of CNS relapse was not seen with presentations in this extranodal site. Disclosures: Hochberg: Biogen Idec: Speakers Bureau; Genentech: Speakers Bureau; Enzon Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; WorldCare: Membership on an entity's Board of Directors or advisory committees; Proventys: Consultancy.

High Rate of Initial Treatment Failure in Patients with Primary Mediastinal B-Cell Lymphoma Treated with R-CHOP

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1601-1601 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Matthew D Hellmann ◽  
Yang Feng ◽  
Jeffrey A. Barnes ◽  
Tak Takvorian ◽  
...  
Keyword(s):  
Risk Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
Large B Cell Lymphoma ◽  
Ann Arbor ◽  
Large B Cell

Abstract Abstract 1601 Introduction: Primary Mediastinal B-cell Lymphoma (PMBCL) is an uncommon variant of Diffuse Large B-cell Lymphoma (DLBCL). Given the rarity of this disease, data guiding management is extrapolated from DLBCL trials, or from small retrospective analyses limited to PMBCL. Prospective evaluation of R-CHOP in the MiNT trial showed excellent results in PMBCL, but this trial was limited to young low risk patients. We present the largest retrospective series to date of R-CHOP for PMBCL in all risk groups. Methods: We identified cases of PMBCL at our institution using a comprehensive clinicopathologic database derived from tumor registry data. Natural language processing software was used to search pathology reports for terms of “mediastinal lymphoma,” “mediastinal large cell lymphoma,” “mediastinal large B-cell lymphoma,” as well as “lymphoma” in mediastinal biopsy specimens. Cases were included if they met clinicopathologic criteria for PMBCL, defined as a large B-cell lymphoma with typical features for PMBCL presenting with a dominant anterior mediastinal mass. All patients had to have been treated with R-CHOP. Progression-free survival (PFS) and overall survival (OS) are calculated by the Kaplan-Meier method and univariate analysis is performed to assess predictors of outcome. Results: Fifty-eight cases from 2000–2011 met inclusion criteria and are included in the analysis. The median age was 38 years (range 20–82) and 60% were male. Forty-four patients (76%) presented at limited Ann Arbor stage and 12 patients (21%) at advanced stage; presenting stage could not be discerned in 2 patients. Fifty-five percent of patients presented with mediastinal bulk ≥10cm in size; median size was 11cm (range 5–17cm). LDH was elevated at diagnosis in 60% of patients, normal in 21%, and unknown in 19%. By revised IPI score, 19% were low-risk (0 risk factors), 60% were intermediate risk (1–2 risk factors) and 12% were high-risk (≥3 risk factors). R-CHOP was given for a median of 6 cycles (range 1–8); 51 of 58 patients received 6 or 8 cycles. Among patients who achieved initial remission, 78% underwent consolidative radiotherapy and the remainder were observed after chemotherapy alone. The overall response rate was 81% (90%CI [71%–89%]) with 72% complete responses and 9% partial responses. Ten patients (17%) had primary refractory disease defined as progression on treatment or within 3 months of completion of therapy. Among 46 patients who achieved a response, 5 (11%) subsequently relapsed. Two patients, both elderly, died during treatment. Among the 10 patients with primary refractory disease, 6 have died from progressive lymphoma, 2 patients are alive with active disease undergoing salvage therapy, 1 is alive and free of disease greater than 8 years from diagnosis, and 1 was lost to follow-up. Among 5 patients with relapsed disease, 2 are alive without disease at last follow-up, while 3 have died of progressive lymphoma. Median follow-up for the entire series is 58 months. Five-year PFS is 68% (95% CI, 55% to 80%) and 5-year OS is 76% (95% CI, 65% to 88%). On univariate analysis, advanced Ann Arbor stage and high R-IPI score were associated with inferior PFS and OS. (p=0.006 and p<0.001, respectively for PFS, p=0.005 and p<0.001 for OS, log-rank test). Conclusion: PMBCL treated with R-CHOP carries an overall favorable prognosis, though primary refractory disease occurs in a significant number of patients, and is rarely curable with second line therapy. Advanced stage disease and high R-IPI scores are associated with inferior outcome. Novel treatment approaches warrant evaluation in high-risk patients. Disclosures: No relevant conflicts of interest to declare.

Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4260-4260 ◽  
Author(s):  
David Wrench ◽  
Hasan Rizvi ◽  
Andrew Wilson ◽  
Ciaran O'Riain ◽  
Andrew Clear ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Negative Impact ◽  
Tissue Sample ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separate tissue samples; n=21) lymphoma. The majority (n=18, 75%) of composite DLBCL/FL were diagnosed on lymph node (LN) sampling with the remainder identified in tonsil (n=3) with single cases in testis, salivary gland and BM. Discordant DLBCL/FL, presented as DLBCL and FL involving LN and BM respectively in 16 cases (76%). Other combinations included DLBCL and FL in separate LNs (n=2) and one each of kidney + BM, mesentery + LN, bone biopsy + BM. At presentation, DLBCL/FL had more advanced stage (p<0.01), higher IPI (p=0.02) and lower Hb (p=0.02) than dnDLBCL in keeping with BM involvement rates of 19/45 (42%) and 32/747 (4%), respectively. Most DLBCL/FL (n=42; 93%) received anthracycline based combination chemotherapy (a single case received HD-MTX and 2 cases palliative / no treatment both of whom died within 3.5 months) and, since 2003, addition of rituximab (24% of cases) to CHOP (n=10) or CODOX-M/IVAC (n=1); with similar rates of anthracycline (82%) and rituximab (29%) use in dnDLBCL. The 44 documented responses in DLCBL/FL included complete response (CR, n=26; 59% similar to 66% in 696 patients with dnDLBCL and assessable responses), partial response (n=7) and stable disease/progression (n=11) with a shorter RD for DLBCL/FL (median 8.7 yrs) compared to dnDLBCL (median not reached), although this was not statistically different (p=0.09). PFS was significantly shorter for DLBCL/FL in comparison with dnDLBCL (2.0 versus 4.6 yrs, respectively; p=0.02) and DLBCL/FL not achieving CR had inferior OS (0.4 yrs) than those achieving CR (11.5 yrs; p<0.01). Relapse after CR occurred in 12/26 (46%) patients with DLBCL/FL and in 142/456 (31%; p=0.13) of those with dnDLBCL; 83% and 87% relapsed cases have died, respectively. With a median follow-up of 10 yrs, 71% patients with DLBCL/FL have died as compared to 65% patients with dnDLBCL, and no differences in median OS were observed (4.0 yrs for DLCBL/FL versus 5.5 yrs for dnDLBCL; p=0.28). Death was most commonly due to lymphoma, the rate being similar in patients with DLBCL/FL (56%) and dnDLBCL (52%). However, LSS was shorter for DLBCL/FL (6.3 yrs) than dnDLBCL (13.8 yrs; p<0.01) and, with the long follow-up, we found no differences in OS between DLBCL with concordant (DLBCL, n=32) or discordant (FL, n=18) BM involvement (p=0.38). This study, to the authors’ knowledge the largest series of concurrent FL and DLBCL, confirms the relative frequency of DLBCL/FL to DLBCL (45:747, 6%) and demonstrates that the simultaneous presence of FL negatively influences the outcome of patients with DLBCL, by shortening PFS and LSS. This data emphasizes the importance of thorough staging at diagnosis, including BM biopsies, and highlights the need for better management of this population, which has a worse prognosis than dnDLBCL and is frequently excluded from clinical trials. Disclosures: No relevant conflicts of interest to declare.

Impact of absolute lymphocyte count on prognosis of aggressive non-Hodgkin lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19034-e19034
Author(s):  
Anahat Kaur ◽  
Punita Grover ◽  
Sheetal Bulchandani ◽  
Thomas A Odeny ◽  
Sheshadri Madhusudhana ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Absolute Lymphocyte Count ◽  
Intermediate Risk ◽  
Non Hodgkin Lymphoma

e19034 Background: Multiple studies have attempted to identify parameters to predict prognosis and overall survival (OS) in Non-Hodgkin Lymphoma (NHL). Revised International Prognostic Index (R-IPI) is commonly used but does not capture all predictive risk factors in the Rituximab era. Low absolute lymphocyte count (ALC) on follow up after first line therapy has been reported to predict relapse. The prognostic value and exact cut off for low ALC at diagnosis is not known. We aimed to investigate whether ALC at time of diagnosis is an independent predictor for OS in aggressive NHL. Methods: We retrospectively evaluated patients with aggressive NHL treated at our center from 1/2000 to 12/2016 with at least 2 year longitudinal follow up after diagnosis. We retrieved data for baseline characteristics including age, sex, Ann Arbor stage, R-IPI score, HIV status, histopathological diagnosis (Diffuse Large B Cell Lymphoma (DLBCL), Burkitt′s lymphoma, Follicular Lymphoma Grade IIIB, high-grade B cell lymphoma), type of chemotherapy and clinical response. Patients were divided into four subgroups based on ALC at diagnosis: < 500, 501-1000, 1001-1500 and > 1500X109/L. Statistical analysis was done using REDCAP and Stata v13. Results: A total of 92 patients were identified. The average age at diagnosis was 53.4 years, 63% were male and 73.5% were diagnosed with DLBCL. Per R-IPI score, 16.3% were high risk, 31.3% were high intermediate risk, 22.5% low intermediate risk and 30% were low risk. The median OS for patients with ALC < 500 x109/L (5.4%) was 1.5 years, ALC 501-1000 (38%) was 2.3 years, ALC 1001-1500 (23.9%) was 4.25 years and ALC > 1500 (32.6%) was 5.2 years. On multivariate analysis this difference was not statistically significant due to small sample size. Conclusions: We found that low ALC at diagnosis trended towards worse OS in aggressive NHL but did not reach statistical significance on multivariate analysis. Our study is limited by retrospective nature and sample size. Multicenter studies need to be done to validate these results. Studies are also needed to know the exact cut off for low ALC. [Table: see text]

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