High incidence of venous thromboembolic events (VTE) in patients with diffuse large b-cell lymphoma

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.

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The Application of the Lymphoma International Prognostic Index to Predict Venous Thromboembolic Events in Diffuse Large B-Cell Lymphoma Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.677776 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hikmat Abdel-Razeq ◽

Mohammad Ma’koseh ◽

Rashid Abdel-Razeq ◽

Rula Amarin ◽

Alaa Abufara ◽

...

Keyword(s):

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Thromboembolic Events ◽

Large B Cell Lymphoma ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Risk Patients ◽

Large B Cell

BackgroundVenous thromboembolic events (VTE) are commonly encountered in patients with lymphoma. Several risk assessments models (RAM) had attempted to identify higher risk patients with varying success. The International Prognostic Index (IPI) is a clinicopathological tool developed to help predict both response to treatment and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).ObjectiveIn this study, we utilize the IPI index to identify group of patients with DLBCL at higher risk for VTE.Patients/MethodsPatients with pathologically-confirmed diagnosis of DLBCL and with image-confirmed VTE, treated and followed at our institution were included. Rates of VTE was calculated for each risk category.ResultsA total of 373 patients, median age 49 (range: 18-90) years were included. VTE were reported in 56 (15.0%) patients; 51 (91.1%) had active disease while 29 (51.8%) were ambulatory at time of VTE diagnosis. VTE rates were particularly high among patients with poor performance status (26.2%, P=0.028) and high LDH (19.0%, P=0.023). Applying the age-adjusted IPI separated patients into two risk categories; VTE were diagnosed in 9.7% in patients with “low and low-intermediate” scores compared to 19.8% in patients with “high and high-intermediate” scores, P=0.020.ConclusionsThe original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.

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Faculty Opinions recommendation of High Incidence and Clinical Significance of MYC Rearrangements in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733826394.793559646 ◽

2019 ◽

Author(s):

Eduardo Calonje ◽

Jose Cardoso

Keyword(s):

B Cell ◽

Clinical Significance ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

High Incidence ◽

Large B Cell

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Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors

PLoS ONE ◽

10.1371/journal.pone.0224247 ◽

2019 ◽

Vol 14 (10) ◽

pp. e0224247 ◽

Cited By ~ 2

Author(s):

Hee Young Na ◽

Ji-Young Choe ◽

Sun Ah Shin ◽

Hyun-Jung Kim ◽

Jae Ho Han ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

High Incidence ◽

Large B Cell

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The Analysis of Prognostic Significance of Absolute Lymphocyte Count and Lymphocyte-to-Monocyte Ratio in Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.5379.5379 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5379-5379

Author(s):

Haiwen Huang ◽

Ying Liu ◽

Zhengming Jin ◽

Wu Depei

Keyword(s):

B Cell ◽

Lymphocyte Count ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Absolute Lymphocyte Count ◽

Lymphocyte To Monocyte Ratio ◽

Large B Cell Lymphoma ◽

High Incidence ◽

Ann Arbor ◽

Large B Cell

Abstract 【Objective】 To evaluate the prognostic value of absolute lymphocyte count (ALC)and lymphocyte-to-monocyte ratio (LMR) in Diffuse large B-cell lymphoma(DLBCL) when they are diagnosised. 【Methods】 Sixty-nine cases were analyzed retrospectively, including sex, age, stage, B symptoms, absolute lymphocyte count, absolute monocyte count, lymphocyte-to-monocyte ratio, lactate dehydrogenase, IPI score, bulky disease, ECOG performance status, number of extranodal involvement. Thirty-four received CHOP treatment (cyclophosphamide, vincristine, adriamycin, dexamethasone) , thirty-five received R-CHOP (rituximab plus CHOP). The ALC, AMC, LMR cutoff value for survival analysis were 1.0×109/L, 0.3×109/L, 2.6 respectively. All data were analyzed by statistical package for the social sciences (SPSS) software ‘‘version 18.’’ Chi-square test wasused to compare the difference between two groups of means. The Kaplan–Meier method was used to summarize OS and PFS and the logrank test was used for univariable analysis. The Cox proportional hazards model was used for multivariable analyses of measured factors. 【Results】 1. Patients with ALC<1.0×109/L had a high incidence of advanced Ann Arbor stage (P=0.003) , B symptoms (P=0.001) , elevated LDH level (P<0.001), high IPI score (P<0.001) and high ECOG score (P=0.001). Similar results were observed in patients with LMR<2.6. Patients with LMR<2.6 had a high incidence of advanced Ann Arbor stage (P<0.001) , B symptoms (P=0.005) , elevated LDH level (P<0.001), high IPI score (P<0.001) and high ECOG score (P=0.006). 2. In comparison with CHOP and RCHOP treatment, OS was significant longer with rituximab, as well as PFS(P＜0.05). 3. After a median 41.5 months follow-up, K-M analysis showed that lower ALC and LMR associated with inferior overall survival (OS) and progression free survival (PFS) (P＜0.001). In CHOP treatment group, patients with lower ALC and LMR seemed to have worse OS and PFS ( ALC: P=0.002 in OS,and P=0.005 in PFS; LMR: P=0.011 in OS, and P=0.027 in PFS). We got the same results in RCHOP set (ALC: P=0.001 in OS ; P=0.001 in PFS / LMR: P=0.001 in OS ; P=0.002 in PFS). 4. In multivariate analysis, only ALC were proven as an independent prognosis factor of survival(P<0.05). 【Conclusions】 the ALC and LMR at diagnosis were independent prognostic factors of both OS and PFS for patients with DLBCL. These data suggest that ALC can be used in combination with other prognostic features to better predict the outcome of DLBCL. Disclosures No relevant conflicts of interest to declare.

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