Lymphoma with Features Intermediate Between DLBCL and Burkitt Lymphoma: Better Outcome with Intensive Chemotherapy Regimens
Authors: Crockett David G , Perry Anamarija M. , Armitage James O. , Weisenburger Dennis D , Bast Martin , Loberiza Fausto R. 
Published: October 2019

Abstract
Abstract 2710
Introduction Recent refinement in B-cell lymphoma classification by the WHO in 2008 has defined an entity that exists in the gray zone between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Varying in morphology, immunohistochemical, or genetic features, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (Intermediate DLBCL/BL) has been reported to have a poor clinical outcome. We aim to describe the clinical factors affecting outcomes and compare therapy response in a representative population.
Methods A retrospective search of the Nebraska Lymphoma Study Group Registry from 1983–2009 meeting the diagnostic criteria for Intermediate DLBCL/BL yielded clinical data at presentation, follow-up, and treatment information. Treatments were grouped as CHOP-like +/− Rituximab (R) vs. intensive regimens (e.g. CODOX-M +/− R, R-EPOCH). Diagnostic slides were re-reviewed to verify the diagnosis. Probabilities of progression-free survival (PFS) and overall survival (OS) were approximated using Kaplan-Meier method. Cox proportional regression analysis was used to evaluate the clinical variables associated with risk of treatment-failure and death.
Results Our cohort of 63 patients had a median age of 69 (19–93), male sex in 49%, a Karnofsky performance status of at least 80 at time of diagnosis in 73%, an elevated serum lactate dehydrogenase (LDH) in 62%, and stage IV disease in 46%. International Prognostic Index (IPI) scores were low in 38%, low-intermediate in 27%, high-intermediate in 24% and high in 11%. The probability of PFS at 5 and 10 years was 25% (95% CI 15–37%) and 10% (95% CI 4–21%) respectively, with a median time to treatment-failure of only 5.7 months. The 5 and 10 year probability of OS was 32% (95% CI 21–44%) and 20% (95% CI 10–32%) respectively, with a median survival of 10.4 months. Univariate regression analysis showed the following factors to be associated with an increased risk for treatment-failure: Ann Arbor stage IV disease (HR 2.49, 95% CI 1.33–4.68); elevated LDH (HR 1.85, 95% CI 1.02–3.37) and having at least 2 extra-nodal sites (HR 2.12, 95% CI 1.12–4.04). The following factors were associated with an increased risk of death: elevated LDH (HR 2.03, 95% CI 1.08–3.81), stage IV disease (HR 1.88, 95% CI 1.00–3.45), and having at least 2 extra-nodal sites (HR 2.26, 95% CI 1.15–4.40). The IPI scores of low-intermediate, high-intermediate, and high risk were associated with treatment-failure (HR 2.01, 95% CI 1.00–4.11; 4.62, 95% CI 2.11–10.14; 6.11, 95% CI 2.31–16.17) respectively, and death (HR 2.57, 95% CI 1.23–5.37; 3.13, 95% CI 1.41–6.94; 8.30, 95% CI 3.07–22.43) respectively. The median OS of patients who received CHOP/CHOP-like regimens +/− R was 8.7 months, whereas those who received a more intensive regimen +/− R was 45 months (p=0.38). The median PFS was 5.4 months for CHOP/CHOP-like regimens +/− R and 52.3 months for a more intensive regimen (p=0.08) (Fig.1).Figure 1.Progression free survival intensive versus CHOP/CHOP-like regimens +/− Rituximab, p=0.08Figure 1. Progression free survival intensive versus CHOP/CHOP-like regimens +/− Rituximab, p=0.08
Summary Our analysis confirmed poor clinical outcome with stage IV disease, elevated serum LDH, at least 2 extra-nodal sites at presentation, or worse IPI score. There was a better outcome with intensive chemotherapy regimens. This study underscores the importance of early identification and proper treatment choice.

Disclosures:
No relevant conflicts of interest to declare.