Interim Positron Emission Tomography-Computed Tomography (PET-CT) Is Predictive of Post-Therapy Outcome in High Grade Transformation of Low Grade Lymphoproliferative Disorders
Authors: Imlay-Gillespie Louise , Kliman David Simon , Wong Kelly , Arthur Christopher , Coyle Luke , Fay Keith , Kerridge Ian H. , Mackinlay Naomi , Mulligan Stephen , Stevenson William , Ward Christopher M , Greenwood Matthew 
Published: November 2019

Abstract
Background
PET-CT has become an essential tool in the management of Lymphoma. PET-CT is utilized in both the initial staging of lymphoma as well as assessing treatment-response.
High grade transformation of a low grade lymphoproliferative disorder (LPD) is associated with a poor prognosis. Patients (pts) are usually treated with standard of care for Diffuse Large B-Cell Lymphoma (DLBCL) with R-CHOP but generally have poorer outcomes and can experience relapse of either low or high grade disease.
To our knowledge, PET-CT has not been evaluated as a prognostic tool for the subgroup of transformed DLBCL.
Methods
A retrospective audit was performed of patients treated at Royal North Shore Hospital in Sydney, Australia between 2003-2012. Pts were included if they were treated with Rituximab for DLBCL during the study period and if this occurred on a background of low-grade LPD. Clinical data including LPD type, initial staging, treatment and outcomes were also collected. Treatments were stratified into standard R-CHOP-like versus more intensive regimens including Hyper-CVAD and dose-adjusted R-EPOCH. PET-CT reports were reviewed at staging, interim and post-therapy time points and outcomes stratified to complete metabolic response (CR), partial metabolic response (PR) and progressive disease (PD),based on the nuclear medicine physician's report.
Results
64 pts were identified in the study period with median follow up 4.4 yrs (range, 50d-11yrs)Male:female ratio was 1:1. Median age was 65 yrs (range 30-89). LPD diagnosis included Follicular Lymphoma (FL) (75%), Chronic Lymphocytic Leukemia (CLL) (6%) and others (19%) that included Mucosa Associated Lymphoid Tissue and Marginal Zone Lymphomas. 39 pts (61%) had PET-CT reports available for review. 45 pts (70%) were treated with R-CHOP with the remainder having more intensive regimes. 26% of pts received consolidation radiotherapy. 13 pts (20%) underwent autologous and 6 (9%) proceeded to an had an allogeneic transplant. 3 yr OS and EFS was 89% and 73% respectively.
Univariate analysis demonstrated both interim and post therapy PET-CT to be significant for both OS and EFS (p<0.01) with three groups identified; CR, PR and PD with 3 year OS for negative interim PET of 100%, 91% and 0% accordingly. CR on end of therapy CT was associated with improved OS (p<0.05) but not interim CT (p=0.967). On multivariate analysis interim PET-CT was the strongest independent predictor for EFS but not OS (p < 0.05).
Discussion
PET-CT is an invaluable tool in the management of LPD. This retrospective review demonstrates the utility of interim PET-CT in the prognostication of pts with transformed LPD. Larger prospective studies should be considered using PET-CT to more accurately stratify treatment for pts with transformed LPD.
Figure 1. Figure 1.

Disclosures
Imlay-Gillespie: Novartis: Honoraria. Arthur:Amgen: Honoraria; Amgen: Honoraria; BMS: Honoraria. Mackinlay:Sanofi Aventis: Research Funding; Roche: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.