A NATIONAL RETROSPECTIVE ANALYSIS OF CLINICAL OUTCOMES FOLLOWING ALLOGENEIC TRANSPLANTATION FOR HIGH GRADE B‐CELL LYMPHOMA (HGBL)

Introduction: Patients with either primary refractory or relapsed/refractory High Grade B-Cell Lymphoma have a poor outcome with convention therapy as illustrated by the Scholar 1 Study (Crump et al.). High-Grade B-Cell Lymphoma with MYC and BCL-2and/or BCL-6 rearrangements, often referred to as Double Hit Lymphoma (DHL) also have a poor outcome with a published overall survival (OS) of 23.3% to 58% (Niitsu et al, Johnson et al). More recently novel therapies such as CAR-T therapy have shown the potential to improve outcomes in these patients (Schuster et al). These patients were considered for allogeneic transplantation from 2007 to 2017 and we performed a retrospective analysis of the outcomes, prior to the introduction of a CAR-T program. Methods: Consecutive patients transplanted for HGBL between 2007-2017 in the EBMT database were included. Data collected included age, sex, pathology subtype (HGBL (including subtypes), Transformed follicular lymphoma (tFL), DHL), disease status at SCT, conditioning (myeloablative vs reduced intensity), engraftment, day 100 outcome, development of graft versus host disease (GvHD), Non-relapse mortality (NRM), OS and eligibility for CAR-T therapy. Results: Fifty patients (29M, 21F) with a median age 47 at diagnosis and 50 at SCT were included. The subtypes included were HGBL (n=29), tFL (n=11) and DHL (n=10). Indications for SCT were: primary refractory (n=17), relapse <12 months after primary treatment (n=12), previous Autologous-SCT (n=10) and DHL (n=11). The median lines of therapy was 4 (range 1 to 6). Conditioning used was myeloablative (n= 23) or reduced intensity (n= 27 ). The day 100 mortality was 8% (progressive disease 4%, NRM 4%) with a OS of 56% and mortality due to progressive disease 22% and NRM 16%. 23 patients were eligible for a licensed CAR-T product. Disease subtype influenced outcome with an OS for primary refractory HGBL, relapsed HGBL, tFL and DHL respectively of 53%, 58%, 57% and 89%. Disease status at time of SCT significantly influenced outcome with a OS of 74% for patients in PET negative remission at time of SCT vs 36% for patients with PET positive disease. Conclusion: In this retrospective analysis patients with high risk HGBL had an overall survival of 56%. The most common cause of mortality was relapsed disease. Patients with PET negative remission at time of transplant have a good outcome with an OS of 74%. In our cohort patients with DHL have a particularly good outcome; it is likely some of these patients with a non-immunoglobulin gene associated MYC translocation could be managed more conservatively based on recent evidence (ASH Sehn). This analysis will provide a baseline outcome in the national transplant centre in a challenging disease cohort prior to the introduction of a CAR-T program. Keywords: allogeneic stem cell transplant (alloSCT); diffuse large B-cell lymphoma (DLBCL); high-grade B-cell lymphoma with or without rearrangement of MYC and BCL2 and/or BCL6.