Pre-Transplant PET Status May Not Impact on Survival Following Reduced-Intensity Allogeneic Stem-Cell Transplant for Lymphoma. However, Post-Transplant Surveillance with PET May Be Important for Directing Immunotherapy.
Authors: Lambert Jonathan R , Bomanji Jamshed B , Cooper Nichola , Hart Daniel P , Peggs Karl , Thomson Kirsty , Ell Peter J , Mackinnon Stephen 
Published: October 2019

Abstract
18F-FDG PET (PET) imaging is now widely used in the management of patients with lymphoma, and has a recognised role in disease staging at diagnosis, determining response to treatment, and predicting response to autologous stem-cell transplantation (SCT). Reduced-intensity allogeneic SCT (RIT) has become an established therapy for patients with refractory or relapsed lymphoid malignancies, but the role of PET in RIT is unknown. We performed a prospective study to assess the role of PET in predicting outcome in RIT, and in directing intervention post-transplant. Sixty four patients with lymphoma were recruited from a single academic transplant centre. Transplant conditioning comprised fludarabine, melphalan and in-vivo alemtuzumab, and cyclosporine was given from day –1 to 3 months after RIT. PET and CT scans were performed pre-RIT and at 3, 6, 9, 15, 24 and 36-months post-RIT. In patients with chemotherapy-sensitive disease as assessed by CT scan, pre-transplant PET appearances did not influence the decision to proceed to transplant. Patients who progressed or relapsed (using clinical, CT or PET results), or who had mixed hematopoietic chimerism, received escalating dose donor lymphocyte infusions (DLI) in the absence of graft-versus-host disease. All 64 patients were at least 15 months (range 18–73 months) post RIT (25 follicular lymphoma, 16 Hodgkin lymphoma, 9 high-grade lymphoma, 9 mantle cell lymphoma, 5 other lymphomas), of whom 38 were PET-positive pre-transplant. With a median follow-up of 41 months, the pre-transplant PET status, (negative vs positive) had no effect on overall survival (65% vs 68%), diseasefree survival (32% vs 34%), relapse rate (56% vs 57%), and current DFS (55% vs 60%). Thirty four episodes of progression and relapse were observed in 29 patients: of these 15 (44%) were first detected by abnormal PET appearances in the presence of a normal or stable CT. No relapses were first apparent on CT and not on PET. DLI (either alone or in combination with chemotherapy or monoclonal antibody) were administered in 25 episodes of progression and relapse, and were directed by PET alone in 11 (44%). In 19 of the 25 episodes CR was achieved within 6 months of treatment. Additionally, 11 patients had PET negative residual masses on CT post-transplant. These patients were not given DLI and only 2 subsequently relapsed at the sites which were anatomically abnormal on the CT scan. Pre-transplant PET status did not influence survival or disease-free survival following allogeneic RIT. However post-transplant, PET detected progressive/recurrent lymphoma before the development of new abnormalities on CT, and thereby allowed earlier administration of immunotherapy, in 44% of episodes. The majority of patients with non-18F-FDG-avid residual abnormalities on CT post-transplant remained in durable remission, without receiving any treatment. Overall, PET changed the management in 18 out of 64 patients (28%). These findings would suggest that in contrast to autologous SCT, allogeneic transplantation using reduced intensity conditioning ± DLI may result in good outcomes for patients with chemotherapy-sensitive lymphoma, regardless of pretransplant PET appearances. Post-transplant surveillance by PET is useful for directing earlier use of immunotherapy for progressive/recurrent disease, and PET can also be used to characterise post-transplant metabolically inactive CT masses and allow appropriate withholding of DLI.