The Use of PET Scans To Direct Immunotherapy Following Reduced Intensity Stem Cell Transplants in Adults with Lymphoid Malignancies.
Authors: Cooper Nichola , Avivi Irit , Karl Peggs S. , Hart Dan Q. , Thomson Kirsty , Bloor Adrian J.C. , Goldstone Anthony H. , Linch David C. , Ell Peter , Bomanji J. , Mackinnon Stephen 
Published: April 2020

Abstract
FDG PET scanning is increasingly being used to establish poor response and early relapse in patients with lymphoid malignancies in order to direct early intensification of treatment. We have performed a prospective study to assess the role of PET scans in directing immune manipulation (withdrawal of immune suppression and donor lymphocyte infusions (DLI)) following reduced intensity transplants (RIT) in patients with lymphoid malignancies. 34 patients (8 Hodgkin’s lymphoma, 3 Mantle cell lymphoma, 23 Non-Hodgkin’s Lymphoma), median age 44 years (range 20 to 64 years) have been entered since May 2002 and have &gt; 3months follow up. PET and CT scans were performed pre-RIT and at 3, 6, 9, 15 and 24 months post RIT. Patients were conditioned with fludarabine (30mg/m2x5) and melphalan (140mg/m2x1) and in vivo alemtuzumab. Cyclosporin (CSA) was given day −1 to 3 months after RIT. Progression was defined as persistent and/or increasing PET positivity. Relapse was defined as either new PET positive imaging (PET+), progression on CT scan (CT+) or clinical progression. DLI was subsequently given to patients who progressed or relapsed at escalating doses of 1 x 106/kg T cells up to 1 x 108/kg. Patients with active GVHD were excluded from DLI.
Results: 17 patients had positive PETs pre-treatment. 9 of these became PET negative, showing an anti-lymphoma effect of the conditioning regime. There were 7 TRMs, leaving 27 of 34 patients evaluable to assess the role of PET in post-transplant management. Of these 27 patients, 6 have had positive CT scans (CT+) with negative PET scans (PET-), with no evidence of clinical relapse. 10/27 patients have subsequently progressed on PET scan (PET+): 2 with PET+ and CT+ disease were not eligible for DLI (GVHD). Both progressed and died at 9 months. One patient is too early to evaluate. The remaining 7 patients received immunotherapy: 4/7 had CT negative (−) disease at PET+ relapse. One patient responded to CSA withdrawal, 6 responded to escalating DLI +/− rituximab (n=3): 3/7 having never developed CT+ disease. 2 patients have subsequently relapsed at 18 and 30 months and are being re-treated. In summary, negative PET scans prevented 6 patients from either undergoing invasive investigations or receiving potentially harmful DLI because of persistently abnormal CT scans. PET scans became positive before CT scans in 4 of 7 patients who relapsed, allowing earlier treatment with immunotherapy, resulting in PET remissions all 7 patients, 3 without CT or clinical relapse. There were no cases of CT relapse before PET relapse. The use of regular PET scanning therefore altered therapy (either delayed or initiated immunotherapy) in 10/27 (37%) evaluable patients in this study. The use of PET scans in identifying early relapse in patients undergoing RIT for lymphoid malignancies, where early DLI can be beneficial is very promising and needs further evaluation, with larger event numbers and longer follow-up.