The Role of PET Scanning in Directing Immune Manipulations Following Reduced Intensity Transplants in Adults with Lymphoid Malignancies.
Authors: Cooper N. , Avivi I. , Peggs K. , Hart D. , Thomson K. , Goldstone A. , Linch D. , Ell P. , Bomanji J. , Mackinnon S. 
Published: October 2019

Abstract
FDG PET scanning provides useful information that is now being integrated into treatment algorithms for patients with lymphomas. Its use in relation to allogeneic transplantation has not been assessed. 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. Methods: All patients referred to University College Hospital from May 2002 with lymphoid malignancies, suitable for RIT were invited to participate. Patients had PET and CT scans pre-RIT and at 3, 6, 9, 15 and 24 months post RIT. Patients were conditioned with fludarabine and melphalan and in vivo T cell depletion with alemtuzumab. Ciclosporin was given from day −1 to 3 months after RIT. Initial management for positive imaging was withdrawal of immune suppression. 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: 29 patients, median age 44 years (range 20 to 64 years) entered the study; 24 (6 Hodgkin lymphoma (HL), 2 Mantle cell (MC), 16 Non-Hodgkin Lymphoma (NHL)) are evaluable with > 3 months follow-up. 13 of 24 had positive PET scans before RIT, 9 had negative scans and 2 were not scanned before RIT. Of the 13 patients who had positive PET scans, there were 3 transplant related mortalities: CMV pneumonitis (n=1, HL), severe GVHD (n=2, NHL). The 10 remaining patients with positive PETs pre-RIT have a median 10.5 months follow up (range 6 to 24 months). 9 of 10 patients had a response to RIT (7CR and 2PR). Subsequently 5 of these 10 have relapsed/progressed at 6 to 9 months from RIT. Two were treated by withdrawal of immune supression. Both developed GVHD and died of progressive disease. 3 were treated with DLI. One patient (NHL) responded 3 months after 1 x106/kg, one (MC) after 1 x 107/kg and the third (NHL) showed a CR following both 1 x 107/kg and rituximab given for immune cytopenia. The remaining 5 patients (1HL, 4NHL) with positive pre-RIT PET scans remain in remission a median of 9 months (range 6 to 15 months) after RIT. One of 9 patients (NHL) with negative pre-RIT PET scans had progression of disease at 9 months, treated with escalating DLI up to 1 x 107/kg with no response. The remaining 8 patients with negative pre-RIT PET scans have remained in CR a median of 9 months (range 3 to 24 months) from RIT. One patient who did not receive pre-RIT scan died at 9 months of GVHD without evidence of disease progression. The second progressed at 12 months and is awaiting biopsy. 6 patients had nodes on CT scan of unclear significance, with negative PET scans. One of these patients has subsequently relapsed. The remaining patients continue in CR. 3 patients have had positive PET scans and received DLI 3 to 6 months before positive CT findings. This study suggests that PET imaging provides additional information beyond that available from CT scanning aiding patient management including earlier intervention (n=3) and deferring unnecessary treatment (n=6). 3/4 patients receiving DLI have responded. Positive PET scanning pre-RIT was associated with inferior outcome but does not preclude CR (6/13). Further follow-up and larger event numbers are required to establish the role of PET imaging in modulating treatment following RIT in patients with lymphoid malignancies.