Positive Pre-Transplantation ^[18-F] FDG-PET Is Not a Barrier to Successful Allograft Outcomes in Chemosensitive Hodgkin Lymphoma

Abstract 2016

Positron emission tomography (PET) scanning is increasingly recognised to provide important prognostic information in patients with Hodgkin Lymphoma (HL) receiving chemotherapy or undergoing autologous stem cell transplantation. Its role in defining outcomes following allogeneic transplantation is less clear. We previously examined the outcomes of patients with chemosensitive lymphoma undergoing alemtuzumab-based allogeneic transplantation, and found pre-transplantation PET-CT status to have no influence on post-transplant outcomes (non-relapse mortality (NRM), relapse incidence (RI), overall survival (OS), or progression-free survival (PFS)). The numbers of patients with specific histological diagnoses were relatively small, limiting the power of subgroup analyses, and within the HL group (n=20) only 8 had metabolic complete response (mCR) prior to transplant. We now have experience of 80 patients aged 12–59 with HL undergoing alemtuzumab-based allogeneic transplantation in whom we have pre-transplantation PET data. A visual analysis using a 5-point scale was employed with a threshold of 3 or above considered positive. The development of new FDG-avid lesions scoring 3–5 in the absence of other potential causative pathologies, or significant increase in SUV of over 25% in previously positive lesions was considered compatible with relapse/progression and an indication for donor-lymphocytes following transplantation. Biopsies were performed in the former where feasible, and repeat PET-CT studies at 6–8 weeks in equivocal cases where biopsy was not possible prior to administration of donor-lymphocytes. 23 patients had negative PET studies prior to transplantation, and 57 patients had positive PET studies. 10 of the latter had progressive disease at the time of transplant. Donors were HLA-matched related in 40, HLA-matched unrelated in 28 and HLA-mismatched unrelated in 12. Within the non-progressive group (n=70) there were no significant differences according to PET status (PET- vs PET+) in either 3yr NRM (23% vs 15%) or relapse incidence (21% vs 30%, p=0.3223). The corresponding values for the progressive group were 40% and 50% respectively, reaching statistical significance only in relapse incidence for PET- vs progressive (p=0.0324), with a trend in the same direction for PET+ vs progressive (p=0.1199). Similarly, there were no significant differences within the non-progressive group according to PET status in terms of 3yr OS (77% vs 64%, p=0.5486), PFS (56% vs 52%, p=0.5631) or ‘current’ PFS (incorporating post donor-lymphocyte salvage responses in those treated for relapse (n=15); 73% vs 66%, p=0.7235), whilst all 3 were significantly worse in the progressive group (33%, 10% and 10% respectively, p=0.0001-0.0055). Within the non-progressive group there was no impact of donor source on survival outcomes (3yr OS 67% vs 70%, p=0.9496; PFS 58% vs 50%, p=0.3236, cPFS 68% vs 69%, p=0.8587 for related vs unrelated donors respectively). NRM was equivalent (18% vs 17%), as was relapse incidence (20% vs 33%). Within the non-progressive group the median number of prior lines of therapy was 4 (range 2–9), but interestingly outcomes were not influenced by number of prior lines when evaluated by less than 4, 5 or 6 compared to the remainder e.g. NRM 17% vs 18%, relapse incidence 26% vs 29% for 4 or fewer vs more than 4. Our data suggest that patients with progressive disease pre-transplant have particularly poor outcomes, but that within the non-progressive group the presence of residual FDG-avid disease pre-transplant has no significant influence on post-transplant outcomes using alemtuzumab-based T-cell depleted regimens. The results now deliverable with this strategy incorporating post-transplant PET-CT surveillance and aggressive intervention with donor-lymphocytes remain very encouraging in all non-progressive patients (63% 5yr cPFS) regardless of donor source. Outcomes appear no worse according to number of prior lines as long as the disease is non-progressive at the time of transplantation, suggesting that multiple lines of salvage are warranted to establish chemosensitivity if the patient remains fit enough, but that there may be little advantage in pursuing mCR with additional lines prior to transplantation in those that show a response.