Abstract
Background: Conversely to what has been reported for autotransplant,most studies have shown that pre-transplant Fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) status does not appear to predict survival after allogeneic stem cell transplantation (Allo-SCT) for lymphoma patients. However it is less clear what is the impact of early FDG-PET status on outcomes after Allo-SCT, especially when using Deauville 5-point scale (DS) which has become a standard of care for staging and re-staging of FDG-PET.
Methods: This retrospective study included all lymphoma patients who underwent FDG PET before and/or early after Allo-SCT in our institution and who were alive at least 3 months after the graft. The primary objective was to study the impact on OS and LFS of pre-transplant (within 1 month) and early post-transplant (+3 months and within +6-9 months) FDG PET in these patients. All FDG-PET were reviewed by a nuclear medicine expert and restaging was performed according to 5-point DS. Two thresholds of positivity were used: a score of at least 3 (DS3, i.e. scores 3 - 5) and a score of at least 4 (DS4, i.e. score of 4 or 5).
Results: Between April 2005 and December 2015, 103 patients fulfilled the inclusion criteria. There were 69 males (66%) and the median age was 51.6 years old (range: 22-67). Forty-seven patients had high-grade non-Hodgkin lymphoma (NHL), 6 low-grade NHL, 34 T-cell lymphoma and 16 Hodgkin lymphoma. Most patients were considered in complete remission at the time of transplant (n=56) and received a reduced-intensity conditioning regimen (n=90). The numbers of patients with available FDG PET before transplant, at 3 months and between 6-9 months post-transplant were 81, 93 and 61, respectively. Deauville FDG PET staging identified 29 DS3 and 20 DS4 patients before transplant, 28 DS3 and 20 DS4 at 3 months, and 25 DS3 and 18 DS4 between 6-9 months post-transplant, respectively.
With a median follow-up of 49.5 months (range: 6-140.5) for alive patients, 3-year OS and LFS were 81% (71-87) and 65% (54-74) for the whole cohort, respectively. Twenty-six patients relapsed at a median time of 4.5 months (range: 2.9-15.9) from Allo-SCT.
In univariate analysis, only the post-transplant FDG-PET status influenced outcomes. Factors associated with a lower OS were DS3 and DS4 scores at 3 months (HR: 2.25; 95%CI: 0.93-5.44, p=0.07 and HR: 3.00; 95%CI: 1.22-7.36, p=0.01, respectively) and a DS3 score between 6-9 months post-transplant (HR: 4.08; 95%CI: 1.00-16.55, p=0.04). Factors associated with a lower LFS were DS3 and DS4 scores at 3 months (HR: 2.64; 95%CI: 1.30-5.39, p=0.007 and HR: 3.86; 95%CI: 1.86-8.02, p=0.0003, respectively) as well as between 6-9 months (HR: 4.20; 95%CI: 1.26-13.98, p=0.01 and HR: 2.72; 95%CI: 0.86-8.60, p=0.08) post-transplant.
In multivariate analysis, DS4 FDG-PET at 3 months was the only independent factor associated with lower OS (HR 2.8; 95%CI: 1.13-6.97), p=0.0269) and LFS (HR 2.44, 95%CI: 0.94-6.33, p=0.06).
Total body CTscan evaluation was performed in 16/28 and 14/25 DS3 patients at 3 months and between 6-9 months post-transplant, respectively. At 3 months, all CT-scans were considered normal while 4/14 were considered positive between 6-9 months. Lymph nodes biopsies were performed for 8/25 DS3 patients at 3 months showing 6 lymphoma relapses (75%) and for 7/25 DS3 patients between 6-9 months post-transplant showing 2 lymphoma relapses (29%). Six patients received donor lymphocyte infusion between 3 to 9 months post-transplant, only 2 being guided by FDG-PET.
Conclusion: A DS4 FDG-PET status at 3 months is highly predictive of survivals in lymphoma patients receiving an Allo-SCT and may help to guide strategies to prevent relapse. These results have to be validated prospectively.
Touzeau: AbbVie: Research Funding. Moreau: Bristol-Myers Squibb: Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Celgene: Consultancy, Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria.
Author notes
Asterisk with author names denotes non-ASH members.