The Predictive Significance of Early Metabolic Remission Post Autologous Hematopoietic Transplantation in Lymphomas Conditioned with Either BEAM or a Busulfan-Based Regimen
Authors: Sakellari Ioanna , Mallouri Despina , Constantinou Varnavas C , Iskas Michail , Batsis Ioannis , Papadimitriou Stergios , Panteliadou Kira , Palladas Panayiotis , Datseris Ioannis , Anagnostopoulos Achilles 
Published: October 2019

Abstract
Fluorine-18-Deoxyglucose Positron Emission Tomography Scan (PET) is a valuable diagnostic tool in many histologic types of lymphomas, with an increasing prognostic role for both pre- and post-treatment disease assessment. In the autologous haematopoietic cell transplantation (AHCT) setting, the prognostic value of pre-AHCT PET has been established by current studies, but the significance of early post-treatment PET negativity has not yet been fully investigated.
In this retrospective, single center analysis, we evaluated the role of early post-AHCT (+3 to +6 months) metabolic remission in 98 consecutive lymphoma patients (pts), 60 males and 38 females, with Hodgkin (58, HL) and non-Hodgkin (40, NHL) lymphoma, aged 36 (13-66) years, who underwent high dose chemotherapy followed by autologous stem cell rescue, during the years 2009-2014. The conditioning regimen was either BEAM in 29, or Busulfan-based in 69 pts (Busulfan 9.6mg/kg/d×3d, Etoposide 400mg/m2/d×2d and Melphalan 140mg/m2, BuEM). The pts underwent AHCT for primary refractory (65), or relapsed disease (28) post 3 (1-9) lines of treatment, or as consolidation in first complete remission (5). The pre-AHCT disease status was chemosensitive in 53 pts, including 24 in complete remission (CR) post salvage therapy as evaluated by CTs or/and PET. Seventy seven pts were evaluated by PET at +3 to +6 months while the rest had disease progression by CT assessment after AHCT (7 pts received additional involved field irradiation post-AHCT, as part of the treatment plan). Sixty pts had negative and 17 positive PET in early post-transplant evaluation. The overall response rate at +3 months post-AHCT was 68% (66 of 96 evaluated pts), including 60% (58 pts) in complete remission. With a median follow up of 29 (2 - 76) months (BEAM 18 months, BuEM 45 months), the estimated 5-year disease free survival (DFS) and time to progression (TTP) were similar in both conditioning regimens. Relapse rate was 17% vs 21% in BEAM and BuEM, respectively. At last follow-up 73 (75%) pts were alive and 58 (61%) in CR. Treatment related mortality was low with both regimens (1%). Patients' characteristics according to the conditioning regimen were similar in terms of disease (HL, NHL), disease phase (CR, partial response, stable, progression) and chemosensitivity (x2 test). In HL pts, OS was high and similar in both conditioning groups, with no significant difference in TTP. Similarly, in NHL pts the OS, DFS and TTP were not significantly different in the two groups. In multivariate analysis, disease (HL, NHL), disease phase, chemosensitivity, type of conditioning regimen and early-PET were incorporated. In the whole cohort of pts, favorable factors in terms of OS were HL and early PET-negativity (p=0.02 and p=0.01, respectively), while for TTP chemosensitivity and early PET-negativity (p=0.009 and p=0.006, respectively). In HL pts, early PET-negativity was the only significant factor for superior OS (p=0.02), maintaining a borderline significance with respect to TTP (p=0.06) and disease chemosensitivity (p=0.02). In NHL pts the single significant factor for superior TTP was early PET-negativity (p=0.03).
With the limitations of this retrospective analysis, early metabolic complete remission, along with disease chemosensitivity to salvage treatment, seems to be a significant favorable factor in both Hodgkin and NHL pts for improved overall survival and time to disease progression. Additionally, in this study group of pts, both conditioning regimens proved to be similarly efficacious and feasible, remaining the key players for a successful outcome of AHCT in lymphomas.

Disclosures
No relevant conflicts of interest to declare.