Role of PET/CT Assesment before Autologous Stem Cell Transplantation in Relapsed or Refractory Lymphoma Patients
Authors: de la Cruz Vicente Fátima , Domiunguez Muñoz Maria Angeles , Carrillo Cruz Estrella , Márquez Malaver José Francisco , Parody Porras Rocio , Falantes González Jose Francisco , Calderón Cabrera Cristina , Pérez López Olga , Solé Rodríguez María , González Campos Jose , Montero Cuadrado María Isabel , Martino Galiana María Luz , Pérez-Simón Jose Antonio , Espigado Ildefonso 
Published: October 2019

Abstract
BACKGROUND : Approximately 20 to 55% of patients diagnosed with lymphoma will relapse or show refractoriness after first line treatment. Salvage chemotherapy and autologous stem cell transplantation (ASCT) is the most commonly used approach in patients with chemosensitive disease. Nevertheless, active disease at the time of ASCT evaluated by PET/CT is correlated with a poor overall survival (OS). Despite this, it is not definitively established whether or not; tumor burden assessed by PET/CT at time of ASCT affects the outcome of these patients.
OBJECTIVES: To analyze the predictive value of PET/CT performed before ASCT in terms of progression free survival (PFS) and overall survival (OS) among patients diagnosed with relapsed/refractory lymphoma with active disease at time of transplant.
PATIENTS AND METHODS: Retrospective study of all consecutive patients diagnosed with relapsed or refractory lymphoma after at least one line of chemotherapy and who had active disease assessed by PET/CT at the time of ASCT between July/2001 and August/2012 in our institution. Partial response (PR) ≥ 90%, was defined as a decrease in tumor load higher that 90% as assessed by PET/CT without fulfilling criteria of complete response. Partial response was defined as a decrease in tumor load higher than 50% and lower than 90%. Progressive disease was defined as appearing new focus of disease or worsening previous involved areas. OS was analyzed by Kaplan-Meier test and “log rank test” was used to compare different groups (PR ≥ 90% vs PR or less). PFS was analyzed with “Cox Regression” test.
RESULTS: Demographics and clinical data are summarized in table 1. Seven years PFS of patients with partial response ≥ 90% at ASCT was 71.4% versus 28.6% for patients in PR or less at transplant (p=0.09). Among patients who develop it median time to relapse or progression after ASCT was 4 months (1-40). ASCT related mortality was 3.4%. Rescue therapy after transplant consisted on chemotherapy in 71.4% of cases, radiotherapy in 19% and supportive care in 9.5%. Eight patients underwent allogeneic stem cell transplantation after ASCT (27.6%). After 18 months median follow-up (3-69), OS for the whole series was 48.3% at seven years. Patients who achieved PR ≥ 90% had a seven year OS of 72.7% versus 33.3% among patients with PR or less[HR 3.1 (CI 95% 0.9-11.4), p=0.05].
CONCLUSIONS
1) Patients with pre-ASCT PET/TC evaluation defined as ≥ 90% PR have a long term disease free and overall survival.
2) Conversely, patients receiving ASCT in a partial response lower than 90% have a poor long term disease free and overall survival, suggesting that this set of patients should be candidates to alternative therapeutic options such as first-line Allo-SCT or investigational drugs.
TABLE 1. Patients characteristics N=29 Age, median (range) 34 (27-51) Sex M/F :58.6% / 41.4% DiagnosticHLNHLDLBC-LMantle cell lymphomaPeripheral T cell lymphomaLymphoblastic lymphomaTransformed follicular lymphoma 48.3% 51.7% 60% 13.3% 13.3% 6.7% 6.7% Ann Arbor stageIIIIIIIV 3.4% 37.9% 24.1% 34.5% Prognosis index (IPI,EORTC/IH)Low riskIntermediate riskHigh risk 10.7% 42.9% 46.4% Bulky mass 35.7% Extranodal disease 42.9% B symptoms 50 % Bone marrow involvement 7.1% Number of previous line therapy 3 (2-5) Previous response to treatmentPR≥90%PR or less 37.9% (n=11) 62.1% (n=19) Status disease at ASCTPrimary refractory diseaseRelapse after previous response 55.2% 44.8% Conditioning regimenBEAMBCNU + TTBCNU + TT + CY 93.1% 3.4% 3.4%
HL: Hodgkin lymphoma; NHL: non-hodgkin lyphoma; DLBC Lymphoma: diffuse large B cell lymphoma; IPI: International Prognostic Index; IH: Hansenclever index; BEAM: Busulfan, etoposide, cytarabine, melphalan; TT: Thiotepa; CY: cyclophosphamide.

Disclosures
No relevant conflicts of interest to declare.