DISCUSSION
metabolic tumor, tumor, high‐intermediate, toxicity, DLBCL, DEL DLBCL, lymphomas, DSHNHL
TUMOR, REMISSIONS, PROLIFERATION, DISEASE, LYMPHOMAS, DEL
The role of upfront auto‐HSCT in DLBCL remains controversial. EBMT (level of evidence 1)These statements are based on the results of RCT. The improvement of 2‐year FFS (In NCT00355199,SWOG‐S7904 trialOn the other hand, DSHNHL 2002‐1 trial demonstrated only increased toxicity in the HDCT group without survival benefit.Meta‐analysesPFS benefit in high‐intermediate and high‐risk DLBCL patients (Our study demonstrated the positive role of upfront auto‐HSCT in the survival of stage IV DLBCL NOS high/high‐intermediate IPI risk patients.The key point of this study was patient selection. Most previous trials included all types of B‐cell and even T‐cell lymphomas.The decision to perform upfront auto‐HSCT in the described group (Trial arms were completely balanced in all characteristics. A higher proportion of bulky disease in the upfront group is not clinically significant because it does not always correspond with high metabolic tumor volume, calculated by PET‐CT.In this trial, PET‐CT was done once in 71% (25/35) upfront patients and 41% (29/70) of control patients. PET scans before and after the treatment had only 23% (8/35) upfront patients and 17% (12/70) control patients. The number of remissions, evaluated only by CT and biopsy was 40% (14/35) in the upfront and 59% (41/70) in the control group. Low incidence of PET resulted from the scarce of original PET scans and the lack of PET in Russia in the early 2010's.The achievement of CR is the main goal of treatment. Partial responses are considered treatment failure and recommended to manage as a refractory disease.The association of DEL and inferior survival (No difference was estimated between R‐CHOP/upfront and intensive ICT (3‐year RFS 75% vs. 86% respectively, Another trial targeted DEL DLBCL patients with elevated LDH treated by upfront HDCT.In our trial, DEL significantly decreased 3‐year PFS (The non‐GCB COO subtype is usually associated with poor prognosis in DLBCL.A high proliferation index (Ki67) is generally considered a negative prognostic marker in B‐cell lymphomas. A meta‐analysis,The high amount of CD3(+) tumor‐infiltrating lymphocytes (TILs), assessed by immunohistochemistry (IHC), is associated with favorable outcomes in advanced stage DLBCL,It is an interesting result about the superiority of DA‐EPOCH‐R over R‐CHOP in our trial because randomized trials did not find any survival benefit in advanced‐stage DLBCL, treated by DA‐EPOCH‐R.Another controversial result was the influence of unexplained loss of >10% of body weight (High level of LDH associated with poor prognosis and predicts survival in DLBCL patients.This study had several limitations. Firstly, it was retrospective, and the patient selection wasn't randomized. However, strict selection criteria were applied, therefore trial arms were completely balanced. Secondly, we did not use the gene expression profile (GEP) based molecular classification because of the absence of GEP in our institution, and were limited in FISH for financial reasons. Also, there were several missing IHC data, that limited the inclusion of IHC parameters in calculations. And thirdly, because of limited PET data, modern PET‐based predictors like metabolic tumor volume or tumor lesion glycolysis were not analyzed.In conclusion, the upfront auto‐HSCT is still under investigation. Further trials are needed to better select the target group of this treatment option.