Table 1.

Parameters associated with outcome in DLBCL patients treated with R-CHOP or R-CHOP-like regimens

AntigensPathwaysOncogenesImagingOthers
PFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReference
HLA-G polymorphism Short OS (for poor-risk patient) 38 High p-AKT expression Shorter PFS and OS 39 Double-hit lymphoma  3 PET at end of treatment; 7%-20% relapse rate  40 CD5+ PFS, 40%; OS, 65% 41 
CXCR4 expression, particularly if associated with BCL2 translocation Shorter PFS in GCB 42 Older age and male sex associated with JUN and CYCS signaling Shorter PFS and OS 43 TP53 mutation plus MIR34A methylation, rare (6%) but very aggressive  44 Tumor necrosis at diagnosis High correlation with PFS and OS 45 Anemia and high CRP at diagnosis Shorter PFS and OS 46 
Ki-67 >80% Shorter PFS and OS 47 11-gene STAT3 activation signature Shorter OS and EFS 48 Isolated MYC abnormalities not associated with outcome Other studies had shorter PFS and OS 7 Interim PET positivity Shorter PFS, but not in all studies 49, 50 High CXCL 10 Shorter EFS and OS 51 
High serum sIL-2R Shorter PFS and OS 52, 53 High miR-155 expression; R-CHOP failure  54 RCOR1 deletion and RCOR1 loss-associated signature Shorter OS 55 ΔSUVmax <83% Shorter PFS and OS 56 Occult BM involvement Shorter PFS and OS (similar to BM-positive) 57 
High serum sCD27 Shorter OS 58 CDKN2A loss Shorter OS 59 High expression of BCL2,
particularly with low-risk IPI 		Shorter PFS and OS 9 Sarcopenia on CT scan Shorter OS 60 Low serum albumin level (<35 g/L) 5-y PFS, 51%; OS 53% 61 
High serum IL-18 Shorter PFS and OS 62 DAPK1 promoter methylation Shorter OS and DFS 63 MYC-Ig gene translocation Shorter PFS and OS 64 High metabolic tumor volume Shorter OS 65 Vitamin D deficiency Shorter EFS and OS 66 
High VEGFR2 expression Shorter OS 67 High EZH2 expression Longer OS 68 TNFAIP3 and GNA13 mutations Shorter OS in ABC lymphoma 69    Cachexia score Shorter PFS and OS 70 
CD30 positivity Shorter EFS and OS 71 High slug expression Longer PFS and OS 72 Double-protein level expression Shorter PFS and OS 73, 74    Concordant BM involvement Shorter PFS and OS 75 
Low HLA-DR expression Shorter OS 76 High ZEB1 expression Shorter OS 72 Low miR-129-5p expression Shorter OS 77    Abnormal IgMκ:IgMλ ratio Shorter PFS 78 
C1qA A/A allele Longer OS 79 High Trx-1 expression Shorter OS 80 MYC overexpression Shorter OS 4    Stage III or tumor >5 cm; increased local recurrence  81 
MET-RON phenotype Shorter OS 82 TP53 pathway dysregulation Shorter PFS and OS 83 Homozygous STAT3 phenotype Longer OS 84    Worse pretreatment QoL Shorter OS 85 
High survivin expression Shorter OS 86 High miR-34A expression; higher response to doxorubicin  87 High BCL2 expression Shorter PFS and OS 88    High neutrophil: lymphocyte ratio Shorter PFS and OS 85 
Higher PRAME expression Shorter PFS 90 p52/RELB expression Longer PFS and OS 91 MYC and BCL2 copy number aberrations Shorter PFS and OS 92    Low CD4+ TILs Shorter PFS and OS 93 
High β2-microglobulin Shorter PFS and OS 94 Epigenomic heterogeneity; higher early relapses  12 High GSTP1 and TOPO2α Shorter PFS and OS 95    Low ALC/AMC ratio Shorter PFS and OS 96 
High BiP/GRP78 expression Shorter OS 97 High S1PR1 and S1PR1/pSTAT3 expression Shorter OS 98 Loss of SLC22A16 (doxorubicin transporter); higher early relapses  99    EBV-positive (high EBER expression) Shorter PFS and OS 100 
High sTNFR2 Shorter PFS and OS 101 High LincRNA-p21 Longer PFS and OS 102 MLH1 AG/GG genotype;
higher early progression 		Shorter OS 103    Increased TAMs (CD68+ cells) Longer OS 104 
High miR-224 expression Shorter PFS and OS 105 Low GILT expression Shorter OS 106 del(8p23.1) Shorter OS 107    Increased M2 (CD163+ cells) Shorter PFS and OS 104 
REV7 expression Shorter PFS and OS 108 Serum miRNA signature; increased early progression  109 p53 deletion or mutations Shorter PFS 110    Immunoblastic morphology Shorter EFS and OS 111 
Circulating tumor DNA; higher relapse rate  112 Low HIP1R expression Shorter PFS and OS 113 FOXP1 expression Shorter OS 114    High CRP level Shorter PFS and OS 115 
Higher sPD-L1 protein Shorter OS 116 High miR-125b and miR-130a; high risk of failure  117 TP53 G/G genotype; high failure rate  117    Comorbidity Shorter OS 118 
High CD59 expression Shorter PFS and OS 119 Increased UCH-L1 in GCB-DLBCL; early relapse  120 Wild-type TP53 Longer OS 117    Male sex Shorter OS 121 
BAFF-R expression;
higher CR rate 		Longer PFS and OS 122 NF-kB mutations such as NFKBIE and NFKBIZ; increased relapses  14 STAT6 mutations; increased relapses  14       
High sIL-2R; increased early relapse  53             
Low CD20 expression Shorter EFS and OS 123             
AntigensPathwaysOncogenesImagingOthers
PFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReferencePFS/OS/EFSReference
HLA-G polymorphism Short OS (for poor-risk patient) 38 High p-AKT expression Shorter PFS and OS 39 Double-hit lymphoma  3 PET at end of treatment; 7%-20% relapse rate  40 CD5+ PFS, 40%; OS, 65% 41 
CXCR4 expression, particularly if associated with BCL2 translocation Shorter PFS in GCB 42 Older age and male sex associated with JUN and CYCS signaling Shorter PFS and OS 43 TP53 mutation plus MIR34A methylation, rare (6%) but very aggressive  44 Tumor necrosis at diagnosis High correlation with PFS and OS 45 Anemia and high CRP at diagnosis Shorter PFS and OS 46 
Ki-67 >80% Shorter PFS and OS 47 11-gene STAT3 activation signature Shorter OS and EFS 48 Isolated MYC abnormalities not associated with outcome Other studies had shorter PFS and OS 7 Interim PET positivity Shorter PFS, but not in all studies 49, 50 High CXCL 10 Shorter EFS and OS 51 
High serum sIL-2R Shorter PFS and OS 52, 53 High miR-155 expression; R-CHOP failure  54 RCOR1 deletion and RCOR1 loss-associated signature Shorter OS 55 ΔSUVmax <83% Shorter PFS and OS 56 Occult BM involvement Shorter PFS and OS (similar to BM-positive) 57 
High serum sCD27 Shorter OS 58 CDKN2A loss Shorter OS 59 High expression of BCL2,
particularly with low-risk IPI 		Shorter PFS and OS 9 Sarcopenia on CT scan Shorter OS 60 Low serum albumin level (<35 g/L) 5-y PFS, 51%; OS 53% 61 
High serum IL-18 Shorter PFS and OS 62 DAPK1 promoter methylation Shorter OS and DFS 63 MYC-Ig gene translocation Shorter PFS and OS 64 High metabolic tumor volume Shorter OS 65 Vitamin D deficiency Shorter EFS and OS 66 
High VEGFR2 expression Shorter OS 67 High EZH2 expression Longer OS 68 TNFAIP3 and GNA13 mutations Shorter OS in ABC lymphoma 69    Cachexia score Shorter PFS and OS 70 
CD30 positivity Shorter EFS and OS 71 High slug expression Longer PFS and OS 72 Double-protein level expression Shorter PFS and OS 73, 74    Concordant BM involvement Shorter PFS and OS 75 
Low HLA-DR expression Shorter OS 76 High ZEB1 expression Shorter OS 72 Low miR-129-5p expression Shorter OS 77    Abnormal IgMκ:IgMλ ratio Shorter PFS 78 
C1qA A/A allele Longer OS 79 High Trx-1 expression Shorter OS 80 MYC overexpression Shorter OS 4    Stage III or tumor >5 cm; increased local recurrence  81 
MET-RON phenotype Shorter OS 82 TP53 pathway dysregulation Shorter PFS and OS 83 Homozygous STAT3 phenotype Longer OS 84    Worse pretreatment QoL Shorter OS 85 
High survivin expression Shorter OS 86 High miR-34A expression; higher response to doxorubicin  87 High BCL2 expression Shorter PFS and OS 88    High neutrophil: lymphocyte ratio Shorter PFS and OS 85 
Higher PRAME expression Shorter PFS 90 p52/RELB expression Longer PFS and OS 91 MYC and BCL2 copy number aberrations Shorter PFS and OS 92    Low CD4+ TILs Shorter PFS and OS 93 
High β2-microglobulin Shorter PFS and OS 94 Epigenomic heterogeneity; higher early relapses  12 High GSTP1 and TOPO2α Shorter PFS and OS 95    Low ALC/AMC ratio Shorter PFS and OS 96 
High BiP/GRP78 expression Shorter OS 97 High S1PR1 and S1PR1/pSTAT3 expression Shorter OS 98 Loss of SLC22A16 (doxorubicin transporter); higher early relapses  99    EBV-positive (high EBER expression) Shorter PFS and OS 100 
High sTNFR2 Shorter PFS and OS 101 High LincRNA-p21 Longer PFS and OS 102 MLH1 AG/GG genotype;
higher early progression 		Shorter OS 103    Increased TAMs (CD68+ cells) Longer OS 104 
High miR-224 expression Shorter PFS and OS 105 Low GILT expression Shorter OS 106 del(8p23.1) Shorter OS 107    Increased M2 (CD163+ cells) Shorter PFS and OS 104 
REV7 expression Shorter PFS and OS 108 Serum miRNA signature; increased early progression  109 p53 deletion or mutations Shorter PFS 110    Immunoblastic morphology Shorter EFS and OS 111 
Circulating tumor DNA; higher relapse rate  112 Low HIP1R expression Shorter PFS and OS 113 FOXP1 expression Shorter OS 114    High CRP level Shorter PFS and OS 115 
Higher sPD-L1 protein Shorter OS 116 High miR-125b and miR-130a; high risk of failure  117 TP53 G/G genotype; high failure rate  117    Comorbidity Shorter OS 118 
High CD59 expression Shorter PFS and OS 119 Increased UCH-L1 in GCB-DLBCL; early relapse  120 Wild-type TP53 Longer OS 117    Male sex Shorter OS 121 
BAFF-R expression;
higher CR rate 		Longer PFS and OS 122 NF-kB mutations such as NFKBIE and NFKBIZ; increased relapses  14 STAT6 mutations; increased relapses  14       
High sIL-2R; increased early relapse  53             
Low CD20 expression Shorter EFS and OS 123             

The table represents a summary of studies published during the last 5 years.

ABC, activated B cell; BM, bone marrow; CR, complete response; CRP, C-reactive protein; CT, computed tomography; EBV, Epstein-Barr virus; GCB, germinal center B-cell; IL-18, interleukin-18; IPI, International Prognostic Index; Ig, immunoglobulin; miRNA, microRNA; NF-kB, nuclear factor kB; PET, positron emission tomography; QoL, quality of life; TAM, tumor-associated macrophage; TIL, tumor-infiltrating lymphocyte; ΔSUVmax, maximum change in standardized uptake value.

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