Diagnostic cell of origin was not associated with overall survival in patients with diffuse large B-cell lymphoma (DLBCL) with relapsed/refractory disease, according to a study published in Hematological Oncology.

The cell of origin determined either by immunohistochemistry using Han’s criteria or gene expression profiling (GEP) was not found to be significantly associated with overall survival after the first relapse of DLBCL. 

The 2-year overall survival of patients with germinal center B-cell (GCB) type was similar to those with nonGCB type DLBCL (45% vs 44%). The subset of patients with activated B-cell (ABC) type was also not significantly different from GCB type (42% vs 45%). Patients whose genetic signatures did not match GCB or ABC were unclassified and had a 2-year overall survival of 54%, which trended toward being higher but was not significant.

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While cell of origin did not appear to impact overall survival in patients, those with double-hit lymphoma (DHL) or double-expressor lymphoma (DEL) did have significantly worse outcomes. DHL patients had 2-year overall survival of 16% compared to 51% in nonDHL patients (P <.0001). Patients with DEL also had worse outcomes, with 2-year overall survival of 33% compared to 50% in nonDHL/nonDEL patients (P <.014).

“Cell of origin at diagnosis by IHC or GEP did not impact outcome of relapsed/refractory DLBCL while DHL and DEL status were associated with worse outcomes in relapsed/refractory setting. Hence, evolving molecular signatures of DLBCL beyond cell of origin and interaction with [tumor microenvironment] may be more important drivers of pathophysiology of relapsed/refractory DLBCL,” the authors said.

A total of 373 patients with DLBCL were recruited for the study between September 2002 and June 2015. Of these patients, 278 had cell of origin determined by IHC and were found to include 152 GCB patients and 107 nonGCB patients. Cell of origin by GEP was performed in 140 patients and found 44 ABC, 65 GCB, and 13 unclassifiable patients.

Fluorescence in situ hybridization data were available for 163 patients and found 19 (12%) of patients had DHL. Protein expression data were available for 135 patients, and 30 (22%) were found to have DEL.


Desai SH, Mwangi R, Smith AN, et al. Cell of origin is not associated with outcomes of relapsed or refractory diffuse large B cell lymphoma. Hematol Oncol. Published online October 28, 2022. doi:10.1002/hon.3098