Presence of autoimmune disease affects not only risk but also survival in patients with B-cell non-Hodgkin lymphoma

Geffen Kleinstern, Mor Averbuch, Rania Abu Seir, Riki Perlman, Dina Ben Yehuda, Ora Paltiel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Although autoimmune diseases (AIDs) are known to predispose to non-Hodgkin lymphoma (NHL), their association with NHL prognosis has rarely been investigated. We examined associations between autoimmunity and B-cell NHL onset by comparing AID history (determined by self-report and medication review and supplemented by chart review where possible) among 435 adult B-NHL patients in Hadassah-Hebrew University Medical Center, diagnosed 2009-2014, and 414 age-and-sex frequency-matched controls. We examined AIDs as a whole, B- and T-cell–mediated AIDs, and autoimmune thyroid diseases. Among cases, we used Kaplan-Meier and Cox regression models to assess the association of AID with overall survival and relapse-free survival, adjusting for prognostically important patient and disease characteristics such as Ki67% staining, International Prognostic Index, rituximab treatment, and histological subgroup. Autoimmune diseases were associated with B-NHL (odds ratio [OR] = 1.95; 95% confidence interval (CI), 1.31-2.92), especially AIDs mediated by B-cell activation (OR = 5.20; CI, 1.90-14.3), which were particularly associated with marginal zone lymphoma (OR = 19.3; CI, 4.59-80.9). We found that time to relapse for all B-NHL patients with AIDs was significantly shorter (mean of 49.21 mo [±3.22]) than among patients without AID (mean of 59.74 mo [±1.62]), adjusted hazard ratio [HRadj] = 1.69 (CI, 1.03-2.79). Specifically, in patients with diffuse large B-cell lymphoma, of whom 91.8% had received rituximab, a history of B-cell–mediated AIDs was associated with shorter relapse-free survival and overall survival, HRadj = 8.34 (CI, 3.01-23.1) and HRadj = 3.83 (CI, 1.20-12.3), respectively. Beyond confirming the well-known association between AIDs and B-NHL, we found that AID is an adverse prognostic factor in B-cell lymphoma, associated with a shortened time to relapse, suggesting that there are specific therapeutic challenges in the subgroup of patients suffering from both these diseases. Further work is required to address mechanisms of resistance to standard treatment in the setting of AID-associated B-NHL. In the era of immunotherapy, these findings have particular relevance.

Original languageAmerican English
Pages (from-to)457-462
Number of pages6
JournalHematological Oncology
Issue number2
StatePublished - Apr 2018
Externally publishedYes

Bibliographical note

Funding Information:
Hadassah University Hospital Compensatory Fund; Israel Science Foundation (ISF), Grant/ Award Number: 877/10; United States Agency for International Development (USAID)/MERC, Grant/Award Number: TA‐ MOU‐11‐M31‐025

Funding Information:
This study was made possible by the generous support of the American people through the United States Agency for International Development (USAID)/MERC grant no. TA‐MOU‐11‐M31‐025. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government; Israel Science Foundation (ISF) grant no. 877/10; and the Hadassah University Hospital Compensatory Fund. We thank Noemie Cohen for data entry.

Publisher Copyright:
Copyright © 2018 John Wiley & Sons, Ltd.


  • autoimmune disease
  • diffuse large B-cell lymphoma
  • non-Hodgkin lymphoma
  • risk
  • survival


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