Skewing of the T-cell receptor repertoire in patients receiving rituximab after allogeneic hematopoietic cell transplantation: what lies beneath?

Leuk Lymphoma. 2019 Jul;60(7):1685-1692. doi: 10.1080/10428194.2018.1543881. Epub 2019 Jan 17.


Rituximab is known to affect T cell immune responses. We and others have reported expansions of T large granular lymphocytes (T-LGLs) in lymphoma patients after Rituximab. We report here the immunogenetic profiling of the T cell receptor (TR) gene repertoire in 14 patients who received Rituximab post allo-HCT and explore clinicobiological correlations. All experienced antigenic triggers, CMV, EBV re-activation and chronic GvHD and had been treated with Rituximab. Skewing of TRBV genes was observed: 3 TRBV genes accounted for half of the repertoire. Oligoclonal pattern with expanded clonotypes was common. Patients with oligoclonality exhibited frequently cGvHD. Longitudinal samples in one revealed distinct clonotypes, suggesting clonal drift. T-LGL leukemia of donor origin with mixed chimerism eventually developed. In conclusion, we report development of oligoclonal T-LGLs after Rituximab post allo-HCT, alluding to antigen selection. Persistence of this phenomenon likely reflects strong antigenic stimulation by viruses and/or cGVHD aggravated by Rituximab.

Keywords: Rituximab; T LGL leukemia; allo-HCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Immunological / adverse effects
  • Clonal Evolution*
  • Female
  • Follow-Up Studies
  • Gene Rearrangement, T-Lymphocyte / genetics
  • Gene Rearrangement, T-Lymphocyte / immunology*
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / pathology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Leukemia, Large Granular Lymphocytic / chemically induced
  • Leukemia, Large Granular Lymphocytic / immunology
  • Leukemia, Large Granular Lymphocytic / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Retrospective Studies
  • Rituximab / adverse effects*
  • Survival Rate
  • Transplantation, Homologous
  • Virus Activation / drug effects
  • Young Adult


  • Antineoplastic Agents, Immunological
  • Receptors, Antigen, T-Cell, alpha-beta
  • Rituximab