Emergence of Bruton's tyrosine kinase-negative Hodgkin lymphoma during ibrutinib treatment of chronic lymphocytic leukaemia

Eur J Haematol. 2017 Oct;99(4):378-380. doi: 10.1111/ejh.12911. Epub 2017 Jul 5.

Abstract

Chronic lymphocytic leukaemia (CLL) is a chronic B-cell lympho-proliferative disorder in which lymphomatous transformations occur in 5%-15% of patients. Histologically these cases resemble diffuse large B-cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67-year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers. Bone marrow trephine, and lymph node biopsy revealed classical HL with negative immuno-histochemistry for Btk in HL cells, on a backdrop of CLL. The patient commenced treatment with Adriamycin, Vinblastine and Dacarbazine (AVD), which resulted in an excellent response. Hodgkin transformation of CLL is rare with a single retrospective study of 4121 CLL patients reporting only 18 cases. Btk expression in HL cells is recently recognised in classical HL; however, the majority of HLs are Btk negative. Given that Btk inhibitors have recently been shown to induce genomic instability in B cells, in the context of their widespread use, such emerging cases are increasingly relevant.

Keywords: Hodgkin lymphoma; chronic lymphocytic leukaemia.

Publication types

  • Case Reports

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biopsy
  • Bone Marrow / pathology
  • Fatal Outcome
  • Female
  • Hodgkin Disease / diagnosis*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / etiology*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Neoplasms, Second Primary / diagnosis*
  • Neoplasms, Second Primary / etiology*
  • Piperidines
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*

Substances

  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine