Showing items 1 - 2 of 2

Lessons learned from an unusual presentation of CD3+, CD56- T-Cell large granular lymphocyte leukemia

- Berzins, Stuart, Harrison, Simon, Lee, Robert, Ritz, Nicole, Chan, Andrew, Came, Neil, Curtis, Nigel, Lim, Andrew

  • Authors: Berzins, Stuart , Harrison, Simon , Lee, Robert , Ritz, Nicole , Chan, Andrew , Came, Neil , Curtis, Nigel , Lim, Andrew
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Journal of Clinical Oncology Vol. 28, no. 28 (2010), p. e498- e502
  • Full Text: false
  • Reviewed:
  • Description: The WHO classification subdivides large granular lymphocytic leukemias (LGLLs) into two subtypes, T and natural killer (NK) LGLLs, with distinct immunophenotypes and clinical presentations.1 Although arising from a common progenitor cell, NK cells are bone marrow–derived innate immune cells capable of cytokine production and cytotoxicity, and T cells are thymic-derived, antigen-specific lymphocytes that express a T-cell receptor (TCR).2 Natural killer T (NKT) cells, a subset of T cells, express NK-associated antigens such as CD16, CD56, and CD57, in addition to a CD1d-restricted, semi-invariant TCR.3 The point at which NKT cells branch from other TCR rearranged cells is not clearly defined. However, this is believed to be mediated through CD1d thymic-dependant signaling in CD4 CD8 double-positive thymocyte precursors.4,5 NK LGLL has a CD3−, CD8+, CD16+, CD56+ phenotype, with variable expression of CD57. It presents in teenagers and young adults with “B” symptoms, lymphadenopathy, hepatosplenomegaly, lymphocytosis, anemia, and thrombocytopenia and typically follows an aggressive clinical course.6 T-cell LGLLs are CD3+, CD8+, CD16+ with a clonal TCR rearrangement and defective Fas (CD95) -mediated apoptosis.7,8 Median age of onset is 55 years, presenting with splenomegaly, neutropenia, and recurrent infections. It is associated with rheumatoid arthritis and follows an indolent and protracted clinical course.9 We describe the case of a teenage patient with T-cell LGLL, who despite having a CD56 immunophenotype, initially showed an aggressive clinical course more in keeping with an NKT leukemia. We discuss the reasoning behind his conservative management and the observed changes in lymphocyte count and serum cytokine/chemokine levels over an 18-month period. There have been no reported cases of an initially aggressive presentation with subsequent spontaneous regression.

Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

- Chan, Angela, Neeson, Paul, Leeansyah, Edwin, Tainton, Kellie, Quach, Hang, Prince, Henry, Harrison, Simon, Godfrey, Dale, Ritchie, David, Berzins, Stuart

  • Authors: Chan, Angela , Neeson, Paul , Leeansyah, Edwin , Tainton, Kellie , Quach, Hang , Prince, Henry , Harrison, Simon , Godfrey, Dale , Ritchie, David , Berzins, Stuart
  • Date: 2014
  • Type: Text , Journal article
  • Relation: Clinical and Experimental Immunology Vol. 175, no. 1 (2014), p. 49-58
  • Full Text: false
  • Reviewed:
  • Description: The causes of multiple myeloma (MM) remain obscure and there are few known risk factors; however, natural killer T (NKT) cell abnormalities have been reported in patients with MM, and therapeutic targeting of NKT cells is promoted as a potential treatment. We characterized NKT cell defects in treated and untreated patients with MM and determined the impact of lenalidomide therapy on the NKT cell pool. Lenalidomide is an immunomodulatory drug with co-stimulatory effects on NKT cells in vitro and is an approved treatment for MM, although its mode of action in that context is not well defined. We find that patients with relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast, newly diagnosed patients had relatively normal NKT cell frequency and function prior to treatment, although a specific NKT cell deficiency emerged after high-dose melphalan and autologous stem cell transplantation (ASCT) regimen. This also impacted NK cells and conventional T cells, but the recovery of NKT cells was considerably delayed, resulting in a prolonged, treatment-induced NKT cell deficit. Longitudinal analysis of individual patients revealed that lenalidomide therapy had no in-vivo impact on NKT cell numbers or cytokine production, either as induction therapy, or as maintenance therapy following ASCT, indicating that its clinical benefits in this setting are independent of NKT cell modulation.
  • 1