Expansion of a Clonal CD8+CD57+ Large Granular Lymphocyte Population After Autologous Stem Cell Transplant in Multiple Myeloma

Abstract

Clonal expansions of large granular lymphocytes (LGLs) have been identified in patients following stem cell transplants and may represent posttransplant LGL leukemias or reactive immune responses. To differentiate between these 2 possibilities, we assessed peripheral blood and bone marrow of patients with myeloma after autologous stem cell transplant. All patients examined shortly after autologous stem cell transplant had significant increases in the LGLs in the peripheral blood and bone marrow (71% of lymphocytes) as compared with controls (39%). This increase was detectable years after transplant. The LGLs had a reproducible immunophenotype of CD8+CD57+ T cells without phenotypic abnormalities in 19 of 20 patients. Sixty-five percent of the post-autologous stem cell transplant patients had clonal T-cell receptor gene rearrangements in the bone marrow, yet no patients had neutropenia or splenomegaly. Although the LGL expansions were clonal and persistent, the lack of clinical sequelae suggests the clonal LGL expansion is a reactive, potentially beneficial, immune response to autologous stem cell transplant.

Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT3 mutations

“…(Chen et al, 2004) Unlike B-cell reconstitution, the absence of a functional thymus precludes post-alloHSCT T-cell recovery to recapitulate the cellular ontogeny. (Mohty et al, 2002;Sabnani et al, 2006;Nann-Rutti et al, 2012;Wolniak et al, 2013). (Weinberg et al, 2001) Persistently elevated numbers of cytotoxic T lymphocytes (CTL) have been shown after autologous and alloHSCT, or following solid organ transplantation, in some cases fulfilling the current diagnostic criteria for large granular lymphocyte (LGL) leukaemia.…”

“…(Mohty et al, 2002;Sabnani et al, 2006;Wolniak et al, 2013) T-LGL leukaemia is defined by a persistent increase of the number of peripheral blood LGL, usually between 2Á0 and 20 9 10 9 /l without a clearly identified cause. Nevertheless, the description of symptomatic LGL leukaemia and aggressive malignant cases in this setting may generate uncertainty, mostly in those cases in which the CTLe persists beyond the early transplantation period.…”

Spectrum of Clonal Large Granular Lymphocytes (LGLs) of αβ T Cells

“…Clinical diseases associated with LGLT clones have been reviewed elsewhere. 5,6,[13][14][15][16][17][18][19][20] For patients with small LGLT clones, we propose the term T-cell clone of undetermined significance, which is slightly different from T-cell clonopathy of undetermined significance, as will be discussed below. The precise size of the clone to distinguish LGLT leukemia from TCUS is not well defined and will likely evolve over time, but we propose a 10-fold increase, which would be an ACC greater than 2.0 × 10 9 /L or %MS greater than 10% for the leukemia.…”

The utility of peripheral blood smear review for identifying specimens for flow cytometric immunophenotyping

“…It's worth emphasizing that borderline T‐cell lymphocytosis is often clonal using flow cytometric and molecular diagnostic studies, but this finding does not equate to neoplasia and likely reflects limited heterogeneity of the immune response . Following allogeneic stem cell, solid organ, and autologous transplant there is often a mild increase in LGL, with a cumulative incidence of 20% at 2 years following transplant . It has been proposed that post‐transplant T‐cell lymphocytosis may be a result of constant antigenic stimulation and/or chronic infection, and demonstrates a strong association chronic GVHD and CMV status.…”