Large granular lymphocytic leukaemia after solid organ and haematopoietic stem cell transplantation

Abstract

Summary T‐cell large granular lymphocytic leukaemia (T‐LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T‐LGLL seen at our institution over the last 10 years, we encountered 15 cases following solid organ or haematopoietic stem cell transplantation. Here, we studied the clinical characterization of these cases and compared them to de novo T‐LGLL. This experience represented a clear picture of the intricate nature of the disease manifestation and the complexities of several immune mechanisms triggering the clonal expansion.

Persistent Large Granular Lymphocyte Clonal Expansions: “The Root of Many Evils”—And of Some Goodness

“…The exact prevalence of LGLL in solid organ transplant recipients remains unknown [ 158 ]. Most of the available evidence derives from case reports [ 159 , 160 , 161 , 162 ] and case series [ 163 ]. The first article informing about this association was published in 1995 [ 159 ] Feher et al described a T-LGLL in a patient following liver transplantation.…”

“…PRCA and AIHA have been rarely communicated [ 160 , 162 , 164 ]. In a work conducted by Awada et al in 2020, STAT3 mutations were identified in 2/13 (15%) patients with LGLL after solid organ transplantation [ 163 ].…”

“…They found that cytopenias were more frequent among de novo T-LGLL patients, while post-transplantation T-LGLL cases showed higher lymphocyte counts. Interestingly, 2/13 (15%) patients with post-transplantation T-LGLL had acquired a STAT3 mutation, as noted above, and in both cases after solid organ transplantation [ 163 ]. As far as we know, no donor-derived LGL expansion after alloHSCT has been reported to carry a STAT3 somatic mutation.…”

The Value of Flow Cytometry Clonality in Large Granular Lymphocyte Leukemia

“…From selected articles ( n = 20), data were collected into a standardized form including publication year, source, number of total patients and divided by sex, number of subjects with autoimmune disorders, hematological malignancies, or cancers, and Vβ usage by flow cytometry ( Table 2 ) [ 41 , 42 , 46 , 75 , 76 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. A total of 533 T-LGL leukemia patients were evaluable for Vβ usage analysis, and sex was available in 524 subjects: 308 of them were males (58.8%) and 216 females (41.2%) with a male:female ratio of 1.4, as already described in smaller cohorts [ 1 ].…”

“…Studies were included when: (1) the year of publication was between 2011 and 2021; (2) the studies were conducted on humans and reported clinical data and Vβ usage by flow cytometry; and (3) the studies were on T-LGL leukemia (Figure 2). From selected articles (n = 20), data were collected into a standardized form including publication year, source, number of total patients and divided by sex, number of subjects with autoimmune disorders, hematological malignancies, or cancers, and Vβ usage by flow cytometry (Table 2) [41,42,46,75,76,[88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107]. A total of 533 T-LGL leukemia patients were evaluable for Vβ usage analysis, and sex was available in 524 subjects: 308 of them were males (58.8%) and 216 females (41.2%) with a male:female ratio of 1.4, as already described in smaller cohorts [1].…”