T‐cell clonality testing for the diagnosis of T‐cell large granular lymphocytic leukemia: Are we identifying pathology or incidental clones?

Introduction T‐cell clonality testing by T‐cell receptor (TCR) gene rearrangement is key to the diagnosis of T‐cell lymphoproliferative disorders such as T‐cell large granular lymphocytic (T‐LGL) leukemia. Benign clonal T‐cell expansions, however, are commonly found in patients without identifiable...

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Published in:International journal of laboratory hematology 2022-12, Vol.44 (6), p.1115-1120
Main Authors: Chin‐Yee, Benjamin, Suthakaran, Abitha, Hedley, Benjamin D., Howlett, Christopher, Stuart, Alan, Sadikovic, Bekim, Chin‐Yee, Ian H., Hsia, Cyrus C.
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid - pathology
Clone Cells - pathology
Cloning
Diagnosis
Gene rearrangement
Humans
Immunoproliferative diseases
Leukemia
Leukemia, Large Granular Lymphocytic - diagnosis
Leukemia, Large Granular Lymphocytic - genetics
Leukemia, Large Granular Lymphocytic - pathology
Leukocytes (neutrophilic)
Lymphatic leukemia
Lymphocytes
molecular diagnostics
Patients
Retrospective Studies
Rheumatoid arthritis
T cell receptors
T-Lymphocytes - pathology
T‐cell clonality testing
T‐cell clones of uncertain significance (T‐CUS)
T‐cell large granular lymphocytic (T‐LGL) leukemia
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Summary:Introduction T‐cell clonality testing by T‐cell receptor (TCR) gene rearrangement is key to the diagnosis of T‐cell lymphoproliferative disorders such as T‐cell large granular lymphocytic (T‐LGL) leukemia. Benign clonal T‐cell expansions, however, are commonly found in patients without identifiable disease, a condition referred to as T‐cell clones of uncertain significance (T‐CUS). In practice, T‐cell clonality testing is performed for a range of reasons and results are often challenging to interpret given the overlap between benign and malignant clonal T‐cell proliferations and uncertainties in the management of T‐CUS. Methods We conducted a 5‐year retrospective cohort study of 211 consecutive patients who underwent PCR‐based T‐cell clonality testing for suspected T‐LGL leukemia at our institution to characterize the use of T‐cell clonality testing and its impact on patient management. Results Overall, 46.4% (n = 98) of individuals tested had a clonal T‐cell population identified. Patients with a monoclonal T‐cell population were more likely to be older, have rheumatoid arthritis and have higher lymphocyte counts compared to patients with polyclonal populations. The majority of patients eventually diagnosed and treated for T‐LGL leukemia had rheumatoid arthritis and lower neutrophil counts compared to untreated patients with monoclonal T‐cell populations. A diagnosis of T‐LGL leukemia was made in only a minority of patients (n = 48, 22.7%), and only a small proportion were treated (n = 17, 8.1%). Conclusion Our study suggests that T‐cell clonality testing most commonly identifies incidental T‐cell clones with only a minority of patients receiving a diagnosis of T‐LGL leukemia and fewer requiring active treatment. These finding indicate an opportunity to improve utilization of T‐cell clonality testing in clinical practice to better target patients where the results of testing would impact clinical management.
ISSN:1751-5521
1751-553X
DOI:10.1111/ijlh.13949