Immunosequencing Applications in Cutaneous T-Cell Lymphoma

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and disease monitoring in CTCL. The objective of this comprehensive review is to provide a thorough explanation of the application of immunosequencing in the context of CTCL. We describe the significance of T-cell clonality and the methods used to detect it, including a detailed comparison between PCR paired with capillary electrophoresis and HTS-TCR. The utilization of immunosequencing in the blood and skin of CTCL patients is discussed in depth, specifically outlining how HTS-TCR can assist in diagnosing CTCL, predicting outcomes, and tracking disease progression. Finally, we address the potential applications of immunosequencing in clinical management and research as well as the novel challenges it presents

Utility of T-Cell Immunosequencing in Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events

Utility of T-cell immunosequencing in distinguishing mycosis fungoides progression from treatment related cutaneous adverse events

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events

The role of monitoring and evaluation in six South African reading programmes

In this article we focus on six reading programmes and ask: Do these programmes work insofar as they improve the reading ability of programme participants? We apply programme evaluation methods and content to these programmes to answer this question. Specifically, we use an approach that identifies the following five different levels of evaluation, namely: programme need; programme theory; programme process and implementation; programme outcome and impact; and programme cost and efficiency. We then add appropriate evaluation questions and research designs applicable to each level. We conclude by providing suggestions to reading programme staff on how to improve monitoring (data collection) in order to strengthen the evaluability of their reading programmes