Angioimmunoblastic T-Cell Lymphoma

Angioimmunoblastic T-cell lymphoma is a follicular T-helper–derived neoplasm displaying a peculiar morphologic appearance and biological complexity. New mutations have been described that contribute to elucidating the underlying pathogenetic events. The disease behaves aggressively and typically affects elderly patients. The outcomes reported with anthracycline-containing regimens are poor; therefore autologous transplantation in first remission should be offered whenever possible. Newer approaches are urgently needed for relapsed and refractory patients. Newly approved agents show activity in pretreated patients but response durations are short. Innovative induction strategies (CHOP + biologic agent) should be designed to enhance response quality, facilitate transplantation, and prolong survival.

Key points

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Angioimmunoblastic T-cell lymphoma is a follicular T-helper–derived neoplasm, sharing many of its features with a proportion of peripheral T-cell lymphomas, not otherwise specified.
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New mutations have been recently described ( TET2 , DNMT3A , IDH2 , RHOA ), and fresh biological insights into the molecular pathogenesis of the disease are now available.
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Anthracycline-containing regimens represent the most widely adopted first-line option, to be followed by a consolidative autologous transplantation whenever possible.
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Newly approved agents and off-label compounds (romidepsin, belinostat, brentuximab vedotin, lenalidomide) seem active in pretreated patients but response durations are short.
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Innovative induction strategies (CHOP + biologic agent) should be designed to enhance response quality, facilitate autoSCT and prolong survival.

Introduction and epidemiology

An angioimmunoblastic lymphadenopathy with dysproteinemia was first described by the group of Henry Rappaport in the 1970s. At that time, it was not recognized as a malignant condition because some patients seemed to gain long-term benefit from steroid treatment. Some investigators reported, however, that this condition was prone to progression to an overt lymphoma, and underscored the difficulty of pathologists in establishing a clear-cut distinction between a “benign” and a “malignant” lesion based on morphology alone. Angioimmunoblastic T-cell lymphoma (AITL) is an acknowledged entity since the 1994 Revised European American Lymphoma (REAL) Classification. Given that a number of recurrent mutations and a peculiar gene signature characterize a significant proportion of AITL cases (see next paragraph for details), as well as some cases of peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS), which manifest a follicular T-helper (T _FH) phenotype, the 2016 revision of the World Health Organization classification unifies under a common heading AITL, follicular T-cell lymphoma, and nodal PTCL with T _FHphenotype.

AITL is a rare disease, which accounts for only 1% to 2% of non-Hodgkin lymphomas and 15% to 20% of PTCL. Incidence is low, with 0.05 new cases diagnosed per 100,000 patients in the United States per year. Disease incidence is higher in Europe (29% of all cases of PTCL), followed by Asia (18%) and North America (16%): the reasons for this heterogeneity in different parts of the world are unexplained. AITL is generally regarded as the second most common PTCL entity, although it was the prevalent subtype in 2 recently published French datasets, in which it represented 36.1% of all PTCL cases. This may be explained by a geographic heterogeneity of incidence across Europe, but more likely reflects a refined classification of PTCL-NOS cases by the use of novel molecular tools in more recent studies.

The purpose of this article is to provide a brief overview of the new biological insights of AITL, to discuss patients’ management, and to review the currently adopted treatment strategies for newly diagnosed, relapsed, and refractory disease.

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