What we have learned about lymphocytic variant hypereosinophilic syndrome: A systematic literature review

Lymphocytic variant is a rare subtype of hypereosinophilic syndrome (L-HES) secondary to overproduction of eosinophilopoietic cytokines by the underlying clonal T lymphocytes with abnormal immunophenotypes. Clinical profiles, treatment responses, and outcomes of L-HES are not well characterized given its rarity. We performed a systematic literature review to summarize cases identified in PubMed and Embase databases between January 1994 and July 2021. A total of 148 patients met the inclusion criteria with a median age at diagnosis of 46 years and 51.4% being male. Cutaneous manifestations (81.1%) predominated the clinical picture, while the characteristic cardiovascular involvement was seen in 11.5% of cases. The median eosinophil count at baseline was 5.3 x 10(9)/L and 109 patients (73.6%) had underlying clonal T lymphocytes harboring the classic CD3(-)CD4(+) immunophenotype, which was associated with higher numbers of eosinophils and organ involvement at baseline. Corticosteroids were the most common first-line agent (88.1%), but most patients required additional treatment, leading to clinical or hematologic response in two-thirds. The 10-year overall survival was 81.6% (95% confidence interval [CI] 68.1-89.8). Transformation into malignant T cell lymphoma was observed in 19 patients, specifically in those with cardiovascular involvement (odds ratio [OR] 4.723, 95% CI 1.304-17.108, p = 0.018) and imatinib use (OR 4.284, 95% CI 1.191-15.404, p = 0.026). Taken together, a heavier disease burden was shown in L-HES patients with classic CD3(-)CD4(+ )lymphocytes but they were manageable with corticosteroids and sparing agents. There is an increased risk of lymphoma transformation that could be associated with certain clinical surrogates.

Automated summary

This study provides a comprehensive review of the clinical characteristics, treatment responses, and outcomes of lymphocytic variant hypereosinophilic syndrome (L-HES). The results show that L-HES patients have a heavier disease burden, and the presence of CD3(-)CD4(+) lymphocytes is associated with higher numbers of eosinophils and organ involvement. Corticosteroids are the most commonly used treatment, but additional therapies are often required. In addition, there is an increased risk of lymphoma transformation in L-HES patients, which may be associated with cardiovascular involvement and the use of imatinib.