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

Abstract

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 × 109/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.