Vasculitis Associated with Large Granular Lymphocytes Leukemia

Large granular leukemia (LGL) leukemia is derived from either T-cell or NK-cell lineages. Clinical presentation of LGL leukemia is dominated by recurrent infections associated with neutropenia, anemia, splenomegaly and auto-immune diseases. The association of vasculitis and LGL leukemia has been rarely reported and investigated.

To improve knowledge about this association, we retrospectively describe the clinical and biological characteristics of patients, their response to therapy and their prognosis.

We performed a retrospective study based on 229 patients included in the French national LGL proliferation registry and a national mailing survey to 1350 internists in order to collect medical characteristics of patients displaying both vasculitis and LGL leukemia. We retrospectively collected medical charts from 11 patients between September 1999 and February 2012. Medical history, hematologic laboratory tests and response to therapy were compiled at first presentation of LGL leukemia associated vasculitis (LAV) and at each visit.

At the time of diagnosis of LGL leukemia the mean age was 60. 3 years (range, 28–74 years). They were 9 women and two men. The mean of follow up was 45 months (range, 1–108). The main LGL lineage was T-LGL (10 patients, 91%) and only one NK-LGL was identified. Hematological laboratory findings revealed that 5 patients (45%) patients presented hyperlymphocytosis. The mean absolute circulating LGL count for the series was 1. 10 ⁹/L (range, 0. 45–4. 59 x. 10 ⁹/L). Three patient (27%) had neutropenia (<1. 5 x. 10⁹/L), no one had thrombocytopenia. Anemia was detected in 4 patients (36%). The most frequently observed vasculitis was cryoglobulinemia (n=5). Three patients presented cutaneous vasculitis. Two patients had ANCA negative microscopic polyangiitis and one patient presented giant cell arteritis. Clinical features were dominated by skin localization e. g. purpura (91%), arthralgia (37%), peripheral neuritis (27%) and renal glomerulonephritis (18%). Leucocytoclastic vasculitis was histologically demonstrated in 6 cases. Ten vasculitis were treated: the most delivered treatment was the association of cyclophosphamide-corticosteroid (n=3), followed to methotrexate–corticoisteroid (n=2), chlorambucil-corticosteroid (n=2) and corticosteroid alone (n=2). One patient received azathioprine and corticosteroid. The complete remission rate was high 80% and a minority of them presented vasculitis relapse (27%). Three patients (27%) died: one related to LGL leukemia (acute infection) and the 2 others related to heart failure due to vasculitis.

Association of LGL leukemia and vasculitis is rare but not fortuitous. Based on this retrospective analysis, it seems that LAV preferentially affect female patients, with a low LGL count. LAV present with frequent cutaneous involvement and have a good response to therapy. Pathophysiological link between LGL leukemia and vasculitis remains to be investigated.

No relevant conflicts of interest to declare.