Aggressive natural killer cell leukemia in a patient with common variable immunodeficiency syndrome

We wish to update readers about a patient with polyglandular autoimmune syndrome type III accompanied by common variable immunodeficiency, who was published as a case report in this journal [1]. In the second year following diagnosis of common variable immunodeficiency, natural killer (NK) cell acute leukemia developed. She was admitted to our clinic with symptoms of major depression, fatigue, weakness, petechia and ecchymosis. She had hepatomegaly, splenomegaly and enlarged abdominal lymph nodes. In laboratory examination, leukocytosis (leukocyte count 140 000/mm³), anemia (hemoglobin 9 g/dl) and thrombocytopenia (platelet count 40 000/mm³) were detected. In peripheral blood and bone marrow examination, blastic cells resembling large granular lymphocytes accounted for 85% of all cells. Immunophenotype was typically CD2⁺, CD3⁻ and CD56⁺. Allogeneic peripheral blood cell transplantation was performed, but engraftment was not achieved. Two months after transplantation she was admitted to our clinic with findings of relapse. Cytotoxic treatment was not administered due to the dismissal of the patient. Supportive and psychiatric treatment was applied. She is still alive and clinically refractory.

NK cell neoplasms, which include extranodal NK/T-cell lymphoma (nasal and extranasal) and aggressive NK cell leukemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent. A particularly aggressive type of NK malignancy with widespread organ infiltration and a leukemic phase was first described by Fernandez and colleagues [2]. Aggressive NK cell leukemia is a very rare disorder and most reported cases come from Japan and Hong Kong. The disease is mainly observed in Asia and New Zealand. These neoplasms are highly aggressive, and show a strong association with Epstein–Barr virus. Aggressive NK cell leukemia affects younger patients, who present with poor general condition, fever and disseminated disease; they often die within a short time from systemic disease or complications such as multiple organ failure. Peripheral blood and bone marrow show atypical large granular lymphocytes, which exhibit an immunophenotype similar to that of extranodal NK/T-cell lymphoma. Aggressive NK cell leukemia must be distinguished from T-cell large granular lymphocyte leukemia and NK cell lymphoproliferative disorder, both of which are indolent [3],[4].

In addition to frequent infections (sinusitis, bronchitis, pneumonia, otitis, giardiasis), this condition is also associated with an increased risk for developing lymphomas and gastrointestinal malignancies.

We performed a Medline search, but found no report of the coexistence of NK cell leukemia and common variable immunodeficiency in the English literature. The co-occurrence of these two entities may be due to the association of immunodeficiency and malignancy. In this letter, we report this very rare syndrome and its relationship with developing acute NK cell leukemia.