Frequent Coincident Clonal Hematopoietic Expansions In Patients with Hairy Cell Leukemia

Abstract 2428

Hairy cell leukemia is usually an indolent clonal proliferation of mature B cells involving blood, bone marrow, and spleen and is often characterized by progressive cytopenias. Patients with HCL have been observed to be at increased risk for a subset non-hematopoietic and hematopoietic neoplasms in some, but not all epidemiologic studies. The reason for such an increase is not entirely clear and has been postulated to be either due to immunosuppressive therapy that is used to treat HCL, an immunosuppressive effect of HCL itself, and/or to the intrinsic cancer susceptibility of the HCL patients. The finding of an increased cancer burden of HCL patients at diagnosis and lack of consistent association with any specific therapy is somewhat supportive of the last explanation. Aside from the epidemiologic studies, reports of second hematologic malignancies in patients with HCL are mostly contained in case reports and series containing very few HCL patients. To our knowledge no large systematic studies of additional clonal hematopoietic proliferations that can be detected in routine clinical specimen in patients with hairy cell leukemia have been performed.

We identified 115 patients with hairy cell leukemia documented by flow cytometry in our institution between the years of 2004 and 2010. To qualify for the study the case had to have a clonal mature B cell population with expression of the canonical hairy cell leukemia antigens CD25, CD11c and CD103 on a population with increased side scatter. Immunophenotypic variants lacking one or more of these antigens were excluded to avoid sample contamination with HCL-variant and marginal zone lymphoma. Whenever possible correlation with clinical and morphologic evaluation was also performed. Of those patients 12 (10.4%) had one or more additional clonal hematopoietic proliferations identified either at diagnosis or in a subsequent sample. 7/12 patients had both neoplastic proliferations present at the time of diagnosis while the remaining 5 patients developed the second neoplasm after an established history of hairy cell leukemia. Compared to patients without additional neoplasms, the patients with additional clonal populations were older (average age 66 (47–85) vs. 56 (27–95) year old, p<0.01, two tailed t test). Compared to younger patients, HCL patients over age 60 had a significantly increased probability of having a second hematopoietic neoplasm (20% vs. 5.3%, OR 3.8, p<0.001, two tailed Chi-squared test). The majority 8/12 had another B cell neoplasm while the remainder had evidence of a plasma cell neoplasm. Two patients had coincident chronic lymphocytic leukemia (CLL) with an additional five patients presenting with a monoclonal B lymphocytosis (MBL) having a CLL like immunophenotype. One patient developed mantle cell lymphoma. One patient had three additional neoplastic populations which included a clonal B cell population negative for CD5, CD10, CD11c, or CD103, most consistent with either a marginal zone lymphoma or a lymphoplasmacytic lymphoma, a small clonal plasma cell population suggestive of monoclonal gammopathy of undetermined significance, and an MBL population with a CLL like immunophenotype. Five patients had a plasma cell neoplasm (three with clinical diagnosis of multiple myeloma). We have also identified a clear case of bi-clonal hairy cell leukemia that to our knowledge has only been reported once in the literature and never using contemporary diagnostic criteria. Our study demonstrates that additional clonal hematopoietic proliferations associated with HCL are common. Increased vigilance for coincident hematopoietic neoplasms may be warranted particularly in older patients with this disease.