Increased Hematogones Mimic B Lymphoblastic Leukemia in Non-Transplant Bone Marrows of Patients Treated for Acquired Aplastic Anemia
Xiangrong Zhao, Danielle M Townsley, Neal S Young, Irina Maric. NIH, Bethesda, MD
Background: Hematogones are benign B-lymphoid precursors that can masquerade as lymphoblasts of B lymphoblastic leukemia (B-ALL), leading to the false diagnosis of B-ALL. They are usually dispersed singly in bone marrow (BM) without forming aggregates, and decline in number with age. It has been reported that hematogones are reduced in pediatric acquired aplastic anemia (AA), but not described in non-transplant BM of patients treated for acquired AA.
Design: A comprehensive database containing acquired AA cases seen at the Clinical Center, NIH from 2009-2012 was retrospectively searched. All included cases had clinical data and BM findings reviewed and confirmed. Hematogones were identified with an array of immunohistochemical stains covering all B-cell maturation stages (CD34, TdT, CD10, CD79a, CD20), and confirmed by flow cytometry when available. The level over 5% was designated as hematogone increase, and tight aggregation of 5 or more TdT-positive cells in BM biopsies was considered significant.
Results: Eleven BM biopsies had prominent increase in hematogones, forming focal TdT-positive aggregates and sheets of CD10-positive B-lymphoid cells, suspicious for B-ALL. All BMs were hypocellular for age with trilineage hypoplasia. Clustering/sheeting of hematogones was localized to more cellular areas, where recovery of hematopoiesis was also observed. % TdT-positive cells ranged from 5-25%, with a more significant increase in CD10-positive B-cells (up to 50%). Hematogones significantly outnumbered CD3-positive T-cells. All but one were post-treatment BM biopsies for severe AA. All patients received antithymocyte globulin and/or cyclosporine A. There were 5 children and 6 adults (age range 6-66 yrs; median 19 yrs). Median CBC values were: Hgb 9.6, WBC 2.32, neutrophils 1.21, lymphocytes 0.81, and platelets 45. During the follow-up period (median 13 months), none of the patients developed B-ALL. Seven patients had a total of 12 subsequent BM biopsies, none exhibiting persistent increase in hematogones.
Conclusions: For the first time, we report the presence of focally markedly increased, aggregating hematogones in non-transplant BMs of patients treated for acquired AA. Clinical and histopathological follow-up demonstrated the benign, transient nature of this previously undescribed phenomenon. It is known that in AA, erythro-myeloid lineage progenitors must be affected by immune system dysregulation. This current study supports the idea that progenitors of B-lymphoid lineage are also affected, and immunosupression restores hematogone patterns.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 238, Wednesday Morning