Neutropenia Etiology Influences Resulting Hematologic Consequences

Hematological consequences of severe chronic neutropenia vary based on the underlying etiology of the condition, according to a study abstract presented at the 60th American Society of Hematology Annual Meeting & Exposition.

Drawing on data from the Severe Chronic Neutropenia International Registry, the researchers identified 1672 patients with chronic neutropenia. Since 1994, the registry has enrolled children and adults with more than 3 absolute neutrophil counts of less than 0.5×10⁹/L over a 3-month period, resulting in 17,577 person-years of data over the last 15 years. Demographic, clinical, and laboratory data were collected from all patients.

The registry includes patients in 3 categories, including congenital patients (38%) with mutations in ELANE, SBDS, TAZ, COH1, CXCR4, SLC37A4, G6PC3, WAS, CSF3R, SRP54, GFI1, VPS45, JAGN1, HAX1, as well as patients with severe neutropenia since early childhood without a genetic diagnosis. The registry also includes cyclic patients (15%) with oscillations in their absolute neutrophil count and idiopathic/autoimmune patients (47%), which include children and adults with large granular lymphocytes syndrome without recognized features of a lymphoproliferative disorder.

Over the study period, 70 patients developed myelodysplasia or acute myeloid leukemia (AML), 99% of whom have been diagnosed with a hereditary type of neutropenia, including severe congenital neutropenia (n = 55), glycogen storage disease 1b (n = 3), congenital immunodeficiency (n = 2), Shwachman-Diamond syndrome (n = 5), WHIM syndrome (n = 1), Wiskott-Aldrich syndrome (n = 2), cyclic neutropenia (n = 1), and idiopathic neutropenia (n = 1).

Four congenital patients and 1 idiopathic patient developed myelofibrosis, and 2 congenital patients later developed AML. According to the researchers, most patients in the registry have been treated with granulocyte colony-stimulating factor, and the treatment was associated with a favorable prognosis.

Meanwhile, 12 patients developed T-cell lymphoproliferative disorder (1 autoimmune neutropenia, 3 congenital neutropenia, and 8 idiopathic neutropenia), and 10 patients have reported other hematological malignancies, including chronic myeloid leukemia, chronic lymphocytic leukemia, and lymphoma.

“The diagnosis of cyclic neutropenia and chronic idiopathic/autoimmune neutropenia portends a favorable prognosis, based on a total of 10,482 person years of observation,” wrote the researchers.

Although outcomes for patients with myelodysplasia and AML who received chemotherapy with hematopoietic stem cell transplantation were poor before 2000, with just 18% surviving, survival significantly increased after 2000, with 66% surviving.

Reference

Dale D, Bolyard A, Alter B, et al. Myelodysplasia, leukemia, lymphoid malignancies,and other cancers in patients with severe chronic neutropenia. Presented at: 60th American Society of Hematology Annual Meeting & Exposition; December 1, 2018; San Diego, CA. Abstract 16.