The Severe Chronic Neutropenia International Registry (the Registry) opened in 1994 to study the long-term safety and efficacy of granulocyte-colony stimulating factor (G-CSF) treatment for patients with congenital, cyclic, and idiopathic neutropenia. The Registry initially evaluated hematological parameters, growth and development, consequence of pregnancy, and other important clinical events. Through the Registry we have learned that patients with congenital neutropenia on long-term G-CSF have a risk of evolution to leukemia of approximately two percent per year. Then, through development of a repository of biological materials, linkage analysis, DNA sequencing, and cellular studies, we have learned that both cyclic and most cases of congenital neutropenia are attributable to mutations in the gene encoding neutrophil elastase. We have also learned that mutations in the receptor for G-CSF frequently occur in the course of evolution of congenital neutropenia to acute myelogenous leukemia. We have also collaborated with other research groups studying candidate genes as causes for neutropenia. The Registry currently includes more than 1300 patients and the Repository contains more than 650 samples from patients, normal relatives, and normal volunteers. The Registry is now an international research organization based at the University of Washington. In this application, we request funding to continue the work of the Registry.
The specific aims are: (1) To continue to enroll and follow patients through carefully longitudinal studies, emphasizing increasing diversity of racial, age, and ethnic backgrounds; (2) To expand a bank of biological materials, to support genetic and molecular research, and to study the evolution of patients to myelodysplasia and leukemia and; (3) To enhance our efforts to disseminate information on the causes, consequences, and treatments of diseases causing severe chronic neutropenia. All of these efforts are directed toward improving understanding in the care of patients with severe neutropenia.
| Dale, David C (2018) Editorial: myeloid biology issue 2018. Curr Opin Hematol 25:1-2 |
| Dale, David C; Crawford, Jeffrey; Klippel, Zandra et al. (2018) A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Support Care Cancer 26:7-20 |
| Xia, Jun; Miller, Christopher A; Baty, Jack et al. (2018) Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood 131:408-416 |
| Makaryan, Vahagn; Kelley, Merideth L; Fletcher, Breanna et al. (2017) Elastase inhibitors as potential therapies for ELANE-associated neutropenia. J Leukoc Biol 102:1143-1151 |
| Skokowa, Julia; Dale, David C; Touw, Ivo P et al. (2017) Severe congenital neutropenias. Nat Rev Dis Primers 3:17032 |
| Dale, David C (2017) How I manage children with neutropenia. Br J Haematol 178:351-363 |
| Dale, David C (2017) Editorial for myeloid biology 2017. Curr Opin Hematol 24:1-2 |
| Dale, David C; Bolyard, AudreyAnna; Marrero, Tracy et al. (2017) Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia. N Engl J Med 377:2290-2292 |
| Dale, David C; Bolyard, Audrey A (2017) An update on the diagnosis and treatment of chronic idiopathic neutropenia. Curr Opin Hematol 24:46-53 |
| Dale, David C (2016) Editorial: The mysteries of the spleen. J Leukoc Biol 100:249-51 |
Showing the most recent 10 out of 52 publications
