To the Editor
The recent letter to the Editor by Tiacci and colleagues (Sept. 6 issue)1 sheds light on the need for further subclassification of clonal hematopoiesis of indeterminate potential (CHIP). The authors present a case of a 45-year-old man with CHIP that manifested with rapid development and progression of two hematologic cancers. However, the extent of the hematopoietic subclones and swift progression of the these cancers call into question the classification of this clinical presentation as “CHIP.”
CHIP was first identified through broad sequencing of cell-free DNA in populations that were unselected for hematologic abnormalities, and it has been defined by two characteristics.2,3 First, among patients with CHIP, there is a low absolute risk of transformation from CHIP to hematologic cancer (0.5% to 1.0% per year). Second, CHIP subclones are often present at low levels (median variant allele frequency, 10.0 to 15.0%). In this patient, the extensive subclone burden (which replaced nearly the entire bone marrow) and rapid clinical progression are probably not consistent with the well-characterized definition of CHIP. Research delineating the association of CHIP variants and subclone burden with clinical outcome is lacking.
No potential conflict of interest relevant to this letter was reported.
1. Tiacci E, Venanzi A, Ascani S, et al. High-risk clonal hematopoiesis as the origin of AITL and NPM1-mutated AML. N Engl J Med 2018;379:981–984.
2. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014;371:2488–2498.
3. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014;371:2477–2487.
Enrico Tiacci, M.D.
Brunangelo Falini, M.D.
Perugia University, Perugia, Italy
Since publication of their letter, the authors report no further potential conflict of interest.
1. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014;371:2488–2498.
2. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014;371:2477–2487.
3. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 2018;559:400–404.