Table 3. Clinical and practical (management) implications of CHIP.

Increased risk of development of a myeloid neoplasm –MDS –Acute myeloid leukemia –MPN, including CML –MDS/MPN overlap disorders –Chronic eosinophilic leukemia

Increased potential risk of development of other hematologic neoplasms –Lymphoproliferative neoplasms –Mast cell neoplasms Increased potential risk of development of a cardiovascular event –In otherwise healthy individuals –In patients who have other cardiovascular risk factors –In patients who develop a myeloid neoplasm a –In patients with a myeloid neoplasm after eradication of the dominant clone b –In patients who will undergo SCT c –In patients who receive drugs that may trigger cardiovascular events d

Practical consequences and management issues –Detailed investigation of hematopoietic organs including bone marrow –Delineation from germ line mutations and common gene variants (SNP) –Follow-up examinations (like in low-risk MDS) –Recognition of the evolution to CCUS –Early detection of cardiovascular risk profiles, especially in patients who develop a myeloid neoplasm –Communication issues (how to explain it to the patient) –Need to explore risk profiles in prospective studies –Prophylactic strategies/recommendations (avoidance of additional risk factors) –Computer-based models (to be used by physicians and patients)

CHIP, clonal hematopoiesis with indeterminate potential; SNP, single nucleotide polymorphism; CCUS, clonal hematopoiesis of uncertain significance; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; CML, chronic myeloid leukemia; SCT, stem cell transplantation; SNP, single-nucleotide polymorphism.

^aIn most myeloid neoplasms, the risk of development of a cardiovascular event is higher compared to age-matched healthy controls. Typical examples are JAK2-mutated myelopro-liferative neoplasms and PDGFR-mutated eosinophilic leukemias.

^bEarly molecular subclones exhibiting CHIP mutations but no driver lesions may survive therapy and may thus contribute (still) to the risk of development of a relapse or a cardiovascular event.

^cCertain cardiovascular events, like veno-occlusive disease, may occur during or after SCT.

^dCertain drugs applied in hematology are associated with a higher risk of development of cardiovascular events (e.g., nilotinib, ponatinib, and thalidomide).