Commentary

Q&A: Clinical implications of clonal hematopoiesis


 

There is growing literature around clonal hematopoiesis (CH) but many questions persist about its clinical significance. On June 14, Hematology News hosted a Twitter question-and-answer session with Aaron Viny, MD , who is on the staff of the leukemia service at Memorial Sloan Kettering Cancer Center in New York and is a member of the Hematology News editorial advisory board, to answer questions about CH and interpret the latest research. The following is an edited version of the Q&A session.

Question: Can you get us started by explaining the difference between clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance?

Dr. Aaron D. Viny is with the Memorial Sloan-Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher.

Dr. Aaron D. Viny

Dr. Viny: So to start, CH is the detection of somatic mutations in the blood or bone marrow of patients without any hematologic disorder – normal counts, no dysplasia, no abnormal cells; whereas clonal cytopenia of undetermined significance is a patient with a detectable somatic mutation, no dysplasia or abnormal cells, but a decrease in hematopoietic output of one or more lineages. It is inferred, but not proven, that the mutation is causing the cytopenia.

Question: So are there differences in CH depending on the gene mutated?

Dr. Viny: Hard to say. The most common mutations found in CH are DNMT3A, TET2, PPM1D, and ASXL1, as shown in the Cell Stem Cell paper by Catherine C. Coombs, MD, and Ross Levine, MD ( 2017 Sep 7;21[3]:374-82.e4 ). So in the setting of patients with acute myeloid leukemia, there are data from several groups showing that persistence of DNMT3A, TET2, and ASXL1 have less recurrence risk, compared with the field. This, of course, does not apply to CH in the absence of a hematologic disorder.

Question: Are you aware of any screening programs for clonal hematopoiesis?

Dr. Viny: Currently at Memorial Sloan Kettering, patients who undergo MSK-IMPACT testing of their solid tumor have a germ line control from blood that is also sequenced. These samples are screened for CH mutations. In fact, there are two recent papers showing one key issue with tumor sequencing and CH: A blood sample is necessary to resolve the compartment of the CH mutation (that is, not in the solid tumor). The papers are JAMA Oncol. 2018 Jun 5. doi: 10.1001/jamaoncol.2018.2297 and Clin Cancer Res. 2018 Jun 4. doi: 10.1158/1078-0432.CCR-18-1201 .

Question: Will patients with CH in screened samples be notified of the results?

Dr. Viny: Yes. The patients are being referred to the Memorial Sloan Kettering clonal hematopoiesis clinic run by Dr. Levine and Kelly Bolton, MD.

Question: Once you screen and detect CH, how should these patients be followed?

Dr. Viny: First, what are the risks these patients face? Extensive work by Siddhartha Jaiswal, MD, PhD, shows that there is an increased risk of cardiovascular disease and an increased risk for leukemia. So with regards to the latter, following with serial complete blood counts seems sufficient, with a bone marrow biopsy at the detection of any cytopenias. With regard to cardiovascular risk, I consider CH akin to an unmodifiable cardiac risk factor. Patients should be counseled to exercise, and depending on any other cardiac risk factors, interventions such as blood pressure control, lipid control, and daily aspirin use should be addressed accordingly.

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