TY - JOUR
T1 - Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia
AU - Short, Nicholas J.
AU - Patel, Keyur P.
AU - Albitar, Maher
AU - Franquiz, Miguel
AU - Luthra, Rajyalakshmi
AU - Kanagal-Shamanna, Rashmi
AU - Wang, Feng
AU - Assi, Rita
AU - Montalban-Bravo, Guillermo
AU - Matthews, Jairo
AU - Ma, Wanlong
AU - Loghavi, Sanam
AU - Takahashi, Koichi
AU - Issa, Ghayas C.
AU - Kornblau, Steven M.
AU - Jabbour, Elias
AU - Garcia-Manero, Guillermo
AU - Kantarjian, Hagop M.
AU - Estrov, Zeev
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/4/28
Y1 - 2020/4/28
N2 - Circulating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing of ccfDNA and bone marrow at the time of diagnosis and after achieving remission in 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total of 39 unique somatic mutations were detected. Five mutations (13%) were detected only in ccfDNA, and 15 (38%) were detected only in bone marrow. Among the 19 mutations detected in both sources, the concordance of variant allelic frequency (VAF) assessment by both methods was high (R2 5 0.849). Mutations detected in only 1 source generally had lower VAF than those detected in both sources, suggesting that either method may miss small subclonal populations. In 3 patients, sequencing of ccfDNA detected new or persistent leukemia-associated mutations during remission that appeared to herald overt relapse. Overall, this study demonstrates that sequencing of ccfDNA in patients with AML can identify clinically relevant mutations not detected in the bone marrow and may play a role in the assessment of measurable residual disease. However, mutations were missed by both ccfDNA and bone marrow analyses, particularly when the VAF was,10%, suggesting that ccfDNA and bone marrow may be complementary in the assessment and monitoring of patients with AML.
AB - Circulating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing of ccfDNA and bone marrow at the time of diagnosis and after achieving remission in 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total of 39 unique somatic mutations were detected. Five mutations (13%) were detected only in ccfDNA, and 15 (38%) were detected only in bone marrow. Among the 19 mutations detected in both sources, the concordance of variant allelic frequency (VAF) assessment by both methods was high (R2 5 0.849). Mutations detected in only 1 source generally had lower VAF than those detected in both sources, suggesting that either method may miss small subclonal populations. In 3 patients, sequencing of ccfDNA detected new or persistent leukemia-associated mutations during remission that appeared to herald overt relapse. Overall, this study demonstrates that sequencing of ccfDNA in patients with AML can identify clinically relevant mutations not detected in the bone marrow and may play a role in the assessment of measurable residual disease. However, mutations were missed by both ccfDNA and bone marrow analyses, particularly when the VAF was,10%, suggesting that ccfDNA and bone marrow may be complementary in the assessment and monitoring of patients with AML.
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U2 - 10.1182/bloodadvances.2019001156
DO - 10.1182/bloodadvances.2019001156
M3 - Article
C2 - 32324887
AN - SCOPUS:85084156416
SN - 2473-9529
VL - 4
SP - 1670
EP - 1677
JO - Blood Advances
JF - Blood Advances
IS - 8
ER -