TY - JOUR
T1 - MDS-508 Contemporary Evaluation of a Cohort of Patients With Clonal Hematopoiesis (CH)
T2 - A Single Institution Experience
AU - Ong, Faustine
AU - Kim, Kunhwa
AU - Shamanna, Rashmi Kanagal
AU - DiNardo, Courtney
AU - Takahashi, Koichi
AU - Kadia, Tapan
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Hammond, Danielle
AU - Pemmaraju, Naveen
AU - Pierce, Sherry A.
AU - Bravo, Guillermo Montalban
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
AU - Chien, Kelly S.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - Context: Therapy-related CH and the effect of concomitant malignancies hasn't been fully characterized. Design: We conducted a retrospective review of 78 CH patients from a single tertiary cancer center (2015-2021). Patients were categorized into 4 groups: CH of indeterminate potential (CHIP) on active primary cancer treatment (CHIP/T, n=6), other CHIP (CHIP/N, n=26), clonal cytopenia of undetermined significance (CCUS) on concurrent primary cancer therapy or with active malignancies (CCUS/T, n=13), and other CCUS (CCUS/N, n=26). Results: Median age at CH diagnosis was 72 in all patients, whereas median age of CHIP/T was younger at 66. Majority of study patients had another cancer diagnosis (76%) or cardiovascular comorbidities (73%). Most baseline characteristics were comparable, but more CHIP patients had normal cytogenetics. The most common mutations were DNMT3A (40%), TET2 (31%), TP53 (26%), and ASXL1 (18%). Median variant allelic frequency was 7.8%. TP53 mutations were more frequently seen in CCUS. All patients with CHIP were observed, and some CCUS/N (49%) and CCUS/T (31%) received CH-directed therapy, including growth factors, immunoglobulin, cyclosporine, rituximab, and corticosteroids. Twelve patients transformed to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with a median time to transformation of 6.8 months since CH diagnosis. Transformation occurred in 21% CCUS/T, 17% CHIP/T, 15% CCUS/N, and 4% CHIP/N. Median overall survival (OS) after transformation was not reached, with a 2-year OS of 64%. CCUS/T had inferior survival with median OS of 32 months, whereas median OS of all 3 other groups was not reached. There were no significant differences in OS by transformation status, comorbidities, TP53 mutations, or previous treatment history. The most common causes of death were primary malignancy (35%) and comorbidities or transformation to MDS/AML (20% each). Conclusions: This is a tertiary cancer center CH experience with 76% having another malignancy. Median time to transformation to MDS/AML was short at 6.8 months, but patients had a favorable outcome with 2-year OS at 64% and only 20% CH-related deaths. CCUS/T had a higher rate of transformation to myeloid neoplasms at 21% with inferior survival, warranting possible therapeutic interventions in these high-risk patients in the future.
AB - Context: Therapy-related CH and the effect of concomitant malignancies hasn't been fully characterized. Design: We conducted a retrospective review of 78 CH patients from a single tertiary cancer center (2015-2021). Patients were categorized into 4 groups: CH of indeterminate potential (CHIP) on active primary cancer treatment (CHIP/T, n=6), other CHIP (CHIP/N, n=26), clonal cytopenia of undetermined significance (CCUS) on concurrent primary cancer therapy or with active malignancies (CCUS/T, n=13), and other CCUS (CCUS/N, n=26). Results: Median age at CH diagnosis was 72 in all patients, whereas median age of CHIP/T was younger at 66. Majority of study patients had another cancer diagnosis (76%) or cardiovascular comorbidities (73%). Most baseline characteristics were comparable, but more CHIP patients had normal cytogenetics. The most common mutations were DNMT3A (40%), TET2 (31%), TP53 (26%), and ASXL1 (18%). Median variant allelic frequency was 7.8%. TP53 mutations were more frequently seen in CCUS. All patients with CHIP were observed, and some CCUS/N (49%) and CCUS/T (31%) received CH-directed therapy, including growth factors, immunoglobulin, cyclosporine, rituximab, and corticosteroids. Twelve patients transformed to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with a median time to transformation of 6.8 months since CH diagnosis. Transformation occurred in 21% CCUS/T, 17% CHIP/T, 15% CCUS/N, and 4% CHIP/N. Median overall survival (OS) after transformation was not reached, with a 2-year OS of 64%. CCUS/T had inferior survival with median OS of 32 months, whereas median OS of all 3 other groups was not reached. There were no significant differences in OS by transformation status, comorbidities, TP53 mutations, or previous treatment history. The most common causes of death were primary malignancy (35%) and comorbidities or transformation to MDS/AML (20% each). Conclusions: This is a tertiary cancer center CH experience with 76% having another malignancy. Median time to transformation to MDS/AML was short at 6.8 months, but patients had a favorable outcome with 2-year OS at 64% and only 20% CH-related deaths. CCUS/T had a higher rate of transformation to myeloid neoplasms at 21% with inferior survival, warranting possible therapeutic interventions in these high-risk patients in the future.
KW - acute myeloid leukemia
KW - clonal hematopoiesis
KW - MDS
KW - myelodysplastic syndrome
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U2 - 10.1016/S2152-2650(22)01424-0
DO - 10.1016/S2152-2650(22)01424-0
M3 - Article
C2 - 36163972
AN - SCOPUS:85138173728
SN - 2152-2650
VL - 22
SP - S319
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -