Characteristics and Clinical Outcomes of Patients With Acute Myeloid Leukemia With inv(3)(q21q26.2) or t(3; 3)(q21; q26.2)

Authors

Guillaume Richard-Carpentier
Caitlin R Rausch
Koji Sasaki
Danielle Hammond
Kiyomi Morita
Koichi Takahashi
Guilin Tang
Rashmi Kanagal-Shamanna
Kapil Bhalla
Courtney D Dinardo
Gautam Borthakur
Naveen Pemmaraju
Elizabeth J Shpall
Amin Alousi
Naval G Daver
Guillermo Garcia-Manero
Marina Y Konopleva
Farhad Ravandi
Hagop M Kantarjian
Tapan M Kadia

Publication Date

9-1-2023

Journal

Haematologica

Abstract

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission (CRc) rate was 46% overall; 46% with high-intensity treatments and 47% with lowintensity treatments. The 30-day mortality was 14% and 0%, with high- and low-intensity treatment, respectively. In R/R patients, the CRc rate was 14%. Venetoclax based-regimens were associated with a CRc rate of 33%. The 3-year overall survival (OS) was 8.8% and 7.1% in ND and R/R patients, respectively. The 3-year cumulative incidence of relapse was 81.7% overall. Older age, high WBC, high peripheral blast count, secondary AML and KRAS, ASXL1, DNMT3A mutations were associated with worse OS in univariable analyses. The 5-year OS rates were 44% and 6% with or without hematopoietic stem cell transplantation in CR1, respectively. AML with inv(3)/t(3;3) is associated with low CR rates, very high risk of relapse and dismal long-term survival. Intensive chemotherapy and hy pomethylating agents provide similar rates of remission and patients achieving CR benefit from hematopoietic stem cell transplantation in first CR.

Keywords

Humans, Middle Aged, Retrospective Studies, Proto-Oncogene Proteins p21(ras), Translocation, Genetic, Chromosome Inversion, Leukemia, Myeloid, Acute, Transcription Factors, Prognosis

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Associated Data

PMID: 36951163