Characteristics and clinical outcomes of patients with acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
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
Affiliations
Guillaume Richard-Carpentier
Department of Medicine, Division of Medical Oncology and Hematology, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Caitlin R. Rausch
Division of Pharmacy, University of Texas, MD Anderson Cancer Center, Houston, Texas
Koji Sasaki
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Danielle Hammond
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Kiyomi Morita
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Koichi Takahashi
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Guilin Tang
Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Rashmi Kanagal-Shamanna
Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Kapil Bhalla
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Courtney D. Dinardo
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Gautam Borthakur
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Naveen Pemmaraju
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Elizabeth J. Shpall
Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Amin Alousi
Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Naval G. Daver
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Guillermo Garcia-Manero
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Marina Y. Konopleva
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Farhad Ravandi
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Hagop M. Kantarjian
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
Tapan M. Kadia
Department of Leukemia, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas
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.