TY - JOUR
T1 - Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy
AU - Montalban-Bravo, Guillermo
AU - Kanagal-Shamanna, Rashmi
AU - Class, Caleb A.
AU - Sasaki, Koji
AU - Ravandi, Farhad
AU - Cortes, Jorge E.
AU - Daver, Naval
AU - Takahashi, Koichi
AU - Short, Nicholas J.
AU - DiNardo, Courtney D.
AU - Jabbour, Elias
AU - Borthakur, Gautam
AU - Naqvi, Kiran
AU - Issa, Ghayas C.
AU - Konopleva, Marina
AU - Khoury, Joseph D.
AU - Routbort, Mark
AU - Pierce, Sherry
AU - Do, Kim Anh
AU - Bueso-Ramos, Carlos
AU - Patel, Keyur
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
AU - Kadia, Tapan M.
N1 - Funding Information:
This work was supported in part by the University of Texas MD Anderson Cancer Center Support Grant CA016672 (all authors) and the University of Texas MD Anderson MDS/AML Moon Shot (G.M.-B., R.K.-S., C.B.B., C.C., K.T., K.A.S., C.B-R., H.K., and G.G.-M.).
Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous disorder defined by multilineage dysplasia, myelodysplastic syndrome (MDS)-related karyotype, or history of prior MDS. We evaluated 415 patients with AML-MRC treated from 2013 to 2018 and analyzed their clinical outcomes based on the diagnostic criteria of AML-MRC, therapy type and mutation profile. Criteria for AML-MRC included: cytogenetic abnormalities (AML-MRC-C) in 243 (59%), prior history of MDS in 75 (18%) including 47 (11%) with previously untreated MDS (AML-MRC-H) and 28 (7%) with previously treated MDS (AML-MRC-TS), and 97 (23%) with multilineage dysplasia (AML-MRC-M). Median age was 70 years (range 18-94). Among 95 evaluable patients, a total of 37 (39%) had secondary-type (ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) mutations. Mutations in ASXL1, BCOR, SF3B1, SRSF2, and U2AF1 tended to appear in dominant clones. By multivariate analysis, AML-MRC subtype, age and serum LDH levels were independent predictors of outcome, with patients with AML-MRC-M (HR 0.56, CI 0.38-0.84, P =.004) and AML-MRC-H having better OS. Compared to a cohort of 468 patients with AML without MRC, patients with AML-MRC-M/AML-MRC-H had similar outcomes to those with intermediate risk AML by European LeukemiaNet criteria. Intensive therapy was associated with improved OS in patients with AML-MRC-M (HR 0.42, CI 0.19-0.94, P =.036) and with improved EFS in AML-MRC-M and AML-MRC-H (HR 0.26, CI 0.10-0.63, P =.003). This data suggests that not all diagnostic criteria for AML-MRC define high-risk patients and that specific subgroups may benefit from different therapeutic interventions.
AB - Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous disorder defined by multilineage dysplasia, myelodysplastic syndrome (MDS)-related karyotype, or history of prior MDS. We evaluated 415 patients with AML-MRC treated from 2013 to 2018 and analyzed their clinical outcomes based on the diagnostic criteria of AML-MRC, therapy type and mutation profile. Criteria for AML-MRC included: cytogenetic abnormalities (AML-MRC-C) in 243 (59%), prior history of MDS in 75 (18%) including 47 (11%) with previously untreated MDS (AML-MRC-H) and 28 (7%) with previously treated MDS (AML-MRC-TS), and 97 (23%) with multilineage dysplasia (AML-MRC-M). Median age was 70 years (range 18-94). Among 95 evaluable patients, a total of 37 (39%) had secondary-type (ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) mutations. Mutations in ASXL1, BCOR, SF3B1, SRSF2, and U2AF1 tended to appear in dominant clones. By multivariate analysis, AML-MRC subtype, age and serum LDH levels were independent predictors of outcome, with patients with AML-MRC-M (HR 0.56, CI 0.38-0.84, P =.004) and AML-MRC-H having better OS. Compared to a cohort of 468 patients with AML without MRC, patients with AML-MRC-M/AML-MRC-H had similar outcomes to those with intermediate risk AML by European LeukemiaNet criteria. Intensive therapy was associated with improved OS in patients with AML-MRC-M (HR 0.42, CI 0.19-0.94, P =.036) and with improved EFS in AML-MRC-M and AML-MRC-H (HR 0.26, CI 0.10-0.63, P =.003). This data suggests that not all diagnostic criteria for AML-MRC define high-risk patients and that specific subgroups may benefit from different therapeutic interventions.
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U2 - 10.1002/ajh.25769
DO - 10.1002/ajh.25769
M3 - Article
C2 - 32112433
AN - SCOPUS:85082091309
SN - 0361-8609
VL - 95
SP - 612
EP - 622
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 6
ER -