TY - JOUR
T1 - A dynamic 3-factor survival model for acute myeloid leukemia that accounts for response to induction chemotherapy
AU - Tefferi, Ayalew
AU - Gangat, Naseema
AU - Al-Kali, Aref
AU - Alkhateeb, Hassan
AU - Shah, Mithun
AU - Patnaik, Mrinal S.
AU - Elliott, Michelle A.
AU - Hogan, William J.
AU - Litzow, Mark R.
AU - Hook, Christopher C.
AU - Mangaonkar, Abhishek
AU - Viswanatha, David
AU - Chen, Dong
AU - Pardanani, Animesh
AU - Ketterling, Rhett P.
AU - DiNardo, Courtney D.
AU - Kadia, Tapan M.
AU - Ravandi, Farhad
AU - Sasaki, Koji
AU - Begna, Kebede H.
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/9
Y1 - 2022/9
N2 - The current study was approached with the assumption that response to induction chemotherapy, in acute myeloid leukemia (AML), overshadows pre-treatment risk variables in predicting survival and therefore be used as an anchor for a simplified risk model. We considered 759 intensively-treated patients with AML, not promyelocytic: median age 60 years; primary 66%, secondary 25%, and therapy-related 9%; European LeukemiaNet cytogenetic risk category favorable 8%, intermediate 61%, and adverse 31%. Complete remission with (CR) or without (CRi) count recovery was achieved in 608 (80%) patients. After a median follow-up of 22 months, 503 deaths, 272 relapses, and 257 allogeneic hematopoietic stem cell transplants (AHSCTs) were recorded. Multivariable analysis identified failure to achieve CR/CRi (HR 3.8, 95% CI 3.1–4.8), adverse karyotype (2.2, 1.8–2.8), and age >55 years (2.1, 1.6–2.7) as main risk factors for survival. HR-weighted scoring resulted in four-tiered risk stratification: low (0 points; N = 183), intermediate-1 (1 point; N = 331), intermediate-2 (2 points; N = 117), and high (≥3 points; N = 128), with respective median survival (5-year rate) not reached (68%), 34 (37%), 13 (20%), and 5 (5%) months (p <.001). FLT3-ITD mutation was associated with inferior survival in intermediate-1 (p =.004) and TP53 in intermediate-2 (p =.06) and high (p =.02) risk disease; the latter was fully accounted for by the close association between TP53 mutation and complex/monosomal karyotype while the observations regarding FLT3-ITD were not affected by treatment with midostaurin. AHSCT had a favorable impact on survival, most apparent in intermediate-1 (p <.001), intermediate-2 (p =.03), and high (p =.01) risk disease. The proposed 3-factor survival model offers a novel prototype that is amenable to further enhancement by molecular information and was validated in an external cohort of 1032 intensively-treated AML patients.
AB - The current study was approached with the assumption that response to induction chemotherapy, in acute myeloid leukemia (AML), overshadows pre-treatment risk variables in predicting survival and therefore be used as an anchor for a simplified risk model. We considered 759 intensively-treated patients with AML, not promyelocytic: median age 60 years; primary 66%, secondary 25%, and therapy-related 9%; European LeukemiaNet cytogenetic risk category favorable 8%, intermediate 61%, and adverse 31%. Complete remission with (CR) or without (CRi) count recovery was achieved in 608 (80%) patients. After a median follow-up of 22 months, 503 deaths, 272 relapses, and 257 allogeneic hematopoietic stem cell transplants (AHSCTs) were recorded. Multivariable analysis identified failure to achieve CR/CRi (HR 3.8, 95% CI 3.1–4.8), adverse karyotype (2.2, 1.8–2.8), and age >55 years (2.1, 1.6–2.7) as main risk factors for survival. HR-weighted scoring resulted in four-tiered risk stratification: low (0 points; N = 183), intermediate-1 (1 point; N = 331), intermediate-2 (2 points; N = 117), and high (≥3 points; N = 128), with respective median survival (5-year rate) not reached (68%), 34 (37%), 13 (20%), and 5 (5%) months (p <.001). FLT3-ITD mutation was associated with inferior survival in intermediate-1 (p =.004) and TP53 in intermediate-2 (p =.06) and high (p =.02) risk disease; the latter was fully accounted for by the close association between TP53 mutation and complex/monosomal karyotype while the observations regarding FLT3-ITD were not affected by treatment with midostaurin. AHSCT had a favorable impact on survival, most apparent in intermediate-1 (p <.001), intermediate-2 (p =.03), and high (p =.01) risk disease. The proposed 3-factor survival model offers a novel prototype that is amenable to further enhancement by molecular information and was validated in an external cohort of 1032 intensively-treated AML patients.
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U2 - 10.1002/ajh.26630
DO - 10.1002/ajh.26630
M3 - Article
C2 - 35702875
AN - SCOPUS:85133046706
SN - 0361-8609
VL - 97
SP - 1127
EP - 1134
JO - American journal of hematology
JF - American journal of hematology
IS - 9
ER -