Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia.
A total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD(-) had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD(+) had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD(-) status, had a better outcome than those who remained MRD(+) (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD(-) with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD(+) categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy.
Buccisano
Francesco
F
Hematology, Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, Italy.
Maurillo
Luca
L
Spagnoli
Alessandra
A
Del Principe
Maria Ilaria
MI
Fraboni
Daniela
D
Panetta
Paola
P
Ottone
Tiziana
T
Consalvo
Maria Irno
MI
Lavorgna
Serena
S
Bulian
Pietro
P
Ammatuna
Emanuele
E
Angelini
Daniela F
DF
Diamantini
Adamo
A
Campagna
Selenia
S
Ottaviani
Licia
L
Sarlo
Chiara
C
Gattei
Valter
V
Del Poeta
Giovanni
G
Arcese
William
W
Amadori
Sergio
S
Lo Coco
Francesco
F
Venditti
Adriano
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3