Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1.
Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08-4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95-2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026-2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.
Hematopathology Unit, Pathology Department, and Hematology Department, IDIBAPS, Hospital Clínic, Barcelona, Spain.
María
M
Rozman
José-Tomás
JT
Navarro
Leonor
L
Arenillas
Anna
A
Aventín
Teresa
T
Giménez
Esther
E
Alonso
Granada
G
Perea
Mireia
M
Camós
Mayda
M
Navarrete
Esperanza
E
Tuset
Lourdes
L
Florensa
Fuensanta
F
Millá
Josep
J
Nomdedéu
Esmeralda
E
de la Banda
Marina
M
Díaz-Beyá
Marta
M
Pratcorona
Ana
A
Garrido
Blanca
B
Navarro
Salut
S
Brunet
Jorge
J
Sierra
Jordi
J
Esteve
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D019070:Cell Lineage; D002467:Cell Nucleus / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D012306:Risk; D055815:Young Adult
C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin