Frequency and prognostic significance of t(v;11q23)/KMT2A rearrangements in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.
The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study. Complete response (CR) was attained in 38 patients; 25 remained in CR after consolidation. Twelve (48%) received allogeneic hematopoietic stem cell transplantation (HSCT) and 13 delayed intensification and maintenance. The 5-year CR duration probability was 37% (95% CI, 19%-55%). A trend for a longer CR duration was observed in patients undergoing HSCT vs. those receiving chemotherapy. The 5-year overall survival (OS) probability was 20% (95% CI, 5%-35%). The OS was better, albeit not significant, in patients with a MRD level <0.1% after induction (39% [95% CI, 14%-64%] vs. 13% [95% CI, 0%-36%]). Specific treatment approaches are required to improve the outcome of patients with KMT2A-rearrangements.
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Cristina
C
Motlló
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Josep-Maria
JM
Ribera
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Mireia
M
Morgades
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Isabel
I
Granada
b Department of Hematology , Hospital Universitario y Politécnico La Fe , Valencia , Spain.
Pau
P
Montesinos
c Department of Hematology , Hospital de Sant Pau , Barcelona , Spain.
Salut
S
Brunet
d Department of Hematology , Hospital San Pedro de Alcántara , Cáceres , Spain.
Juan
J
Bergua
e Department of Hematology , Hospital Clínico Universitario , Valencia , Spain.
Mar
M
Tormo
f Department of Hematology , Hospital General , Castellón , Spain.
Raimundo
R
García-Boyero
g Department of Hematology , ICO-Hospital Duran i Reynals, L'Hospitalet del Llobregat , Spain.
Josep
J
Sarrà
h Department of Hematology , Hospital Clínico San Carlos , Madrid , Spain.
Eloy
E
Del Potro
i Department of Hematology , Hospital 12 de Octubre , Madrid , Spain.
Carlos
C
Grande
j Department of Hematology , Hospital Vall d'Hebron , Barcelona , Spain.
Pere
P
Barba
k Department of Hematology , Hospital Universitario Central de Asturias , Oviedo , Spain.
Teresa
T
Bernal
l Department of Hematology , Hospital Morales Messeguer , Murcia , Spain.
María-Luz
ML
Amigo
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Javier
J
Grau
b Department of Hematology , Hospital Universitario y Politécnico La Fe , Valencia , Spain.
José
J
Cervera
a Department of Hematology , ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona , Badalona , Spain.
Evarist
E
Feliu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D003131:Combined Modality Therapy; D005260:Female; D005787:Gene Frequency; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
KMT2A/MLL; MRD; acute lymphoblastic leukemia