CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy.
The recently described single-nucleotide polymorphism CT60, located in the 3'-untranslated region of the CTLA4 (cytotoxic T-lymphocyte antigen 4 ) gene, has been associated with susceptibility to several autoimmune diseases and has also been shown to be involved in immune responses following allogeneic stem cell transplantation (SCT). However, the contribution of the CTLA4 genotype to the control of minimal residual disease in patients with acute myeloid leukemia (AML) has yet to be explored. We investigated the association between the CTLA4 CT60 A/G genotype and the incidence of leukemic relapse in 143 adult patients with AML in first complete remission after the same chemotherapy protocol (CETLAM LAM'03). The CT60 AA genotype was associated with a higher rate of leukemic relapse (56.4 vs 35.6%, P=0.004; hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.36-5.14) and lower overall survival at 3 years (39.4 vs 68.4%, P=0.004; HR=2.80, 95% CI=1.39-5.64). This is the first study to report an association between polymorphisms at CTLA-4 and AML relapse.
Pérez-García
A
A
Hematology Department, Institut Catalàd'Oncologia, Girona, L'Hospitalet and Badalona, Spain.
Brunet
S
S
Berlanga
J J
JJ
Tormo
M
M
Nomdedeu
J
J
Guardia
R
R
Ribera
J M
JM
Heras
I
I
Llorente
A
A
Hoyos
M
M
Esteve
J
J
Besalduch
J
J
Bueno
J
J
Sierra
J
J
Gallardo
D
D
D020413:3' Untranslated Regions / Q000235:genetics; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D055815:Young Adult
D020413:3' Untranslated Regions; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D009363:Neoplasm Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin