Minimal residual disease as biomarker for optimal biologic dosing of ARA-C in patients with acute myeloid leukemia.
We assessed by flow cytometry minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) given standard-dose (SDAC) and high-dose ARA-C (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18-59 years) qualified for analysis, all achieving complete remission after treatment with SDAC (n = 78) or HDAC (n = 52) plus etoposide and daunorubicin. Consolidation consisted of intermediate-dose ARA-C and daunorubicin. MRD negativity was significantly more frequent in the SDAC vs. HDAC arm after both induction (37% vs. 15%, P = 0.007) and consolidation (44% vs. 18%, P = 0.002). Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 × 10(-3) and 4 × 10(-3) (P = 0.033) after induction and 5.7 × 10(-4) and 2.9 × 10(-3) (P = 0.008) after consolidation. Based on ARA-C schedule and post-consolidation MRD status, the four patient groups (SDAC-MRD(-) , HDAC-MRD(-) , SDAC-MRD(+) , and HDAC-MRD(+) ) displayed 5-year overall survival rates of 60%, 33%, 24%, and 42% (P = 0.007), respectively, with 24%, 35%, 74%, and 48% (P < 0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a biomarker for optimal biologic dosing of ARA-C, and SDAC regimen appears to yield more frequent MRD negativity.
Ematologia, Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Roma, Italia.
Luca
L
Maurillo
Francesco
F
Buccisano
Alfonso
A
Piciocchi
Maria Ilaria
MI
Del Principe
Chiara
C
Sarlo
Ambra
A
Di Veroli
Paola
P
Panetta
Maria
M
Irno-Consalvo
Daniela
D
Nasso
Concetta
C
Ditto
Marco
M
Refrigeri
Gottardo
G
De Angelis
Raffaella
R
Cerretti
William
W
Arcese
Giuseppe
G
Sconocchia
Francesco
F
Lo-Coco
Sergio
S
Amadori
Adriano
A
Venditti
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D054316:Biomarkers, Pharmacological / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis
D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D003561:Cytarabine; D005047:Etoposide; D003630:Daunorubicin