The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy.
A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2-202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively (P<0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease (P<0.001), IGHV status (P<0.001) and β2-microglobulin levels (P=0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity (P=0.014), together with advanced age (P<0.001), unmutated IGHV status (P=0.001), TP53 mutations (P<0.001) and elevated levels of β2-microglobulin (P=0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.
jdelgado@clinic.ub.es.
Rodrigo
R
Santacruz
Neus
N
Villamor
Marta
M
Aymerich
Alejandra
A
Martínez-Trillos
Cristina
C
López
Alba
A
Navarro
María
M
Rozman
Sílvia
S
Beà
Cristina
C
Royo
Maite
M
Cazorla
Dolors
D
Colomer
Eva
E
Giné
Magda
M
Pinyol
Xose S
XS
Puente
Carlos
C
López-Otín
Elías
E
Campo
Armando
A
López-Guillermo
Julio
J
Delgado
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome