Prognostic role of minimal residual disease in mature B-cell acute lymphoblastic leukemia of childhood.
OBJECTIVE
To study the prevalence of t(8;14) at diagnosis and the response kinetics to treatment of minimal residual disease (MRD) in B-cell acute lymphoblastic leukemia (B-ALL) patients and determine its impact on prognosis.


METHODS
A total of 68 children affected by de novo B-ALL enrolled onto the Berlin-Frankfurt-Muenster-based Italian Association of Pediatric Hematology and Oncology LNH-97 clinical protocol were studied. Bone marrow aspirate from each patient was analyzed for the presence of t(8;14)(q24;q32) by long-distance polymerase chain reaction at diagnosis, after the first chemotherapy cycle, and after subsequent cycles until negative for MRD. Morphologic and immunophenotypic analyses were reviewed centrally.


RESULTS
A total of 47 patients (69%) were positive for t(8;14)(q24;q32). MRD response kinetics was determined in 39 patients. All of them reached clinical complete remission and most (31 of 39) became MRD negative after the first chemotherapy cycle. The 3-year relapse-free survival (RFS) was 38% (SE = 17%) in patients MRD positive after the first chemotherapy cycle compared with 84% (SE = 7%) in MRD-negative patients (P = .0005), whereas there was no difference in RFS for children who reached a clinical complete remission after the first chemotherapy cycle versus those who did not (RFS = 72% and SE = 9%; RFS = 79% and SE = 11%, respectively; P = .8). In multivariate analysis, MRD was shown to be predictive of higher risk of failure.


CONCLUSIONS
Our study demonstrated that MRD carries a negative prognostic impact in B-ALL patients and suggests that a better risk-adapted therapy, possibly including the use of anti-CD20 monoclonal antibody, should be considered in selected patients.
Mussolin
Lara
L
Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, Via Giustiniani 3, 35128 Padova, Italy.
Pillon
Marta
M
Conter
Valentino
V
Piglione
Matilde
M
Lo Nigro
Luca
L
Pierani
Paolo
P
Micalizzi
Concetta
C
Buffardi
Salvatore
S
Basso
Giuseppe
G
Zanesco
Luigi
L
Rosolen
Angelo
A
D000293:Adolescent; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006801:Humans; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D014178:Translocation, Genetic
D007770:L-Lactate Dehydrogenase