Imatinib addition to intensive chemotherapy for the treatment of children and adolescents with Philadelphia-chromosome positive acute lymphoblastic leukemia (Phi-ALL): a multicenter study from the GATLA group.

VENESA GIMENEZ; EVANGELINA AGRIELO; MARIA LAURA RIZZI; VIRGINIA SCHUTTENBERG; IRENE LARRIPA; LORENA ZANELLA; CECILIA MURRAY; CECILIA RICHIERI; CRISTIAN FERRI; MARCELA GUTIERREZ; ALEJANDRA CEDOLA

Helsinski

Congreso; 11TH BIENNIAL CHILDHOOD LEUKEMIA AND LYMPHOMA SYMPOSIUM; 2018

BFM Study Group

Background: ALL- Phi positive are infrequent in pediatric patients (pt), with a poor outcome. The addition of tyrosine-kinase inhibitors to the intensive chemotherapy has shown to better outcome in many international trials.Objectives: to analyze clinical features, response and outcome of children included in the 2011 EsPh ALL like study, from the GATLA group, this study also evaluated minimal residual disease (MRD) by RQ PCR in different time point of the treatment.Methods: patients age 1-21 years, recruited to the current national multicenter trial of frontline treatment ( EsPh ALL like). Pts were eligible if t(9;22) was present by cytogenetic analysis or BCR ABL fusion transcript identified by RQ PCR. Pts with abnormal renal or hepatic function, or an active systemic infection were ineligible. Pts were enrolled between 2011 and 2017, and they were classified as good risk or poor risk according to the response to induction treatment. Imatinib was added at day 15 of the induction, in a daily orally dose, and continued during all protocol. Chemotherapy regimen was a Berlin-Frankfurt-Munster high risk backbone. Poor risk group were eligible for stem cell transplantation. Minimal residual disease (MRD) monitoring was carried out in 26 of the 62 enrolled pts; in two standardized centers of our country using RQ-PCR assays according to Biomed protocol. Bone marrow and/or peripheral blood samples were evaluated in some of the following stages: end of induction, previous of consolidation and during maintenance or post-allo HSCT. The BCR-ABL1 level was expressed as ratio between BCR-ABL1 copy number and ABL1 copy number. Sensitivity and quantitative range of quantitative PCR method were defined according to European guidelines. Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%. MMR was defined as a BCR-ABL1:ABL1 ratio ≤0.1% on the International Scale for p210 BCR-ABL1 or a 3-log reduction in transcripts for p190 BCR-ABL1.