A Plateau after 30 Months of Follow-Up in B -Lineage Childhood Acute Lymphoblastic Leukemia (ALL) with t(1;19)(q23;p13)/E2A-PBX1?.

Late events are observed in B-lineage ALL with no plateau seen if a sufficient observation period is provided. The prognosis of childhood ALL associated to the t(1;19)(q23;p13)/E2A-PBX1 translocation has improved over the two last decades. The purpose of this study is to define the kinetics of relapse in a large cohort of children and to raise the possibility of a plateau in that entity. We identified 110 children treated for a B-lineage ALL harbouring a t(1;19(q23;p13) and/or E2A-PBX1 fusion transcript from 1987 to 2004 in the FRALLE protocols (FRALLE 83: n= 3, FRALLE 87–89: n=18, FRALLE 92 (phase II): n=10, FRALLE 93: n=48, FRALLE 2000 (still opened: n=31). Analysed features included: male sex (50, 45%), age (median: 6.9y; Q1–Q3: 3.5–12), CNS disease (4, 3.5%), leucocytosis (median: 21.4 G/L; Q1–Q3: 10.8–53.4), D8 poor prednisone response (PPR) (5/79, 6%), M1 D21 marrow response (103, 94%), and CR (108, 98%). For an accurate comparison, the subgroup of pts with t(1;19) included in the FRALLE 93 protocol (n=48) was compared to the 1,147 children aged more than 1 y with B- lineage ALL treated in the same protocol. Significant differences in the t(1;19) cohort were: excess of girls (65% vs. 46%; p= .01), and older age (median: 7 vs. 4.7; p= .01)). No differences in early response to treatment (D8, D21, D35) were seen. All the 110 patients received chemotherapy only, except 3 who received an autologous BMT for D8 PPR as recommended by the FRALLE 93 protocol. At a median FU of 65 months, 18 events have been recorded including 17 relapses (bone marrow: 13, CNS: 4) and 1 secondary tumor (abdominal Burkitt lymphoma) giving a 5 y and 10 y EFS of 78.7%. If “modern era” only is considered (> 1992), 5 y and 10 y EFS is 85.5%. Relapses occurred at a median time of 422 days (range: 72–899) in the whole t(1;19) cohort. In those from FRALLE 93, the median time to relapse (MTTR) was 280 days, that is significantly lower than the one observed in the control group defined above (MTTR = 894 days, Wilcoxon test, p = .01).

Conclusions: We confirm that a high cure rate is now associated to that subgroup of childhood ALL. The main finding is that no event except from the secondary Burkitt lymphoma (1705 d) was registered after 30 months from diagnosis in that cohort of 110 children with t(1;19)/E2A-PBX1 translocation associated ALL. It is then conceivable to announce cure at 36 months in that subgroup with an extremely low possibility of mistake, thus much earlier and with more confidence than in the other B-lineage ALL.