Abstract: LB173

Type: Poster Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 17:15 - 18:45

Location: Poster area (Hall H)

Background
Compared with children, adults with acute lymphoblastic leukemia (ALL) have had inferior survival, when treated with traditional adult ALL regimens.

Aims
The aim of this study was to examine the event free survival (EFS) of children and adults with ALL (1-45 years) diagnosed, risk stratified, and treated uniformly according to the NOPHO ALL2008 protocol.

Methods
We collected information on 1509 patients from Sweden, Norway, Iceland (children only), Finland (children only), Denmark, Lithuania, and Estonia diagnosed 7/2008-12/2014 with Ph-negative ALL and treated according to the NOPHO ALL2008 protocol. Patients were registered in the NOPHO ALL2008 database upon diagnosis and subsequently followed systematically at three months intervals.

Results
Of 1509 patients, 1022 were children 1-9 years (484 female), 266 were 10-17 years (106 female) and 221 were adults 18-45 years (85 females). Adult patients more often had T-ALL (9% (1-9 years),  25% (10-17 years) and 32% (18-45 years), p<0.001), and KMT2A (a.k.a MLL) rearrangements (KMT2A-r, 3% (1-9 years), 5% (10-17 years)  and 6% (18-45 years), p<0.001), but lower median WBC when stratified by lineage (B-lineage 9.9 (1-9 years), 8.1 (10-17 years) and 6.8 (18-45 years) x10⁹/L, p=0.01; T-lineage 134 (1- 9 years), 71.7 (10-17 years) and 38.8 (18-45 years) x10⁹/L, p<0.001). Day 29 MRD was significantly higher for adults (p<0.001). Based on immunophenotype, WBC at diagnosis, MRD (discriminator 0.1%, FCM for BCP and PCR for T) at day 29 and 79, and presence of intermediate (dic(9:20) or iAMP21[RUNX1] or t(1;19)) or  high risk cytogenetics (KMT2A-r or hypodiploidy (modal number <45)), patients were stratified into 4 risk groups (SR, IR, HR, and HR+hSCT, Table 1). Only MRD d29 >­5% or d79>0.1% stratified to hSCT in 1^st complete remission (CR1). Older patients were skewed towards higher risk group (Toft, Eur J Haematol 2013), but for each treatment arm severe toxicities (except for thrombosis and osteonecrosis) and intervals between treatment phases were almost identical for children and adults (Toft, Eur J Haematol 2015).After a median follow up for patients in CR1 of 4.0 years (75% range: 2.4-5.9 years), 16 patients (3 patients 18-45 years) had died during induction (induction failure), and 50 patients (12 patients 18-45 years) had died in first remission. A total of 123 patients relapsed (36 patients 18-45 years), and 12 children and 1 adult developed a second malignancy. The overall 5y-EFS for patients 1-9, 10-17 and 18-45 years was 88% (95%CI: 86; 90), 79% (95%CI: 73; 85) and 73% (95%CI: 67; 79), respectively, p <0.001. However, when stratified by risk group, the poorer EFS for adults was significant only for patients with intermediate risk ALL (Table 1).

Conclusion
The EFS for adult ALL patients has improved markedly with NOPHO ALL2008 treatment compared with historical data. Although adult patients more often have higher risk ALL, their overall cure rates are close to those of children when stratified by risk group.



Session topic: Acute lymphoblastic leukemia - Clinical 1

Keyword(s): Adult, ALL, Children, Treatment