Contributions
Abstract: EP358
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Many attempts have been made worldwide to improve a prognosis of infants, with 11q23/KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL). However, currently treatment outcome in infants with ALL is worse in comparison to older children.
Aims
To evaluate various prognostic factors (excluding MRD) in infant KMT2A-r B-cell precursor ALL enrolled in Russian-Belarus multicenter trial MLL-Baby
Methods
The study cohort comprised 100 consecutive infants aged 0–365 days with newly diagnosed KMT2A-r ALL enrolled between September 2003 and April 2016 (follow-up updated in January 2021). Among them there were 36 (36%) boys and 64 (64%) girls. Infants with translocation t(4;11)(q21;q23) were allocated to the high-risk (HR) arm, while all other KMTA2-r ALL patients who achieved complete remission (CR) by the end of induction (EOI) were treated by Intermediate-risk (ImR) arm. Only 2 of 100 patients were transplanted. EFS was estimated according to the Kaplan–Meier method [with Greenwood standard error (SE)], and differences between groups were compared using the log-rank test. The cumulative incidence of relapse (CIR) was estimated after adjusting for competing risks of other events and compared with the Gray test. Analysis of the prognostic relevance of various clinical and laboratory parameters was performed using the Cox model on the cause-specific hazard of event and the Wald test. Informed consent was obtained in all cases.
Results
EFS in the ImR group (n=50) of MLL-Baby trial was 35.1±6.9%, in the HR group (n=50) 38.3±7.1% (p=0.941). Patients older than 6 months (n=38) had better, but not statistically significant outcome (EFS 45.5±8,4%, CIR 43.3±8,7%) compared to younger than 6 mo infants (n=62) (EFS 31.2±6,0%, CIR 54.9±6,8%) (p=0.132 and p=0.245, correspondingly). Among various KMT2A rearrangements the most unfavorable prognosis had infants with translocation t(9;11)/ KMT2A-MLLT3: EFS 18.8±9.8%, CIR 75.0±9.7%. Intermediate results were obtained in patients with translocations t(4;11)/KMT2A–AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9±7,2% and 32,7±10.4%, respectively; CIR 46.3±7.8% and 50.9±12.3%. The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3±15.2%, CIR 0,0%. CD10-negative immunophenotype (n=72) neither influenced on outcome (p=0.897) nor on relapse risk (p=0.350). Initial CNS involvement led to lower EFS (p=0.007) and higher CIR (p=0.001) in comparison to patients without CNS leukemia. Dexamethasone good response on day 8 (n=82) was not associated with better treatment outcome (p=0.060 for EFS and p=0.332 for CIR). Alternatively, M1 status of BM on day 15 (n=72) improved both EFS (p=0.016) and CIR (p=0.002). So CR achievement on day 36 (n=97) did (p=0.001 for EFS). Multivariate analysis of hazard on unfavorable event showed that unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (n=44) (p=0.020), initial white blood cell count higher than 300×109/L (n=26) (p=0.028), M2/M3 bone marrow status on day 15 (p=0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p=0.012). EOI CR achievement (n=97) had borderline significance (p=0.051).
Conclusion
Our data revealed several prognostic factors that led to unfavorable outcome in infants with KMT2A-r ALL enrolled in MLL-Baby trial. We did not include MRD in this analysis as we previously showed its prognostic value (G. Tsaur et al doi.org/10.1111/bjh.17304).
Keyword(s): 11q23, Acute lymphoblastic leukemia, Infant, MLL
Abstract: EP358
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Many attempts have been made worldwide to improve a prognosis of infants, with 11q23/KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL). However, currently treatment outcome in infants with ALL is worse in comparison to older children.
Aims
To evaluate various prognostic factors (excluding MRD) in infant KMT2A-r B-cell precursor ALL enrolled in Russian-Belarus multicenter trial MLL-Baby
Methods
The study cohort comprised 100 consecutive infants aged 0–365 days with newly diagnosed KMT2A-r ALL enrolled between September 2003 and April 2016 (follow-up updated in January 2021). Among them there were 36 (36%) boys and 64 (64%) girls. Infants with translocation t(4;11)(q21;q23) were allocated to the high-risk (HR) arm, while all other KMTA2-r ALL patients who achieved complete remission (CR) by the end of induction (EOI) were treated by Intermediate-risk (ImR) arm. Only 2 of 100 patients were transplanted. EFS was estimated according to the Kaplan–Meier method [with Greenwood standard error (SE)], and differences between groups were compared using the log-rank test. The cumulative incidence of relapse (CIR) was estimated after adjusting for competing risks of other events and compared with the Gray test. Analysis of the prognostic relevance of various clinical and laboratory parameters was performed using the Cox model on the cause-specific hazard of event and the Wald test. Informed consent was obtained in all cases.
Results
EFS in the ImR group (n=50) of MLL-Baby trial was 35.1±6.9%, in the HR group (n=50) 38.3±7.1% (p=0.941). Patients older than 6 months (n=38) had better, but not statistically significant outcome (EFS 45.5±8,4%, CIR 43.3±8,7%) compared to younger than 6 mo infants (n=62) (EFS 31.2±6,0%, CIR 54.9±6,8%) (p=0.132 and p=0.245, correspondingly). Among various KMT2A rearrangements the most unfavorable prognosis had infants with translocation t(9;11)/ KMT2A-MLLT3: EFS 18.8±9.8%, CIR 75.0±9.7%. Intermediate results were obtained in patients with translocations t(4;11)/KMT2A–AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9±7,2% and 32,7±10.4%, respectively; CIR 46.3±7.8% and 50.9±12.3%. The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3±15.2%, CIR 0,0%. CD10-negative immunophenotype (n=72) neither influenced on outcome (p=0.897) nor on relapse risk (p=0.350). Initial CNS involvement led to lower EFS (p=0.007) and higher CIR (p=0.001) in comparison to patients without CNS leukemia. Dexamethasone good response on day 8 (n=82) was not associated with better treatment outcome (p=0.060 for EFS and p=0.332 for CIR). Alternatively, M1 status of BM on day 15 (n=72) improved both EFS (p=0.016) and CIR (p=0.002). So CR achievement on day 36 (n=97) did (p=0.001 for EFS). Multivariate analysis of hazard on unfavorable event showed that unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (n=44) (p=0.020), initial white blood cell count higher than 300×109/L (n=26) (p=0.028), M2/M3 bone marrow status on day 15 (p=0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p=0.012). EOI CR achievement (n=97) had borderline significance (p=0.051).
Conclusion
Our data revealed several prognostic factors that led to unfavorable outcome in infants with KMT2A-r ALL enrolled in MLL-Baby trial. We did not include MRD in this analysis as we previously showed its prognostic value (G. Tsaur et al doi.org/10.1111/bjh.17304).
Keyword(s): 11q23, Acute lymphoblastic leukemia, Infant, MLL