Program DHC-Virtual
20 - 21 January 2021
Abstracts Lymphoid session 4
Abstract
Outcome of ABL-class ALL in children in the pre-tyrosine kinase inhibitor era
21 January
11:30 11:42
J. Boer
Paper

 

Outcome of ABL-class acute lymphoblastic leukemia in children in the pre-tyrosine kinase inhibitor era; an international retrospective study of the Ponte di Legno group

 

Judith Boer (1), Monique den Boer (1), Gunnar Cario (3), Anthony Moorman (4), Hester de Groot-Kruseman (1), Marta Fiocco (1,2), Gabriele Escherich (6), Toshihiko Imamura (7), Allen Yeoh (8), Rosemary Sutton (9), Luciano Dalla-Pozza (9), Nobutaka Kiyokawa (10), Martin Schrappe (3), Kathryn Roberts (11), Charles Mullighan (11), Stephen Hunger (12,14), Ajay Vora (5), Andishe Attarbaschi (15), Marketa Zaliova (16), Sara Elitzur (17), Giovanni Cazzaniga (18), Andrea Biondi (18), Mignon Loh (12,13), Rob Pieters (1)
(1) Prinses Máxima Centre for Pediatric Oncology, Dutch Childhood Oncology Group (DCOG), Utrecht, (2) Leiden University, Institute of Mathematics, Leiden, (3) University Hospital Schleswig-Holstein, AIEOP/BFM-Germany, Kiel, (4) Newcastle University, UK-ALL study group, Leukaemia Research Cytogenetics Group, Wolfson Childhood Cancer Research Centre,, Newcastle upon Tyne, (5) Great Ormond Street Hospital, Department of Haematology, London, (6) University Medical Center Hamburg Eppendorf, COALL study group, Hamburg, (7) Graduate School of Medical Science, JACLS study group, Department of Pediatrics, Kyoto, (8) National University of Singapore, Ma-Spore study group, Khoo Teck Puat - National University Children's Medical Institute, Yong Loo Li, Singapore, (9) University of New South Wales and Cancer Centre for Children-Children’s Hospital at Westmead, ANZCHOG study group, Children’s Cancer Institute, Sydney, (10) National Research Institute for Child and Development, TCCSG study group, Department of Pediatric Hematology and Oncology Research, Tokyo, (11) St Jude Children's Research Hospital, SJCRH study group, Memphis, (12) COG study group, COG study group, Monrovia, (13) Benioff Children’s Hospital and the Helen Diller Family Comprehensive Cancer Center, University of C, Department of Pediatrics, San Francisco, (14) Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsyl, Department of Pediatrics and the Center for Childhood Cancer Research, Pennsylvania, (15) St. Anna Kinderspital, AIEOP-BFM Austria, Vienna, (16) University Hospital Motol, AIEOP-BFM Czech Republic, Prague, (17) Schneider Children’s Medical Center of Israel, AIEOP-BFM Israel, Petach Tikvah, (18) Universtà di Milano-Bicocca, S. Gerardo Hospital, AIEOP-BFM Italy, Monza
No potential conflicts of interest
Introduction

 

In the last decade, it has become clear that ABL-class gene fusions other than BCR-ABL1 are detected in ~3% of children with acute lymphoblastic leukemia (ALL). Preclinical studies suggest that leukemic cells carrying ABL-class fusions can be targeted successfully by tyrosine kinase inhibitors (TKIs). The addition of TKIs to the therapy of BCR-ABL1-positive ALL has significantly improved the outcome but it is unknown whether this holds true for ALL with other ABL-class fusions. Moreover, the ABL-class fusion group is heterogeneous and includes patients with ABL1, ABL2, CSF1R and PDGFRB fusion types. The outcome for patients with these subtypes of ALL is not known because their occurrences are rare. This international study establishes the baseline characteristics and outcome of ABL-class ALL patients in the pre-TKI era.

 

Methods

 

Patients’ characteristics and outcome of 122 children with ABL-class B-cell precursor ALL were retrospectively collected through the Ponte di Legno consortium. Patients were enrolled in pediatric trials between 2000 and 2018 and were not exposed to TKIs during their first-line protocols. Event-free (EFS) and overall survival (OS) were determined by Kaplan-Meier methodology, and the cumulative incidence of relapse (CIR) and treatment-related mortality by a competing risk model.

 

Results

 

Outcome of all ABL-class cases at 5 years was 31.0% (SD 4.6) for CIR, 59.1% (95%CI 50.5-69.1) for EFS and 76.1% (95%CI 68.6-84.5) for OS. ABL-class patients displayed a high frequency of poor prednisone response (49%) and IKZF1 deletions (61%), but both features lacked prognostic value. MRD-levels at the end of induction therapy (EOI) were very high (≥1x10-2) in 66% of ABL-class cases, and most prevalent detected in ABL2 (86%) and PDGFRB-fusion (88%) cases. MRD-EOI ≥1x10-2 was predictive of an unfavorable outcome among ABL-class patients (HREFS 3.33, 95%CI 1.46-7.56; p=0.0039. The 5-year EFS was 80% (95%CI 58.7-100) for CSF1R (n=10), 68.6% (95%CI 54.5-86.3) for ABL1 (n=40), 52.9% (95%CI 41.5-67.5) for PDGFRB (n=64), and 37.5% (95%CI 15.3-91.7) for ABL2 (n=8) fusion cases (p=0.059). Sixty-nine percent of relapses (25 of 36) occurred within 3 years after diagnosis. The 5-years CIR of patients who received hematopoietic stem cell transplantation (n=41; 17.8% SD 6.2) was lower compared to the non-transplanted group (n=43; 45.1% SD 8.4; p=0.013), but EFS and OS did not differ between the two groups.

 

Conclusion

 

Children with ABL-class B-ALL have a poor outcome on therapies without TKIs despite the use of high-risk chemotherapy regimens and frequent transplantation in first remission. This paper provides baseline outcome for evaluating the potential benefit of upfront TKI usage in ABL-class patients.

 

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