Treatment outcomes of childhood PICALM::MLLT10 acute leukaemias

Author:

Mark Catherine1ORCID,Meshinchi Soheil2,Joyce Brooklyn1,Gibson Brenda3,Harrison Christine4,Bergmann Anke K.5,Goemans Bianca F.6,Pronk Cornelis Jan H.7,Lapillonne Helene8,Leverger Guy8,Antoniou Evangelia9,Schneider Markus9,Attarbaschi Andishe1011ORCID,Dworzak Michael1011ORCID,Stary Jan12,Tomizawa Daisuke13,Ebert Sabine14,Lejman Monika15,Kolb E. Anders16,Schmiegelow Kjeld17,Hasle Henrik18,Abla Oussama1

Affiliation:

1. Division of Hematology/Oncology Toronto Hospital for Sick Children Toronto Ontario Canada

2. Fred Hutchinson Cancer Research Centre Seattle Washington USA

3. Royal Hospital for Sick Children Glasgow, Scotland UK

4. Newcastle University Centre for Cancer Newcastle UK

5. Human Genetics Hannover Medical School Hannover Germany

6. Princess Maxima Centre for Pediatric Oncology Utrecht The Netherlands

7. Skane University Hospital Lund Sweden

8. Hôpital d'enfants Armand Trousseau Paris France

9. Universitats‐Klinikum Essen Germany

10. Department of Pediatrics and Adolescent Medicine St. Anna Children's Hospital, Medical University of Vienna Vienna Austria

11. St. Anna Children's Cancer Research Institute (CCRI) Vienna Austria

12. Department of Pediatric Hematology and Oncology, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

13. Division of Leukemia and Lymphoma, Children's Cancer Centre National Centre for Child Health and Development Tokyo Japan

14. Clinic of Pediatric Hematology and Oncology University Medical Centre Hamburg Germany

15. Independent Laboratory of Genetic Diagnostics Medical University of Lublin Lublin Poland

16. Nemours Children's Hospital Wilmington Delaware USA

17. Rigshospitalet University Hospital Copenhagen Denmark

18. Hematology/Oncology, Department of Pediatrics Aarhus University Hospital Aarhus Denmark

Abstract

SummaryThe prognostic impact of PICALM::MLLT10 status in childhood leukaemia is not well described. Ten International Berlin Frankfurt Münster‐affiliated study groups and the Children's Oncology Group collaborated in this multicentre retrospective study. The presence of the PICALM::MLLT10 fusion gene was confirmed by fluorescence in situ hybridization and/or RNA sequencing at participating sites. Ninety‐eight children met the study criteria. T‐cell acute lymphoblastic leukaemia (T‐ALL) and acute myeloid leukaemia (AML) predominated 55 (56%) and 39 (40%) patients, respectively. Most patients received a chemotherapy regimen per their disease phenotype: 58% received an ALL regimen, 40% an AML regimen and 1% a hybrid regimen. Outcomes for children with PICALM::MLLT10 ALL were reasonable: 5‐year event‐free survival (EFS) 67% and 5‐year overall survival (OS) 76%, but children with PICALM::MLLT10 AML had poor outcomes: 5‐year EFS 22% and 5‐year OS 26%. Haematopoietic stem cell transplant (HSCT) did not result in a significant improvement in outcomes for PICALM::MLLT10 AML: 5‐year EFS 20% for those who received HSCT versus 23% for those who did not (p = 0.6) and 5‐year OS 37% versus 36% (p = 0.7). In summary, this study confirms that PICALM::MLLT10 AML is associated with a dismal prognosis and patients cannot be salvaged with HSCT; exploration of novel therapeutic options is warranted.

Publisher

Wiley

Subject

Hematology

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