A Long-term Survivor of Congenital KMT2A-R B-lymphoblastic Leukemia with Persistently Positive Bone Marrow MRD and Multiple CNS Relapses

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2025 Feb 27

PMID 40016709

Authors

Taxiarhia J Arabatzis

Biren Desai

Sandra Baril

Susan Rasul

Girmay Tekle-Yohannes

Michal Ann Miller

Affiliations

Soon will be listed here.

Abstract

Here we describe the case of an infant incidentally diagnosed with congenital KMT2A-rearranged (KMT2A-r) B-cell ALL on Day of Life 4. He received the first dose of intrathecal methotrexate on DOL 5, and induction systemic therapy on DOL 6. He demonstrated morphologic remission at the end of induction but had positive bone marrow. Minimal residual disease (MRD) was 1.4%. He experienced isolated CNS disease after consolidation and immunotherapy. At 8 months of age he underwent hematopoietic stem cell transplantation (HSCT). At 14 months of age he had medullary and CNS relapse, and at 16 months of age underwent CD19 CAR-T therapy. At 6 years of age he remains in remission with tolerable developmental delays and a good quality of life.

References

Guest E, Kairalla J, Devidas M, Hibbitts E, Carroll A, Heerema N . Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed -rearranged acute lymphoblastic leukemia: Children's Oncology Group trial AALL15P1. Haematologica. 2024; 109(12):3918-3927. PMC: 11609799. DOI: 10.3324/haematol.2024.285158. View

Pieters R, De Lorenzo P, Ancliffe P, Aversa L, Brethon B, Biondi A . Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. J Clin Oncol. 2019; 37(25):2246-2256. DOI: 10.1200/JCO.19.00261. View

Clesham K, Rao V, Bartram J, Ancliff P, Ghorashian S, OConnor D . Blinatumomab for infant acute lymphoblastic leukemia. Blood. 2020; 135(17):1501-1504. DOI: 10.1182/blood.2019004008. View

Tomizawa D . Evolution and optimization of therapies for acute lymphoblastic leukemia in infants. Int J Hematol. 2022; 117(2):162-172. DOI: 10.1007/s12185-022-03502-w. View

Ibrahimova A, Pommert L, Breese E . Acute Leukemia in Infants. Curr Oncol Rep. 2021; 23(3):27. DOI: 10.1007/s11912-021-01021-1. View

Kearns G, Abdel-Rahman S, Alander S, Blowey D, Leeder J, Kauffman R . Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003; 349(12):1157-67. DOI: 10.1056/NEJMra035092. View

Popov A, Tsaur G, Permikin Z, Fominikh V, Verzhbitskaya T, Riger T . Incidence and prognostic value of central nervous system involvement in infants with B-cell precursor acute lymphoblastic leukemia treated according to the MLL-Baby protocol. Pediatr Blood Cancer. 2022; 69(9):e29860. DOI: 10.1002/pbc.29860. View

Contreras Yametti G, Ostrow T, Jasinski S, Raetz E, Carroll W, Evensen N . Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions. Cancers (Basel). 2021; 13(8). PMC: 8069391. DOI: 10.3390/cancers13081847. View

Breese E, Krupski C, Nelson A, Perentesis J, Phillips C . Use of CD19-directed CAR T-Cell Therapy in an Infant With Refractory Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2020; 43(4):152-154. DOI: 10.1097/MPH.0000000000001857. View

10.

van der Sluis I, De Lorenzo P, Kotecha R, Attarbaschi A, Escherich G, Nysom K . Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia. N Engl J Med. 2023; 388(17):1572-1581. DOI: 10.1056/NEJMoa2214171. View

11.

Leahy A, Newman H, Li Y, Liu H, Myers R, DiNofia A . CD19-targeted chimeric antigen receptor T-cell therapy for CNS relapsed or refractory acute lymphocytic leukaemia: a post-hoc analysis of pooled data from five clinical trials. Lancet Haematol. 2021; 8(10):e711-e722. PMC: 9026766. DOI: 10.1016/S2352-3026(21)00238-6. View

12.

Moskop A, Pommert L, Thakrar P, Talano J, Phelan R . Chimeric antigen receptor T-cell therapy for marrow and extramedullary relapse of infant acute lymphoblastic leukemia. Pediatr Blood Cancer. 2020; 68(1):e28739. DOI: 10.1002/pbc.28739. View

13.

Brown P . Neonatal Leukemia. Clin Perinatol. 2021; 48(1):15-33. DOI: 10.1016/j.clp.2020.11.002. View

14.

Raj A, Talukdar S, Das S, Gogoi P, Das D, Bhattacharya J . Congenital leukemia. Indian J Hematol Blood Transfus. 2014; 30(Suppl 1):159-61. PMC: 4192207. DOI: 10.1007/s12288-013-0307-7. View

15.

Gandemer V, Bonneau J, Oudin C, Berbis J, Bertrand Y, Tabone M . Late effects in survivors of infantile acute leukemia: a study of the L.E.A program. Blood Cancer J. 2017; 7(1):e518. PMC: 5301036. DOI: 10.1038/bcj.2016.129. View

16.

Ishii E, Oda M, Kinugawa N, Oda T, Takimoto T, Suzuki N . Features and outcome of neonatal leukemia in Japan: experience of the Japan infant leukemia study group. Pediatr Blood Cancer. 2005; 47(3):268-72. DOI: 10.1002/pbc.20599. View

17.

Leung W, Hudson M, Zhu Y, Rivera G, Ribeiro R, Sandlund J . Late effects in survivors of infant leukemia. Leukemia. 2000; 14(7):1185-90. DOI: 10.1038/sj.leu.2401818. View

18.

Hunger S, McGavran L, Meltesen L, Parker N, Kassenbrock C, Bitter M . Oncogenesis in utero: fetal death due to acute myelogenous leukaemia with an MLL translocation. Br J Haematol. 1998; 103(2):539-42. DOI: 10.1046/j.1365-2141.1998.00994.x. View

19.

van der Linden M, Valsecchi M, De Lorenzo P, Moricke A, Janka G, Leblanc T . Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009; 114(18):3764-8. DOI: 10.1182/blood-2009-02-204214. View