The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia

Overview

Journal Cancer Res Treat

Specialty Oncology

Date 2024 Jul 5

PMID 38965922

Authors

Hee Young Ju

Na Hee Lee

Eun Sang Yi

Young Bae Choi

So Jin Kim

Ju Kyung Hyun

Hee Won Cho

Jae Kyung Lee

Ji Won Lee

Ki Woong Sung

Hong Hoe Koo

Keon Hee Yoo

Affiliations

Soon will be listed here.

Abstract

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.

Materials And Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients' disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.

Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.

Conclusion: HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

References

Pulsipher M, Langholz B, Wall D, Schultz K, Bunin N, Carroll W . Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?. Bone Marrow Transplant. 2015; 50(9):1173-9. PMC: 4573663. DOI: 10.1038/bmt.2015.103. View

Luo L, Jiao Y, Li Y, Yang P, Gao J, Huang S . Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for adolescent and adult Tlymphoblastic leukemia /lymphoma: a large cohort multicenter study in China. Ann Hematol. 2024; 103(6):2073-2087. DOI: 10.1007/s00277-024-05719-7. View

Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I . Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood. 2010; 116(15):2644-50. DOI: 10.1182/blood-2010-03-273532. View

Schultz K, Carroll A, Heerema N, Bowman W, Aledo A, Slayton W . Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014; 28(7):1467-71. PMC: 4282929. DOI: 10.1038/leu.2014.30. View

Shyr D, Davis K, Bertaina A . Stem cell transplantation for ALL: you've always got a donor, why not always use it?. Hematology Am Soc Hematol Educ Program. 2023; 2023(1):84-90. PMC: 10726989. DOI: 10.1182/hematology.2023000423. View

Dunsmore K, Winter S, Devidas M, Wood B, Esiashvili N, Chen Z . Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020; 38(28):3282-3293. PMC: 7526719. DOI: 10.1200/JCO.20.00256. View

Biondi A, Gandemer V, De Lorenzo P, Cario G, Campbell M, Castor A . Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial. Lancet Haematol. 2018; 5(12):e641-e652. DOI: 10.1016/S2352-3026(18)30173-X. View

Advani A, Moseley A, ODwyer K, Wood B, Park J, Wieduwilt M . Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia. Blood Adv. 2022; 7(7):1279-1285. PMC: 10090098. DOI: 10.1182/bloodadvances.2022008216. View

Hirabayashi S, Kondo T, Nishiwaki S, Mizuta S, Doki N, Fukuda T . Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph ALL: A retrospective nationwide study. Am J Hematol. 2023; 98(10):1606-1618. DOI: 10.1002/ajh.27041. View

10.

Yeshurun M, Weisdorf D, Rowe J, Tallman M, Zhang M, Wang H . The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Adv. 2019; 3(4):670-680. PMC: 6391668. DOI: 10.1182/bloodadvances.2018027003. View

11.

Issa G, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M . The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023; 615(7954):920-924. PMC: 10060155. DOI: 10.1038/s41586-023-05812-3. View

12.

van der Velden V, Corral L, Valsecchi M, Jansen M, de Lorenzo P, Cazzaniga G . Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009; 23(6):1073-9. DOI: 10.1038/leu.2009.17. View

13.

Gu Z, Li F, Li M, Wang L, Lu N, Jin X . Upfront allogeneic hematopoietic stem cell transplantation for adult T-cell acute lymphoblastic leukemia/lymphoma in first complete remission: a single-center study. Ann Hematol. 2024; 103(7):2445-2454. DOI: 10.1007/s00277-024-05716-w. View

14.

Foa R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo M . Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020; 383(17):1613-1623. DOI: 10.1056/NEJMoa2016272. View

15.

Hunger S, Tran T, Saha V, Devidas M, Valsecchi M, Gastier-Foster J . Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2023; 10(7):e510-e520. DOI: 10.1016/S2352-3026(23)00088-1. View

16.

Dreyer Z, Dinndorf P, Camitta B, Sather H, La M, Devidas M . Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group. J Clin Oncol. 2010; 29(2):214-22. PMC: 3058277. DOI: 10.1200/JCO.2009.26.8938. View

17.

Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P . The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: an evidence-based review. Biol Blood Marrow Transplant. 2005; 11(11):823-61. DOI: 10.1016/j.bbmt.2005.08.035. View

18.

Prockop S, Wachter F . The current landscape: Allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia. Best Pract Res Clin Haematol. 2023; 36(3):101485. DOI: 10.1016/j.beha.2023.101485. View

19.

Peters C, Dalle J, Locatelli F, Poetschger U, Sedlacek P, Buechner J . Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2020; 39(4):295-307. PMC: 8078415. DOI: 10.1200/JCO.20.02529. View

20.

Jabbour E, Short N, Jain N, Huang X, Montalban-Bravo G, Banerjee P . Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2022; 10(1):e24-e34. DOI: 10.1016/S2352-3026(22)00319-2. View