Cancer Res Treat.  2025 Jan;57(1):240-249. 10.4143/crt.2024.155.

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

• Ju HY
• Lee NH
• Yi ES
• Choi YB
• Kim SJ
• Hyun JK
• Cho HW
• Lee JK
• Lee JW
• Sung KW
• Koo HH
• Yoo KH

• KMID: 2564597
• DOI: http://doi.org/10.4143/crt.2024.155

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.

Keyword

Precursor cell lymphoblastic leukemia-lymphoma; Hematopoietic stem cell transplantation; Survival; Precursor T-cell lymphoblastic leukemia-lymphoma

Figure

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  Fig. 1. Study population. ALAL, acute leukemia of ambiguous lineage; ALL, acute lymphoblastic leukemia.

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  Fig. 2. Survival outcome according to clinical factors and treatment. (A) Overall survival of total patients with or without hematopoietic stem cell transplantation (HSCT). (B) Overall survival of the patients who underwent HSCT (by indication). (C) Overall survival of total patients according to HSCT period. (D) Overall survival of B-cell acute lymphoblastic leukemia (B-ALL) patients with or without HSCT. (E) Overall survival of T-cell acute lymphoblastic leukemia (T-ALL) patients with or without HSCT. (F) Overall survival of patients of B-ALL patients who underwent HSCT, by indication. (G) Overall survival of patients of T-ALL patients who underwent HSCT, by indication. (H) Overall survival by cytogenetic groups, with or without HSCT.

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  Fig. 3. Effect of hematopoietic stem cell transplantation (HSCT) on treatment result in different subgroups, based on whether HSCT is adopted as primary treatment or not (other cytogenetics group: other than KMT2A, Philadelphia chromosome–positive, hypodiploidy, hyperdiploidy, ETV6::RUNX1). (A) Event-free survival of KMT2A-rearranged acute lymphoblastic leukemia (ALL). (B) Overall survival of KMT2A-rearranged ALL. (C) Event-free survival of other cytogenetics group. (D) Overall survival of other cytogenetics group.

Reference

References

1. Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol. 2015; 33:2938–48.

2. Yeshurun M, Weisdorf D, Rowe JM, Tallman MS, Zhang MJ, Wang HL, et al. The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Adv. 2019; 3:670–80.

3. Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, et al. 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; 11:823–61.

4. Prockop S, Wachter F. The current landscape: allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia. Best Pract Res Clin Haematol. 2023; 36:101485.

5. Kanate AS, Majhail NS, Savani BN, Bredeson C, Champlin RE, Crawford S, et al. Indications for hematopoietic cell transplantation and immune effector cell therapy: guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2020; 26:1247–56.

6. Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll W, et al. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested? Bone Marrow Transplant. 2015; 50:1173–9.

7. Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, et al. 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. 2011; 29:214–22.

8. Dreyer ZE, Hilden JM, Jones TL, Devidas M, Winick NJ, Willman CL, et al. Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). Pediatr Blood Cancer. 2015; 62:419–26.

9. Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I, et al. 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; 116:2644–50.

10. Van der Velden VH, Corral L, Valsecchi MG, Jansen MW, De Lorenzo P, Cazzaniga G, et al. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009; 23:1073–9.

11. Attarbaschi A, Moricke A, Harrison CJ, Mann G, Baruchel A, De Moerloose B, et al. Outcomes of childhood noninfant acute lymphoblastic leukemia with 11q23/KMT2A rearrangements in a modern therapy era: a retrospective international study. J Clin Oncol. 2023; 41:1404–22.

12. Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023; 615:920–4.

13. Gu Z, Li F, Li M, Wang L, Lu N, Jin X, et al. 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; 103:2445–54.

14. Luo L, Jiao Y, Li Y, Yang P, Gao J, Huang S, et al. Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for adolescent and adult T-lymphoblastic leukemia/lymphoma: a large cohort multicenter study in China. Ann Hematol. 2024; 103:2073–87.

15. Zhang X, Pang Y, Wei C, Liang D, Yang S, Zhao C, et al. Role of allogeneic hematopoietic stem cell transplantation in patients with high-risk T-cell lymphoblastic leukaemia/lymphoma: an analysis of clinical outcomes. Bone Marrow Transplant. 2024; 59:422–4.

16. Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, et al. 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; 38:3282–93.

17. Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children’s Oncology Group study AALL0031. Leukemia. 2014; 28:1467–71.

18. Biondi A, Gandemer V, De Lorenzo P, Cario G, Campbell M, Castor A, et al. Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, singlearm clinical trial. Lancet Haematol. 2018; 5:e641–52.

19. Hunger SP, Tran TH, Saha V, Devidas M, Valsecchi MG, Gastier-Foster JM, et al. 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:e510–20.

20. Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerjee P, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023; 10:e24–34.

21. Foa R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al. Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020; 383:1613–23.

22. Advani AS, Moseley A, O’Dwyer KM, Wood BL, Park J, Wieduwilt M, et al. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia. Blood Adv. 2023; 7:1279–85.

23. Hirabayashi S, Kondo T, Nishiwaki S, Mizuta S, Doki N, Fukuda T, et al. 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; 98:1606–18.

24. Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, et al. Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority phase III study. J Clin Oncol. 2021; 39:295–307.

25. Shyr D, Davis KL, 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; 2023:84–90.