Allogeneic hematopoietic stem cel l transplantation in children’s acute myeloblastic leukemia:Survivaland relapse

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Published Jan 22, 2026
https://doi.org/10.62438/tunismed.v103i11.5353
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Vol. 103 No. 11 (2025): Tunis Med Nov 2025

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Nour Ben Abdeljelil
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
https://orcid.org/0000-0001-9529-4192
Insaf Ben Yaiche
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Riheb Ouerghi
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Ines Turki
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Lamia Torjemane
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Dorra Belloumi
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Sabrine Mekni
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Rimel Kanoun
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Anna Chabaane
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Saloua Ladeb
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia
Tarek Ben Othman
Hematology and Transplantation Service, National Bone Marrow Transplant Center, 1006, Faculty of Medicine of Tunis, University of Tunis El Manar, 1007, Tunis, Tunisia

Abstract

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated for children with high-risk (HR) acute myeloid leukemia (AML).
Objective: To evaluate over all survival (OS), event-free survival (EFS), relapse, and non-relapse mortality (NRM).
Methods: This was a retrospective descriptive studyincludingchildren (<18 years) with AML whounderwent allo-HSCT from an HLA-identical sibling donorbetween 1999 and 2023. Conditioningregimensconsisted of busulfan–cyclophosphamide (BuCy) or total body irradiation–cyclophosphamide (TBI–Cy). Stem cell sources were bone marrow (BM) or peripheral blood stem cells.
Results:Fifty-two children were included, with a medianage of 13 years (range: 3–17). Patients were classified as HR in 60.3% of cases. The median time fromdiagnosis to transplantation was 5 months (range: 3–40). At transplantation, 75% of patients were in first completeremission (CR1). The stem cell source was BM in 84.6% of cases, and BuCy wasusedin 90.4% of patients. The graft rejection rate was 5.8%. The cumulative incidences of acute and chronicgraft-versus-host disease (GVHD) were 20% and 23.4%, respectively. The cumulative incidence of NRM was 7.7%, while relapse occurred in 44.7% of patients. After a median follow-up of 30 months (range: 39 days–18 years), the 3-year OS and EFS were 51.6% and 47.8%, respectively.
Conclusion: Post–allo-HSCT relapse remains a major challenge in pediatric AML. Intensification of pre-transplant conditioning, busulfanpharmacokinetic monitoring, and the development of targetedtherapiesmay help reduce the risk of relapse.

Keywords:

Allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia, relapse, survival

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References

  1. PuiCH,CarrollWL,MeshinchiS,ArceciRJ.Biology,Risk Stratification ,and Therapy of Pediatric Acute
  2. Leukemias: An Update.JClinOncol.2011;29(5):551‑65.
  3. HarrisonCJ, HillsRK,MoormanAV,Grimwade DJ,HannI,Webb DK,et al.Cytogenetics of childhood acute
  4. myeloid leukemia:United Kingdom MRC treatment trials AML 10 and 12.J Clin Oncol2010;28:2674-81.
  5. Kharfan-DabajaMA,KumarA,AyalaE,AljurfM,NishihoriT,MarshR,etal.Standardizing Definitions of
  6. Hematopoietic Recovery,Graft Rejection, Graft Failure,Poor Graft Function,and Donor Chimerismin
  7. Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation
  8. and Cellular Therapy.Transplant Cell Ther.2021;27(8):642‑9.
  9. BenOthmanT,TorjemaneL,AbdelkefiA,LakhalA,LadebS,BenHamedL,etal.Allogeneic hematopoietic
  10. stem cell transplantation in Tunisia.BMT.2008Aug:42Suppl1:S139-S141.
  11. Ben AbdeljelilN,KanounRY,MekniS,TurkiI,BenYaicheI,OuerghiR,etal.Busulfan-cyclophosphamidevs
  12. fludarabine-busulfan for allogeneic transplantin acute myeloid leukemia.Future Oncol.2025;21(15):1887-1894.
  13. HaouasH,HaouasS,HafsiaA.A retrospectives tudy of leukemia epidemiology in Northern Tunisia.Hematology
  14. ;16(3):151-4.
  15. GmidèneA,SennanaH,WahchiI,BenYoussefY,JeddiR,ElloumiM,etal.Cytogenetic profile of a large
  16. cohort of Tunisian denovo acute myeloid leukemia.Hematology.2012;17(1):9-14.
  17. BakhtiarS,Salzmann-ManriqueE,HutterM,KrennT,DuerkenM,FaberJ,etal.Allo HSCT in paediatric ALL
  18. and AML in complete remission: improvement over time impacted by accreditation?Bone Marrow Transplant.
  19. ;54(5):737‑45.
  20. DohertyEE,RedellM,SasaG,YassineK,JohnTD,CraddockJ,etal. Outcomes after Allogeneic Hematopoietic
  21. Stem Cell Transplantation for Pediatric Acute Myeloid Leukemia in the Contemporary Era.Blood.
  22. ;134(Supplement_1):2056.
  23. PochonC,DetraitM,DalleJH,MichelG,DhédinN,ChalandonY,etal.Improved out come in children compared
  24. to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia:
  25. a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-
  26. TC).JCancerResClinOncol.2022;148(8):2083‑97.
  27. AntierC,JullienM,TessoulinB,LoiratM,PeterlinP,GarnierA,etal.Late Relapse after Allogeneic Stem Cell
  28. Transplantation in Patients Treated for Acute Myeloid Leukemia : Relapse Incidence,Characteristics, Role of
  29. Conditioning Regimen, and Outcome. Cancers.2024;16(7):1419.
  30. BejanyanN,WeisdorfDJ,LoganBR,WangHL,DevineSM,deLimaM,etal. Survival of AML patients
  31. relapsing after allogeneic hematopoietic cell transplantation : a CIBMTR study.Biol Blood Marrow TransplantJ
  32. Am Soc Blood Marrow Transplant.2015;21(3):454‑9.
  33. CopelanEA,HamiltonBK,AvalosB,AhnKW,BolwellBJ,ZhuX,etal.Better leukemia-free and overall
  34. survival in AML in first remission following cyclophosphamide in combination with busulfan compared with
  35. TBI.Blood.2013;122(24):3863‑70.
  36. IshidaH,KatoM,KudoK,TagaT,TomizawaD,MiyamuraT,etal.Comparison of Outcomes for Pediatric
  37. Patients With Acute Myeloid Leukemia in Remission and Under going Allogeneic Hematopoietic Cell
  38. Transplantation With Myeloablative Conditioning Regimens Basedon Either Intravenous Busulfanor Total Body
  39. Irradiation:A Report From the Japanese Society for Hematopoietic Cell Transplantation .Biol Blood Marrow
  40. Transplant JAm Soc Blood Marrow Transplant.2015;21(12):2141‑7.
  41. LucasAGT,BhoopalanSV,NierkensS,deKoningC,KeerthiD,SeetharamanA,etal.Real World Use of the
  42. Pediatric Disease Risk Index for Allogeneic Hematopoietic Cell Transplantation in Patients with Acute
  43. Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Multicenter Study.Transplant Cell Ther.2024;30(2,
  44. Supplement):S107‑8.
  45. AroraS,PushpamD,TiwariA,ChoudharyP,ChopraA,GuptaR,etal.Allogeneic hematopoietic stem cell
  46. transplantin pediatric acute myeloid leukemia : Lessons learnt from atertiaryc are centerin India.Pediatr
  47. Transplant.2021;25(3):e13918.
  48. VersluysAB,BoelensJJ,PronkC,LankesterA,BordonV,BuechnerJ,etal.Hematopoietic cell transplantin
  49. pediatric acute myeloid leukemia after similar up front therapy; acomparison of condition ingregimens.Bone
  50. MarrowTransplant.2021;56(6):1426‑32.
  51. RakhmanovaZ,PainaO,BarkhatovI,SadykovA,RazumovaS,TsvetkovaL,etal.Molecular genetic and
  52. cytofluorimetric prognostic factors in the development of acute myeloid leukemia relapse in children after
  53. allogeneic hematopoietic stem cell transplantation. Pediatr Hematol Immunopathol.2023;22:24‑30.
  54. GrochowLB,JonesRJ,BrundrettRB,BraineHG,ChenTL,SaralR,etal.Pharma cokineticsofbusulfan:
  55. correlation with veno-occlusive disease in patients undergoing bone marrow transplantation.Cancer Chemother
  56. Pharmacol(1989)25:55-61.
  57. KalwakK,MielcarekM,PatrickK,StyczynskiJ,BaderP,CorbaciogluS,etal.Treosulfan-fludarabine-thiotepa-
  58. based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with
  59. hematological malignancies.Bone Marrow Transplant.2020;55(10):1996‑2007.
  60. RehmanMEU,KhansuhebM,UmarH,FarheenNaazF,ShahZ,KhanZ,etal.Busulfanversustreosulfan
  61. conditioning for acute myeloid leukemia and myelodysplastic syndrome:A systematic reviewand meta-analysis.
  62. JClinOncol.2023;41(16_suppl):e19032‑e19032.
  63. SantosGW,TutschkaPJ,BrookmeyerR,SaralR,BeschornerWE,BiasWB,etal.Marrow transplantation for
  64. acute non lymphocytic leukemia after treatment with busulfanandcyclophosphamide.NEnglJMed.
  65. ;309(22):1347‑53.
  66. MichelG,GluckmanE,Esperou-BourdeauH,ReiffersJ,PicoJL,BordigoniP,etal.Allogeneic bone marrow
  67. transplantation for children with acute myeloblastic leukemia in first complete remission:impact of conditioning
  68. regimen without total-body irradiation--areport from the Société Française de Greffe de Moelle.JClinOncol
  69. OffJAmSocClin Oncol.1994;12(6):1217‑22.
  70. BartelinkIH, ReijEMLvan,GerhardtCE,MaarseveenEM van,WildtAde, Versluys B,etal. Fludarabineand
  71. Exposure-TargetedBusulfanCompares Favorably with Busulfan/Cyclophosphamide-BasedRegimensin
  72. Pediatric Hematopoietic Cell Transplantation : Maintaining Efficacy with Less Toxicity.Biol Blood Marrow
  73. Transplant.2014;20(3):345‑53.
  74. BartelinkIH,BrediusRGM,BelitserSV,SuttorpMM,BieringsM,KnibbeCAJ,etal.Association between
  75. Busulfan Exposure and Outcome in Children Receiving Intravenous Busulfanbefore Hematologic Stem Cell
  76. Transplantation.Biol Blood Marrow Transplant.2009;15(2):231‑41.
  77. BartelinkIH,LalmohamedA,vanReijEML,DvorakCC,SavicRM,ZwavelingJ,etal.ANew Harmonized
  78. Approach to Estimate Busulfan Exposure Predicts Survivaland Toxicity after Hematopoietic Cell Transplantation
  79. in Children and Young Adults :a Multicenter Retrospective Cohort Analysis .Lancet Haematol.
  80. ;3(11):e526‑36.
  81. YanivI,KraussAC,BeohouE,DalissierA,CorbaciogluS,ZeccaM,etal.Second Hematopoietic Stem Cell
  82. Transplantation forPost-Transplantation Relapsed Acute Leukemia in Children : A Retrospective EBMT-PDWP
  83. Study.Biol Blood Marrow Transplant.2018;24(8):1629‑42.
  84. UdenT,BertainaA,AbrahamssonJ,AnsariM,BalduzziA,BourquinJP,etal.Outcome of children relapsing
  85. after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: aretrospectiveI-BFM
  86. analysis of 333 children.BrJHaematol.2020;189(4):745‑50.
  87. SchmidC,LabopinM,NaglerA,BornhäuserM,FinkeJ,FassasA,etal.Donor lymphocyte in fusion in the
  88. treatment offirst hematologicalr elapse after allogeneic stem-cell transplantation in adults with acute myeloid
  89. leukemia: are trospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia
  90. Working Party.JClin Oncol Off JAm Soc Clin Oncol.2007;25(31):4938‑45.
  91. KolbHJ,SchattenbergA,GoldmanJM,HertensteinB,JacobsenN,ArceseW,etal.Graft-Versus-Leukemia
  92. Effect of Donor Lymphocyte Transfusions in Marrow Grafted Patients.Blood.1995;86(5):2041‑50.
  93. CzogałaM,CzogałaW,Pawińska-WąsikowskaK,KsiążekT,Bukowska-StrakovaK,Sikorska-FicB,etal.
  94. Characteristics and Outcome ofFLT3-ITD-Positive Pediatric Acute Myeloid Leukemia—Experience of Polish
  95. Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022. Cancers.2023;15(18):4557.
  96. BuldiniB,Maurer-GranofszkyM,VarottoEandDworzakMN.Flow-Cytometric Monitoring of Minimal
  97. Residual Disease in Pediatric Patients With Acute Myeloid Leukemia :Recent Advances and Future Strategies.
  98. Front.Pediatr.2019;7:412.