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Transplant Outcomes

Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Bone Marrow Transplantation volume 49, pages 382–388 (2014)Cite this article

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Abstract

Allogeneic hematopoietic SCT (HSCT) appears to be an efficient tool to cure high-risk AML in first CR but the choice between BU-based or TBI-based conditioning regimens still remains controversial. In order to analyze the impact of conditioning regimen on long-term survival, we conducted a retrospective analysis from French registry data including all consecutive patients under 18 years old (n=226) from 1980 to 2004 transplanted for AML in CR1 from sibling (n=142) or matched unrelated donors and given either TBI-1200 cGy and CY 120 mg/kg (TBI-Cy, n=84) or BU 16 mg/kg and CY 200 mg/kg (BuCy200, n=142). Patient subgroups were comparable for all criteria except for median age at diagnosis and HSCT and for donor type. Both 5-year OS and disease-free survival (DFS) were significantly better in BuCy200 group (P=0.02 and 0.005, respectively). In multivariate analysis, both HLA matching and BuCy200 appeared as good prognostic factors for treatment-related mortality and DFS. Grade 2–4 acute GvHD and chronic GvHD rates were statistically higher in TBI-Cy group than in Bu-Cy200 one with a RR at 2 (P=0.002). In total, Bu-Cy200 conditioning regimen gives better outcome compared with TBI-Cy irrespective of the stem cell source and the donor type.

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References

  1. Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y et al. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia 2005; 19: 2072–2081.

    Article  CAS  Google Scholar 

  2. Perel Y, Auvrignon A, Leblanc T, Michel G, Reguerre Y, Vannier JP et al. Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit—multicenter studies of the French LAME (Leucemie Aigue Myeloblastique Enfant) Cooperative Group. Leukemia 2005; 19: 2082–2089.

    Article  CAS  Google Scholar 

  3. Perel Y, Auvrignon A, Leblanc T, Vannier JP, Michel G, Nelken B et al. Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucamie Aique Myeloide Enfant. J Clin Oncol 2002; 20: 2774–2782.

    Article  Google Scholar 

  4. Vettenranta K . Current European practice in pediatric myeloablative conditioning. Bone Marrow Transplant 2008; 41 (Suppl 2): S14–S17.

    Article  Google Scholar 

  5. Michel G, Gluckman E, Esperou-Bourdeau H, Reiffers J, Pico JL, Bordigoni P et al. Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation—a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol 1994; 12: 1217–1222.

    Article  CAS  Google Scholar 

  6. Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009; 114: 2489–2496.

    Article  CAS  Google Scholar 

  7. Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 2010; 28: 2674–2681.

    Article  Google Scholar 

  8. Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 2009; 113: 6558–6566.

    Article  CAS  Google Scholar 

  9. Meshinchi S, Alonzo TA, Stirewalt DL, Zwaan M, Zimmerman M, Reinhardt D et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006; 108: 3654–3661.

    Article  CAS  Google Scholar 

  10. Meshinchi S, Arceci RJ, Sanders JE, Smith FO, Woods WB, Radich JP et al. Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood 2006; 108: 400–401.

    Article  CAS  Google Scholar 

  11. von Neuhoff C, Reinhardt D, Sander A, Zimmermann M, Bradtke J, Betts DR et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol 2010; 28: 2682–2689.

    Article  CAS  Google Scholar 

  12. Burke MJ, Wagner JE, Cao Q, Ustun C, Verneris MR . Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia. Biol Blood Marrow Transplant 2013; 19: 1021–1025.

    Article  Google Scholar 

  13. Gassas A, Ishaqi MK, Afzal S, Finkelstein-Shechter T, Dupuis A, Doyle J . A comparison of the outcomes of children with acute myelogenous leukemia in either first or second complete remission (CR1 vs CR2) following allogeneic hematopoietic stem cell transplantation at a single transplant center. Bone Marrow Transplant 2008; 41: 941–945.

    Article  CAS  Google Scholar 

  14. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998; 92: 2322–2333.

    CAS  PubMed  Google Scholar 

  15. Leblanc T, Le Coniat M, Flexor M, Baruchel A, Daniel MT, Berger R . An interstitial 11q23 deletion proven to be a rearrangement interrupting the MLL gene in an infant with acute myeloblastic leukemia. Leukemia 1996; 10: 1844–1846.

    CAS  PubMed  Google Scholar 

  16. Belkacemi Y, Rio B, Touboul E . Total body irradiation: techniques, dosimetry, and complications. Cancer Radiother 1999; 3: 162–173.

    Article  CAS  Google Scholar 

  17. Vassal G, Michel G, Esperou H, Gentet JC, Valteau-Couanet D, Doz F et al. Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemother Pharmacol 2008; 61: 113–123.

    Article  CAS  Google Scholar 

  18. Labopin M, Iacobelli S . Statistical guidelines for EBMT. 2003 Available at http://portal.ebmt.org/sites/clint2/clint/Documents/StatGuidelines_oct2003.pdf.

  19. Klingebiel T, Reinhardt D, Bader P . Place of HSCT in treatment of childhood AML. Bone Marrow Transplant 2008; 42 (Suppl 2): S7–S9.

    Article  CAS  Google Scholar 

  20. Oliansky DM, Rizzo JD, Aplan PD, Arceci RJ, Leone L, Ravindranath Y et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant 2007; 13: 1–25.

    Article  Google Scholar 

  21. Niewerth D, Creutzig U, Bierings MB, Kaspers GJ . A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood 2010; 116: 2205–2214.

    Article  CAS  Google Scholar 

  22. Sisler IY, Koehler E, Koyama T, Domm JA, Ryan R, Levine JE et al. Impact of conditioning regimen in allogeneic hematopoetic stem cell transplantation for children with acute myelogenous leukemia beyond first complete remission: a pediatric blood and marrow transplant consortium (PBMTC) study. Biol Blood Marrow Transplant 2009; 15: 1620–1627.

    Article  Google Scholar 

  23. Slattery JT, Sanders JE, Buckner CD, Schaffer RL, Lambert KW, Langer FP et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant 1995; 16: 31–42.

    CAS  PubMed  Google Scholar 

  24. Ljungman P, Hassan M, Bekassy AN, Ringden O, Oberg G . High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients. Bone Marrow Transplant 1997; 20: 909–913.

    Article  CAS  Google Scholar 

  25. Shi-Xia X, Xian-Hua T, Hai-Qin X, Bo F, Xiang-Feng T . Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis. Leuk Lymphoma 2010; 51: 50–60.

    Article  Google Scholar 

  26. Ferry C, Socie G . Busulfan-cyclophosphamide versus total body irradiation-cyclophosphamide as preparative regimen before allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia: what have we learned? Exp Hematol 2003; 31: 1182–1186.

    Article  CAS  Google Scholar 

  27. Shenoy S, Smith FO . Hematopoietic stem cell transplantation for childhood malignancies of myeloid origin. Bone Marrow Transplant 2008; 41: 141–148.

    Article  CAS  Google Scholar 

  28. Willemze AJ, Geskus RB, Noordijk EM, Kal HB, Egeler RM, Vossen JM . HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI. Bone Marrow Transplant 2007; 40: 319–327.

    Article  CAS  Google Scholar 

  29. Mengarelli A, Iori A, Guglielmi C, Romano A, Cerretti R, Torromeo C et al. Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia. Haematologica 2002; 87: 52–58.

    CAS  PubMed  Google Scholar 

  30. Tutschka PJ, Copelan EA, Klein JP . Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987; 70: 1382–1388.

    CAS  PubMed  Google Scholar 

  31. Michel G, Socie G, Gebhard F, Bernaudin F, Thuret I, Vannier JP et al. Late effects of allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: the impact of conditioning regimen without total-body irradiation—a report from the Societe Francaise de Greffe de Moelle. J Clin O 1997; 15: 2238–2246.

    Article  CAS  Google Scholar 

  32. Petropoulos D, Worth LL, Mullen CA, Madden R, Mahajan A, Choroszy M et al. Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies. Bone Marrow Transplant 2006; 37: 463–467.

    Article  CAS  Google Scholar 

  33. Socie G, Clift RA, Blaise D, Devergie A, Ringden O, Martin PJ et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies. Blood 2001; 98: 3569–3574.

    Article  CAS  Google Scholar 

  34. Oudin C, Simeoni MC, Sirvent N, Contet A, Begu-Le Coroller A, Bordigoni P et al. Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 2011; 117: 4442–4448.

    Article  CAS  Google Scholar 

  35. Inagaki J, Nagatoshi Y, Sakiyama M, Nomura Y, Teranishi H, Sasaki T et al. TBI and melphalan followed by allogeneic hematopoietic SCT in children with advanced hematological malignancies. Bone Marrow Transplant 2011; 46: 1057–1062.

    Article  CAS  Google Scholar 

  36. Kroger N, Zabelina T, Sonnenberg S, Kruger W, Renges H, Stute N et al. Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia. Bone Marrow Transplant 2000; 26: 711–716.

    Article  CAS  Google Scholar 

  37. Worth L, Tran H, Petropoulos D, Culbert S, Mullen C, Roberts W et al. Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide. Bone Marrow Transplant 1999; 24: 947–952.

    Article  CAS  Google Scholar 

  38. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 2859–2867.

    Article  Google Scholar 

  39. Mohty M, de Lavallade H, Ladaique P, Faucher C, Vey N, Coso D et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia 2005; 19: 916–920.

    Article  CAS  Google Scholar 

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Acknowledgements

Authors acknowledge Nicole Raus, the data manager of Société Francaise de Greffe de Moelle et de Thérapie Cellulaire for her support and excellent work.

Author Contribution

J-HD and EdB designed the study. J-HD chaired the study; EdB, AP, CG, YB, AS, FR, P-SR, J-PV, PL, KY, GM and J-HD recruited the patients; J-HD, EdB, AC and AD analyzed the study data and all authors critically reviewed the manuscript.

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Authors and Affiliations

  1. Pediatric Hematology Department, Jeanne de Flandre Hospital, CHRU Lille, Lille, France

    E de Berranger & B Bruno

  2. EA 2694, Faculté de Médecine, Lille, France

    A Cousien & A Duhamel

  3. Pediatric Hematology and Oncology Department, Trousseau Hospital, Assistance Publique—Hopitaux de Paris, Paris, France

    A Petit

  4. Hematology Department, Saint-Louis Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France

    R Peffault de Latour

  5. Pediatric Hematology Department, Timone Hospital, Marseille, France

    C Galambrun & G Michel

  6. Pediatric Hematology and Oncology Unit, IHOP, Lyon, France

    Y Bertrand

  7. Pediatric Hematology and Oncology Department, CHU Nancy, Vandoeuvre-les-Nancy, France

    A Salmon

  8. Centre Hospitalier et Universitaire (CHU) de Nantes, Service d'Onco-Hématologie Pédiatrique, Nantes, France

    F Rialland

  9. Université de Nantes, Faculté de Médecine, Nantes, France

    F Rialland

  10. HSCT department, CHU Besançon, Besançon, France

    P-S Rohrlich

  11. Pediatric Hematology and Oncology Unit, CHU Rouen, Rouen, France

    J-P Vannier

  12. Pediatric Hematology and Oncology Unit, CHU Strasbourg, Strasbourg, France

    P Lutz

  13. Pediatric Hematology Department, Robert Debré Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France

    K Yakouben & J-H Dalle

  14. INSERM 1149, Paris Diderot University, Paris, France

    J-H Dalle

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  1. E de Berranger
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Correspondence to J-H Dalle.

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de Berranger, E., Cousien, A., Petit, A. et al. Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Bone Marrow Transplant 49, 382–388 (2014). https://doi.org/10.1038/bmt.2013.185

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