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

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. Access through your institution Buy or

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ALLOGENEIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) IN SECOND COMPLETE REMISSION (CR2) TRANSPLANTED FROM UNRELATED DONORS WITH POST-TRANSPLANT

CYCLOPHOSPHAMIDE (PTCY). A STUDY ON BEHALF OF THE ACUTE LEUKEMIA WORKING PARTY OF THE EUROPEAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION Article 23 February 2023 HEMATOPOIETIC CELL

TRANSPLANT IN PEDIATRIC ACUTE MYELOID LEUKEMIA AFTER SIMILAR UPFRONT THERAPY; A COMPARISON OF CONDITIONING REGIMENS Article 19 January 2021 REDUCED INTENSITY VERSUS NON-MYELOABLATIVE

CONDITIONING REGIMEN FOR HAPLOIDENTICAL TRANSPLANTATION AND POST-TRANSPLANTATION CYCLOPHOSPHAMIDE IN COMPLETE REMISSION ACUTE MYELOID LEUKEMIA: A STUDY FROM THE ALWP OF THE EBMT Article 25

June 2022 REFERENCES * 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  * 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  * 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  *

Vettenranta K . Current European practice in pediatric myeloablative conditioning. _Bone Marrow Transplant_ 2008; 41 (Suppl 2): S14–S17. Article  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Belkacemi

Y, Rio B, Touboul E . Total body irradiation: techniques, dosimetry, and complications. _Cancer Radiother_ 1999; 3: 162–173. Article  CAS  Google Scholar  * 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  * Labopin M, Iacobelli S . Statistical guidelines for EBMT. 2003 Available at

http://portal.ebmt.org/sites/clint2/clint/Documents/StatGuidelines_oct2003.pdf. * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  Download references 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.

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Pediatric Hematology Department, Jeanne de Flandre Hospital, CHRU Lille, Lille, France E de Berranger & B Bruno * EA 2694, Faculté de

Médecine, Lille, France A Cousien & A Duhamel * Pediatric Hematology and Oncology Department, Trousseau Hospital, Assistance Publique—Hopitaux de Paris, Paris, France A Petit *

Hematology Department, Saint-Louis Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France R Peffault de Latour * Pediatric Hematology Department, Timone Hospital, Marseille, France C

Galambrun & G Michel * Pediatric Hematology and Oncology Unit, IHOP, Lyon, France Y Bertrand * Pediatric Hematology and Oncology Department, CHU Nancy, Vandoeuvre-les-Nancy, France A

Salmon * Centre Hospitalier et Universitaire (CHU) de Nantes, Service d'Onco-Hématologie Pédiatrique, Nantes, France F Rialland * Université de Nantes, Faculté de Médecine, Nantes,

France F Rialland * HSCT department, CHU Besançon, Besançon, France P-S Rohrlich * Pediatric Hematology and Oncology Unit, CHU Rouen, Rouen, France J-P Vannier * Pediatric Hematology and

Oncology Unit, CHU Strasbourg, Strasbourg, France P Lutz * Pediatric Hematology Department, Robert Debré Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France K Yakouben & J-H

Dalle * INSERM 1149, Paris Diderot University, Paris, France J-H Dalle Authors * E de Berranger View author publications You can also search for this author inPubMed Google Scholar * A

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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 Download citation * Received: 25 January 2013 *

Revised: 11 September 2013 * Accepted: 14 September 2013 * Published: 09 December 2013 * Issue Date: March 2014 * DOI: https://doi.org/10.1038/bmt.2013.185 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative KEYWORDS * AML * children * overall * conditioning * transplantation