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Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation.
Biol Blood Marrow Transplant. 2017 Mar; 23(3):467-474.BB

Abstract

Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS.

Authors+Show Affiliations

Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom. Electronic address: Giovanna.Lucchini@gosh.nhs.uk.BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.BMT Statistical Unit, European Group for Blood and Marrow Transplantation Office, Universite' Pierre et Marie Curie, Paris, France.Hemato-immunology Department, Hôpital Robert Debre, Paris, France.Paediatric Haematology/Oncology Department, Bristol Royal Hospital for Children, Bristol, United Kingdom.Pediatric Hematology-Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom.Haematology Department, Royal Hospital for Sick Children, Glasgow, United Kingdom.Pediatric Hematology-Oncology Department, IRCCS Bambino Gesu' Children Hospital, Rome, Italy.Pediatric Hematology and Oncology Department, Institut d'Hématologie et d'Oncologie Pédiatriqu, Lyon, France.Bone Marrow and Stem Cell Transplantation Department, King Hussein Cancer Centre, Amman, Jordan.Hematology/Transplantation Department, Hôpital St. Louis, Paris, France.Hematology/Immunology/SCT Department, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.Pediatrics Department, Division of Immuno-Hematology and Stem Cell Transplantation Leiden University Hospital, The Netherlands.Paediatric Haematology & Oncology Department, University Hospital Motol, Prague, Czech Republic.Hematology Department, Centre Pierre et Marie Curie, Alger, Algeria.Paediatrics and Adolescent Medicine Department, Rigshospitalet, Copenhagen, Denmark.Hematology and Transplantology Department, Saint Petersburg State Medical Pavlov University, Ratsa Gorbacheva Memorial Children's Institute, St. Petersburg, Russia.Stem Cell Transplantation Department, University College Hospital, London, United Kingdom.Stem Cell Transplantation Department, St. Anna Kinderspital, Vienna, Austria.Stem Cell Transplantation and Immunology Department, Universitätsklinikum Frankfurt, Goethe-Universität, Frankfurt am Main, Germany.Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

27916512

Citation

Lucchini, Giovanna, et al. "Impact of Conditioning Regimen On Outcomes for Children With Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. an Analysis On Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 23, no. 3, 2017, pp. 467-474.
Lucchini G, Labopin M, Beohou E, et al. Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2017;23(3):467-474.
Lucchini, G., Labopin, M., Beohou, E., Dalissier, A., Dalle, J. H., Cornish, J., Zecca, M., Samarasinghe, S., Gibson, B., Locatelli, F., Bertrand, Y., Abdel-Rahman, F., Socie, G., Sundin, M., Lankester, A., Sedlacek, P., Hamladji, R. M., Heilmann, C., Afanasyev, B., ... Veys, P. (2017). Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 23(3), 467-474. https://doi.org/10.1016/j.bbmt.2016.11.022
Lucchini G, et al. Impact of Conditioning Regimen On Outcomes for Children With Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. an Analysis On Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2017;23(3):467-474. PubMed PMID: 27916512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation. AU - Lucchini,Giovanna, AU - Labopin,Myriam, AU - Beohou,Eric, AU - Dalissier,Arnauld, AU - Dalle,Jean Hughes, AU - Cornish,Jacqueline, AU - Zecca,Marco, AU - Samarasinghe,Sujith, AU - Gibson,Brenda, AU - Locatelli,Franco, AU - Bertrand,Yves, AU - Abdel-Rahman,Fawzi, AU - Socie,Gerald, AU - Sundin,Mikael, AU - Lankester,Arjan, AU - Sedlacek,Peter, AU - Hamladji,Rose Marie, AU - Heilmann,Carsten, AU - Afanasyev,Boris, AU - Hough,Rachel, AU - Peters,Cristina, AU - Bader,Peter, AU - Veys,Paul, Y1 - 2016/12/01/ PY - 2016/10/21/received PY - 2016/11/29/accepted PY - 2016/12/6/pubmed PY - 2018/3/1/medline PY - 2016/12/6/entrez SP - 467 EP - 474 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 23 IS - 3 N2 - Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/27916512/Impact_of_Conditioning_Regimen_on_Outcomes_for_Children_with_Acute_Myeloid_Leukemia_Undergoing_Transplantation_in_First_Complete_Remission__An_Analysis_on_Behalf_of_the_Pediatric_Disease_Working_Party_of_the_European_Group_for_Blood_and_Marrow_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(16)30522-5 DB - PRIME DP - Unbound Medicine ER -