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Kongressberichte 2019
45th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT)
Oral Session 9: Late-breaking abstracts
OS9-2 - MYELOABLATIVE CONDITIONING FOR FIRST ALLOGENEIC HSCT IN PEDIATRIC ALL: FTBI OR CHEMOTHERAPY? - AN UPDATE OF THE RETROSPECTIVE MULTICENTER EBMT-PDWP STUDY
1Goethe University Frankfurt, Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, Frankfurt am Main, Germany, 2St Anna Children’s Hospital, Department for Stem Cell Transplantation, Vienna, Austria, 3University Hospital Motol, Prague, Department of Pediatric Hematology and Oncology, Prague, Czech Republic, 4Hôpital Robert Debré and Paris-Diderot University, Department of Pediatric Hemato-Immunology, Paris, France, 5Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Stem Cell Transplant Unit, Athens, Greece, 6School of Medicine, Bahcesehir University, Department of Pediatric Hematology-Oncology, Istanbul, Turkey, 7University of Medical Sciences, Department and Clinic of Pediatric Oncology, Hematology and Transplantology, Poznan, Poland, 8Leiden University Medical Center, Department of Pediatrics, Leiden, Netherlands, 9University of Bologna, Hematology-Oncology Unit 'Lalla Seràgnoli', Department of Pediatrics, Bologna, Italy, 10Tehran University of Medical Sciences, Hematology-Oncology and Stem Cell Transplantation Research Center, Teheran, Iran, Islamic Republic of, 11Copenhagen University Hospital, Rigshospitalet, Department of Pediatrics, Copenhagen, Denmark, 12Oslo University Hospital Rikshospitalet, Department of Pediatric Medicine, Oslo, Norway, 13United St. Istvan and St. László Hospital, Department of Paediatric Haematology and Stem Cell Transplantation, Budapest, Hungary, 14Service Hématologie Greffe de Moelle, Centre Pierre et Marie Curie, Alger, Algeria, 15Hospital Universitario Vall d'Hebron, Servicio de Hematologia y Oncologia Pediátricas, Barcelona, Spain, 16Russian Children's Hospital, BMT Department, Moscow, Russian Federation, 17Timone Enfants Hospital, AP-HM and Aix-Marseille University, Department of Pediatric Hematology and Oncology and Research Unit EA 3279, Marseille, France, 18IRCCS Ospedale Pediatrico Bambino Gesù, Università di Pavia, Dipartimento di Onco-Ematologia Pediatrica e Medicina Trasfusionale, Rome, Italy, 19Stanford University Medical Center, Diviosin of Stem Cell and Regenerative Medicine, Stanford, CA, United States, 20NHS Foundation Trust, Great Ormond Street Hospital for Children, London, United Kingdom, 21Cliniques Universitaires Saint-Luc, Department of Pediatric Hematology and Oncology, Brussels, Belgium, 22Hadassah-Hebrew University Medical Center, Department of Bone Marrow Transplantation, Jerusalem, Israel, 23University Children's Hospital, Division of Stem Cell Transplantation, Children`s Research Center (CRC), Zurich, Switzerland, 24Republic Clinical Research Centre, Pediatric Oncology and Hematology, Minsk, Belarus, 25Comenius University Medical School, Limbová, BMT Unit, Department of Pediatric Hematology and Oncology, Bratislava, Slovakia, 26Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Pediatric Blood Disorders, Immunodeficiency and Stem Cell Transplantation, Stockholm, Sweden, 27Affiliate of Vilnius University Hospital Santariskiu Klinikos, Center of Pediatric Oncology and Hematology, Bone Marrow Transplantation Unit, Children's Hospital, Vilnius, Lithuania, 28Tartu University Hospital, Department of Pediatric Hematology and Oncology, Tartu, Estonia, 29University Hospital Centre, Department of Haematology, Internal Clinic, Zagreb, Croatia, 30Regina Margherita Children's Hospital, Paediatric Onco-Haematology, City of Science and Health of Turin, Turino, Italy, 31Nicolaus Copernicus University Torun, Department of Pediatric Hematology and Oncology, Collegium Medicum, Bydgoszcz, Poland, 32University Medical Centre Utrecht Pediatrics, BMT-Unit, Urecht, Netherlands, 33Child Welfare Center, Borsod County Teaching Hospital, Department of Hematology, Miskolc, Hungary, 34Instituto Portugues Oncologia, Bone Marrow Transplant Program, Lisboa, Portugal, 35Saint Petersburg State Medical I.P. Pavlov University, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Haematology and Transplantation, Saint Petersburg, Russian Federation, 36Geneva University Hospital, Department of Pediatrics, Onco-Hematology Unit, Geneva, Switzerland, 37University of Helsinki, Hospital for Children and Adolescents, Helsinki, Finland, 38King Faisal Specialist Hospital & Research Center, Department of Pediatric Hematology Oncology, Riyadh, Saudi Arabia, 39Wroclaw Medical University, Department of Bone Marrow Transplantation, Oncology and Hematology, Cape of Hope Medical Center, Wroclaw, Poland, 40NHS Foundation Trust, University Hospitals Bristol, Bristol, United Kingdom, 41IHOP and Claude Bernard University, Department of Pediatric Hematology and BMT, Lyon, France, 42Akdeniz University, Department of Pediatric Hematology-Oncology, School of Medicine, Antalya, Turkey, 43Shariati Hospital, Hematology-Oncology and BMT Research, Teheran, Iran, Islamic Republic of, 44Portuguese Institute of Oncology, Bone Marrow Transplantation Service, Porto, Portugal, 45EBMT Paediatric Diseases Working Party, Paris, France, 46EBMT Paris Study Office, Paris, France, 47University of Regensburg, Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Regensburg, Germany
Background: It is still a matter-of-debate if chemotherapy (CHT) can replace fractionated total-body-irradiation (fTBI) in myeloablative conditioning (MAC) for allo-HSCT in pediatric ALL. We hereby present the latest update of this international multicenter EBMT-PDWP-study (Blood 2017, 130(Suppl. 1):911).
Methods: This update was done to extend the time of follow-up (FU, date of analysis: 01/OCT/2018). To compare outcomes of fTBI vs CHT-conditioning, we performed a retrospective EBMT-registry study. Children aged 2-18 years (y) after MAC for first allo-HSCT of BM/PBSC from MSD/UD in CR1/CR2 between 2000-2012 were included. Propensity-score-weighting was used to control pretreatment imbalances of observed variables. This statistical method ensured that analyzed groups differed only in the parameter under investigation (here: conditioning).
Results: In total 3054 pts (CR1: 1498 (49%), CR2: 1556 (51%)) were included. CR1: 1041 pts (69%) received BM and 457 pts (31%) PBSC from MSD (756 (50%)) or UD (742 (50%)). CR2: 1064 pts (68%) received BM and 492 pts (32%) PBSC from MSD (672 (43%)) or UD (884 (57%)). Overall, conditioning was fTBI- in 2630 (86%) and CHT-based in 424 pts (14%). Busulfan/Cyclophosphamide/Etoposide (Bu/Cy/Eto) was the most frequently applied CHT-regimen in CR1 (66 (31%)) and Bu/Cy in CR2 (68 (32%)). The remaining conditionings included 5 combinations (other-chemo).
1498 pts in CR1 were conditioned with fTBI (1285), Bu/Cy/Eto (66) or other-chemo (147) with median-FU of 6.9, 6.2 and 4.5 y. In weighted univariate analysis, 5-y-OS was 68.8% after fTBI, 75.6% after other-chemo and 81.4% after Bu/Cy/Eto. In weighted Cox-model, taking into account the center-effect, pts having received Bu/Cy/Eto had a lower risk to experience an event compared to fTBI (HR=0.53, P=.029). 5-y-LFS (range: 58.4% (other-chemo) to 72.6% (Bu/Cy/Eto)), 5-y-RI (range: 17.1% (Bu/Cy/Eto) to 31.8% (other-chemo)) and 5-y-NRM (range: 9.8% (other-chemo) to 13.8% (fTBI)) did not show significant differences in weighted Cox-model.
1556 pts in CR2 were conditioned with fTBI (1345), Bu/Cy (68) or other-chemo (143) with median-FU of 6.2, 5.2 and 5.8 y. In weighted univariate analysis, 5-y-OS was 31.1% after other-chemo, 43.5% after Bu/Cy and 58.8% after fTBI. In weighted Cox-model, pts having received other-chemo had a higher risk to experience an event compared to fTBI (HR=2.00, P=< .0001). 5-y-LFS was 25.2% after other-chemo, 32.4% after Bu/Cy and 53.7% after fTBI. In weighted Cox-model, children having received Bu/Cy and other-chemo had a higher risk to experience an event compared to fTBI (HR=1.78, P=.005; HR=1.92, P< .0001). 5-y-RI was 30.6% after fTBI, 49.3% after BuCy and 53.7% after other-chemo. In weighted Cox-model, pts having received Bu/Cy and other-chemo had a higher risk to experience an event compared to fTBI (HR=2.06, P=.006; HR=2.13, P< .0001). 5-y-NRM (range: 18.3% (BuCy) to 21.1% (other-chemo)) did not show significant differences in weighted Cox-model.
Conclusions: This recent study-update ensured a substantial FU. We confirmed the clear superiority of fTBI-conditioning compared to CHT with regard of LFS and RI for ALL-pts undergoing allo-HSCT in CR2. For pts in CR1 we could not find significant differences between fTBI and CHT-conditioning. These retrospective findings are currently re-evaluated in the prospective, randomized, international trial (ALL-SCTped-2012-FORUM).
Disclosure: Nothing to declare.