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2862 Outcome of Allogeneic HSCT after Chemo-Based Conditioning in Infants with Acute Myeloid Leukemia in First Complete Remission: A Multicenter EBMT-PDWP Study

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological, AML, Clinical Research, Clinically Relevant, Diseases, Pediatric, Real World Evidence, Therapies, Registries, Myeloid Malignancies, Study Population, Transplantation, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Andre Manfred Willasch, MD 1*, Christina Peters2*, Adriana Balduzzi, MD3, Jean-Hugues Dalle4*, Marco Zecca5*, Amal Al-Seraihy, MD6*, Franco Locatelli, MD, PhD7, Yves Bertrand, MD, PhD8*, Stephen Robinson9*, Tracey OBrien10*, Amos Toren, MD Phd11*, Dragana S. Vujic12*, Jacques-Olivier Bay, MD, PhD13, Charlotte Jubert14*, Maura Faraci15*, Fanny Rialland, MD16*, Vassiliki Kitra-Roussou, MD17*, Gerard Michel, MD18*, Mariacristina Menconi, MD19*, Franca Fagioli, MD20*, Ottavio Ziino, MD21*, Mikael Sundin, MD, PhD22, Cecile Pochon, MD23*, Paul Veys24*, Jose Maria Moraleda, MD, PhD25*, Alessandra Biffi, MD26*, Arnaud Dalissier, PhD27*, Selim Corbacioglu28, Maud Ngoya29*, Jacques-Emmanuel Galimard29* and Peter Bader1

1Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany
2St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria
3Bone Marrow Transplantation Unit, Clinica Pediatrica Università degli Studi di Milano-Bicocca, Fondazione MBBM, Monza, Italy
4Department of Pediatric Hemato-Immunology, Hôpital Robert Debré and Université de Paris, Paris, France
5Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
6Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
7Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
8Department of Pediatric Hematology and BMT, IHOP and Claude Bernard University, Lyon, France
9University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
10Transplant and Cellular Therapies Program, Kids Cancer Centre, Sydney Children's Hospital, Sydney, Australia
11Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Aviv, Israel
12Mother and Child Health Care Institute of Serbia "Dr Vukan Čupić", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
13CHU de Clermont-Ferrand, Site Estaing, Service de thérapie cellulaire et d'hématologie clinique adulte, Clermont-Ferrand, France
14Department of Pediatric Hematology, Bordeaux Hospital, Bordeaux, France
15Department of Hematology-Oncology, Hematopoietic Stem Cell Transplant Unit, Hematology-Oncology, IRCSS, Istituto G. Gaslini, Genova, Italy
16Department of Pediatric Hematology and BMT, Nantes University Hospital, Nantes, France
17Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece
18Department of Pediatric Hematology and Oncology and Research Unit, Timone Enfants Hospital, AP-HM and Aix-Marseille University, Marseille, France
19Hematopoietic Stem Cell Transplant Unit, Paediatric Hematology-Oncology, Azienda Ospedaliera Universitaria Pisa, Pisa, Italy
20The Division of Pediatric Onco-Hematology, Ospedale Regina Margherita Centro, Torino, Italy
21Pediatric Hematology and Oncology, Department of Pediatric Haemato-Oncology, ARNAS Civico e Di Cristina, Palermo, Italy
22Division Pediatric Hematology, Immunology and HCT, Pediatric Hematology, Immunology and HCT Section, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Division of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden
23Pediatric Onco-hematology Department, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
24Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom
25Hospital Universitario Virgen de la Arrixaca, University of Murcia, El Palmar, Murcia, Spain
26Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Padova, Padova, AL, Italy
27EBMT Paris Study Unit, Paris, France
28Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany
29EBMT Statistical Unit, Paris, France

Background: Pediatric patients younger than two years of age with acute myeloid leukemia (AML) commonly receive a chemotherapy-based myeloablative conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT). The optimal choice of cytotoxic agents is still controversial.

Methods: A retrospective EBMT-registry based study was conducted to investigate the impact of different chemotherapy-based conditionings on the outcomes in young children. Children younger than two years of age receiving a first HSCT of bone marrow (BM), peripheral blood stem cells (PBSC) or cord blood (CB) from matched siblings (MSD) or unrelated donors (UD) in first complete remission (CR1) between 2000 and 2019 were included. Busulfan/Cyclophosphamide (BuCy) and BuCy/Melphalan (BuCyMel) were the most frequent combinations on which this analysis focused. The primary endpoint was leukemia-free survival (LFS). Multivariate analysis adjusting for differences between the conditioning regimens and risk factors influencing outcome was performed using the Cox’s proportional hazards regression model.

Results: 289 patients (56% male) transplanted at a median age of 1.2 years (IQR 0.9-1.6) after BuCy (164, 57%) or BuCyMel (125, 43%) were included. 184 (64%) patients received BM, 71 (24%) CB and 34 (12%) PBSC from UD (201, 70%) and MSD (88, 30%). In-vivo T-cell-depletion (TCD) was performed in 160 (58%, missing data 14) of the HSCTs with anti-thymocyte-globulin (ATG, 153) or alemtuzumab (7). Ex-vivo TCD was performed in 13 (5%, missing data 3) of the HSCTs. Graft-versus-host-disease (GvHD)-prophylaxis was Cyclosporin-A-based in 90% of the HSCTs. Median follow-up (FU) was 4.9 years (95% CI 3.9-5.5).

After a median FU of 4 years, 4-y-LFS after BuCyMel (74.3%, 95% CI 65.1-81.4) was significantly better compared to BuCy (59.7%, 95% CI 51.2-67.2), hazard ratio (HR) 0.56 (95% CI 0.35-0.90, P=0.02). Overall survival (4-y-OS) after BuCyMel (77.2%, 95% CI 68.1-84.0) was significantly better compared to BuCy (66.6%, 95% CI 58.0-73.8), HR=0.58 (95% CI 0.35-0.97, P=0.04).

No significant differences were found in the probability of relapse (4-y-RI (whole cohort) 26.2% (95% CI 21.0-31.7), HR of BuCyMel 0.59 (95% CI 0.34-1.02), P=0.06), non-relapse mortality (4-y-NRM (whole cohort) 7.8% (95% CI 5.0-11.4), HR of BuCyMel 0.49 (95% CI 0.19-1.24), P=0.13) and incidence of acute grade II-IV GvHD at day 100 (day-100-aGvHD II-IV (whole cohort) 36.8% (95% CI 31.2-42.5), HR of BuCyMel 0.59 (95% CI 0.35-1.01), P=0.06). Incidence of chronic GvHD (4-y-cGvHD (whole cohort)) was 9.8% (95%-CI 6.3-14.2). The donor type had no significant influence on the outcome.

Conclusion: Bu-based conditionings of HSCT for infants with AML at high risk of relapse offer a high probability of cure. Conditioning with three alkylators (BuCyMel) resulted in better LFS and OS compared with two alkylators (BuCy) without significantly increasing the risk of both NRM and aGvHD. Future trials will evaluate the impact of the more recently introduced alkylator Treosulfan within the conditioning of HSCT in pediatric AML.

Disclosures: Peters: Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants. Locatelli: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Miltenyi: Speakers Bureau; Medac: Speakers Bureau; Jazz Pharamceutical: Speakers Bureau; Takeda: Speakers Bureau. Moraleda: Pfizer: Other: Educational Grants, Research Funding; Sanofi: Other: Educational Grants, Research Funding; MSD: Other: Educational Grants, Research Funding; ROCHE: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Takeda: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Sandoz: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Educational Grants, Research Funding; NovoNordisk: Other: Educational Grants, Research Funding; Janssen: Other: Educational Grants, Research Funding; Celgene: Other: Educational Grants, Research Funding; Amgen: Other: Educational Grants, Research Funding. Biffi: BlueBirdBio: Consultancy, Other: Advisory Board. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria.

*signifies non-member of ASH