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595 Role of Age and Donor Type in 3646 Severe Aplastic Anemia Patients Undergoing Hematopoietic Stem Cell Transplantation in 2011-2020: A Retrospective EBMT-Saawp Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 723. Allogeneic Transplantation: Long-Term Follow up and Disease Recurrence: Long-term Outcomes Including in Bone Marrow Failure and Rare Diseases
Hematology Disease Topics & Pathways:
Research, Bone Marrow Failure Syndromes, Clinical Research, Aplastic Anemia, Diseases, Real-world evidence, Registries, Survivorship
Sunday, December 8, 2024: 12:00 PM

Antonio M Risitano, MD, PhD1,2, Dirk-Jan Eikema Sr.3*, Joe Tuffnell4*, Brian Piepenbroek5*, Victoria Potter6*, Flore Sicre De Fontbrune7,8*, Malek Benakli, MD9*, Krzysztof Kalwak Sr.10*, Elena Skorobogatova Sr.11*, Alexey Maschan, MD, DSc12*, Alexander Kulagin, MD, PhD13*, Jean-Hugues Dalle, MD, PHD14, Ashrafsadat Mousavi15*, Ali Al-Ahmari, MD16*, Caroline Besley, MD17*, Mohsen Al Zahrani18*, Henrik Sengeloev19*, Constantijn J.M. Halkes, MD20*, Rawad Suleiman Rihani, MBBS, MD21*, Mahmoud Aljurf22*, Estelle Verburgh, MBChB, M Med Int, FCPSA, PhD23, Jennifer Clay Sr., MD, PhD24*, Carlos Pinho Vaz25*, Khaled Halahleh Sr., MD26*, Sarah Lawson27*, Nour Ben Abdeljelil, MD28*, Marica Laurino, MD29*, Jakob Passweg Sr.30, Emma Nicholson, MD31*, Ben Carpenter, MD32*, Franco Locatelli, MD33, Matthias Stelljes, MD34*, Matjaz Sever, MD, PhD35, Camilla Frieri36,37*, Austin G. Kulasekararaj, MD, MBBS, FRCPath, MRCP38 and Regis Peffault De Latour39,40*

1Severe Aplastic Anemia Working Party, European Group for Blood and Marrow Transplantation (EBMT), Leiden, Netherlands
2Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy
3EBMT Statistical Unit, Leiden, Netherlands
4EBMT Leiden Study Unit, Leiden, Netherlands
5EBMTClinical Study Unit, Leiden, Netherlands
6Dept. of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom
7Hematology and Transplant Unit, Saint Louis Hospital, APHP, Paris, France
8French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint Louis Hospital, Paris, France
9Pierre and Marie Curie Center, Algiers, Algeria
10Fundacja "Na Ratunek Dzieciom z Choroba Nowotworowa", Wroclaw, Dolnoslaskie, Poland
11The Russian Federationn Children's Research Hospital, MOSCOW, Russian Federation
12Dmitriy Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
13RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russian Federation
14Department of Pediatric Hematology and Immunology, University Hospital Robert Debré, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France
15Shariati Hospital, Teheran, Iran (Islamic Republic of)
16King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
17Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom
18King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
19Rigshospitalet, Copenhagen, Denmark
20Hematology, Leiden University Medical Center, Leiden, Netherlands
21King Hussein Cancer Centre Pediatric BMT Program, Amman, Jordan
22King Faisal Specialist Hospital & Research Centre, Oncology (Section of Adult Haematolgy/BMT) – Riyadh, Saudi Arabia, Riyadh, Saudi Arabia
23University of Cape Town, Cape Town, South Africa
24Yorkshire Blood & Marrow Transplant Program, Leeds, United Kingdom
25Inst. Português de Oncologia do Porto, Porto, Portugal
26King Hussein Cancer Centre Adult BMT Program, AMMAN, Jordan
27Birmingham Children`s Hospital, Birmingham, United Kingdom
28Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia
29UO Ematologia e terapie cellulari, IRCCS Ospedale Policlinico San martino, Genova, Italy
30University Hospital Basel, Basel, Switzerland
31Royal Marsden NHS Foundation Trust, London, United Kingdom
32University College London Hospitals NHS Foundation Trust, London, United Kingdom
33Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Catholic University of the Sacred Heart, Rome, Italy
34Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany
35UNIVERSITY CLINICAL CENTRE, LJUBLJANA, Slovenia
36Hematology and Transplant Unit, A.O.R.N. S. Giuseppe Moscati, Avellino, Italy
37European Bone Marrow Transplantation society, Severe Aplastic Anemia Working Party, Leiden, Netherlands
38King’s College Hospital-NHS Foundation Trust, NIHR/Wellcome King’s Clinical Research Facility, and King’s College London, London, United Kingdom
39BMT unit, Hôpital Saint-Louis,, Paris, France
40French Référence Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment option for patients with acquired aplastic anemia (AA). However, in patients above 40 years of age the overall survival remains below 60% at 3 years (Giammarco et al, Blood 2018). We decided to investigate the impact of age and donor type on the outcome of patients with AA given HSCT in the decade 2011-2020.

Methods

All consecutive HSCT for acquired AA performed at EBMT centers between 2011 and 2020 were evaluated (inherited AA and second HSCT were excluded). Data were retrieved from the EBMT registry Promise, which includes detailed information about the underlying disease, HSCT procedure, and treatment outcomes, including engraftment, graft failure, acute and chronic graft-versus-host disease (GvHD), overall survival (OS), as well as GvHD/relapse-free survival (GRFS). Role of year of HSCT, age, donor type, interval from diagnosis, previous immunosuppressive treatment (IST), HSCT-comorbidity index and donor age on patient outcomes were investigated.

Results

A total of 3464 AA patients underwent HSCT in the decade 2011-2020 in 365 EBMT transplant centers, with a median follow up of 3.2 years (95% CI 3-3.3). Indications for BMT were moderate AA in 10.7%, severe AA in 61.8%, and very severe AA in 27.5% of patients. Median age at HSCT was 20.9 years (interquartile range 12.2-35.5), with proportion of patients aging <18, 18-40 and >40 years of 40.9%, 39.1% and 19.9%, respectively. Patients were transplanted either from an HLA-matched sibling (MSD; 51.2%), matched unrelated (MUD; 30.8%), mismatched-unrelated (MMUD; 9.8%) or mismatched haplo-identical (Haplo; 8.2%) donor. Three- and five- OS were 81% and 80%; globally, with a better 3-year OS in HSCT performed in the second quinquennium (83% vs 79%, p<0.001).

In MVA, period of HSCT (2016-2020 vs 2011-2015, HR 0.63; p<0.001), age (reference <18; HR 1.54 for 18-40, 2.41 for 41-50, 2.80 for 51-60 and 3.93 for >60; each p<0.001), donor type (reference MSD; HR 1.26 for MUD [p=0.04], 2.10 for MMUD [p<0.001] and 4.20 for Haplo [p<0.001]), interval from diagnosis (cut-off at 6 months, HR 1.24; p=0.03), HSCT-comorbidity index (HR 1.39 and 1.56 for intermediate and high risk; p=0.01 and <0.001) and donor age (p<0.001) all impacted OS. For patients with available information (n=930) about previous IST, 3-year OS was affected by year of HSCT (2016-2020, HR 0.65, p=0.01), age (HR 2.37 for 51-60 [p=0.001] and 2.84 for >60 [p<0.001]), and donor type (HR were 2.38 for MMUD and 2.63 for Haplo, both p<0.001), but not interval from diagnosis or previous IST.

In MSD recipients, estimates of 3-year OS were 93%, 87%, 69%, 71% and 59% in patients <18, 18-40, 41-50, 51-60 and >60 (p<0.001). The same estimates were 89%, 81%, 76%, 64% and 65% in MUD recipients (p<0.001), 78%, 66%, 76%, 48% and 61% in MMUD recipients (p=0.003), and 67%, 62%, 50%, 52% and 15% in Haplo recipients (p<0.001). Recipient age did not impact on neutrophil engraftment, graft failure (primary or secondary) or acute GvHD, while it significantly affected platelet engraftment (p=0.007), chronic GvHD (p<0.001) and GRFS; instead, donor type affected all neutrophil and platelet engraftment (p=0.031 and p<0.001), primary and secondary graft failure (p=0.003 and p<0.001), acute and chronic GvHD (p<0.001 for both) and GRFS. Estimates of 3-year GRFS according to age (<18, 18-40, 41-50, 51-60 and >60) were 73%, 68%, 61%, 54% and 53%; 3-year estimates of GRFS according to donor type (MSD, MUD, MMUD and Haplo) were 73%, 65%, 58% and 54%, respectively (p<0.001). Investigating cause of death at 3 years, recipient age affected infectious mortality (6%, 8%, 14%, 22% and 22 in <18, 18-40, 41-50, 51-60, >60; p<0.001), but not mortality from GvHD or other specific causes.

Conclusion

We showed that HSCT outcome improved in recent years, and that age and donor type continue to be the most important factors affecting OS after HSCT for AA, mostly due to infectious mortality. However, the age threshold driving HSCT mortality largely depend on donor type. Indeed, survival rates meaningfully decline in recipient >60 for MSD, >50 for MUD and MMUD, and >40 for Haplo. Nevertheless, prospective studies are needed to guide treatment decisions.

Disclosures: Risitano: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Apellis: Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; Sobi: Consultancy, Speakers Bureau. Sicre De Fontbrune: pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Jazz pharmaceuticals: Consultancy, Honoraria. Dalle: Pfizer: Consultancy, Honoraria; Vertex: Consultancy, Honoraria; Symbiopharm: Consultancy, Honoraria; Teva: Current equity holder in private company; Novartis: Consultancy, Honoraria; Pierre Fabre Médicaments: Consultancy, Honoraria, Other: travels; Orchard: Consultancy, Honoraria. Verburgh: CANSA: Research Funding; NIH: Research Funding; Roche: Honoraria; Takeda: Honoraria; MSD: Research Funding; South African Stem Cell Transplantation Society: Membership on an entity's Board of Directors or advisory committees. Nicholson: BMS/Celgene: Honoraria; Novartis: Honoraria; Kite/Gilead: Honoraria, Research Funding; Autolus: Membership on an entity's Board of Directors or advisory committees. Carpenter: Vertex Pharmaceuticals Incorporated: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird Biotech: Honoraria. Stelljes: Takeda: Consultancy; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Medac: Honoraria, Other: Travel- & congress-support; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Incyte: Consultancy, Honoraria; BMS: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel- & congress-support, Research Funding; Celgene: Honoraria; Abbvie: Honoraria. Kulasekararaj: Silence Therapeutics: Honoraria; Janssen: Consultancy; BioCryst: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Speakers Bureau; Samsung: Consultancy, Honoraria, Speakers Bureau; Akari: Consultancy, Honoraria, Speakers Bureau; Achillion: Consultancy, Honoraria, Speakers Bureau; Agios: Honoraria; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ra Pharma: Consultancy, Honoraria, Speakers Bureau; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau. Peffault De Latour: pfizer: Consultancy, Honoraria, Research Funding; soby: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Honoraria, Research Funding; alexion: Consultancy, Honoraria, Research Funding.

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