-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

508 Younger Haploidentical Versus Older Matched Sibling Donors in Acute Lymphoblastic Leukemia: A Study from the ALWP of EBMT

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Optimizing Conditioning and Donor Selection in Allogeneic Stem Cell Transplantation
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Clinical Research, Diseases, Registries, Lymphoid Malignancies
Sunday, December 8, 2024: 10:15 AM

Eolia Brissot1,2, Myriam Labopin3*, Didier Blaise, MD, PhD4, Cristina Castilla-Llorente, MD5*, Annoek E. C. Broers, MD6*, Nicolaus Kröger, MD Prof7*, Jakob R. Passweg8, Andrew Bruce McDonald, MBBS9*, Lucía López-Corral10*, Zinaida Peric11*, Sebastian Giebel, MD, PhD12*, Arnon Nagler, MD13, Mohamad Mohty, MD, PhD14,15, Fabio Ciceri, MD16*, Francesca Kinsella17* and Ludovic Gabellier, MD, PhD18*

1Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France, Paris, France
2Service d’hématologie et des maladies du sang, Hôpital Saint-Antoine, NOGENT SUR MARNE, France
3EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
4Program of Transplant and cellular immunotherapy, Department of Hematology, Institut Paoli Calmettes, Marseille, France
5Gustave Roussy Cancer Campus, Villejuif, France
6Erasmus MC Cancer Institute, Rotterdam, Netherlands
7Department of Stem Cell Transplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
8University Hospital Basel, Basel, Switzerland
9Alberts Cellular Therapy, Netcare Pretoria East Hospital, Pretoria, South Africa
10University Hospital of Salamanca, Salamanca, Spain
11Department of Haematology, University Hospital Centre Rijeka, Rijeka, Croatia
12Department of Hematology and Bone Marrow Transplantation, Maria Sklodowska-Curie Institute of Oncology, Gliwice, Poland
13Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Aviv, Israel
14Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France
15Hematology Dpt, Hopital Saint-Antoine, University UPMC, INSERM, Paris, France
16Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
17Birmingham Centre for Cellular Therapy and Transplant (BCCTT), Birmingham, United Kingdom
18Hematology Departement, CHU Montpellier University Hospital, UMR-CNRS 5535, Montpellier, France

Donor selection is fundamental to the success of allogeneic hematopoietic stem cell transplantation (HSCT). Although matched sibling donors (MSD) are the reference donors, the young age of the donor is a well-established prognostic factor in many studies. With the increasing prevalence and improved management of haploidentical transplantation in acute lymphoblastic leukemia (ALL), it is unknown whether outcomes differ after HSCT with older MSD (oMSD) compared to younger haploidentical donors (yhaploD).

Therefore, we performed a retrospective analysis comparing the outcomes of ALL patients, aged 45 years and older, in first complete remission (CR1) who underwent HSCT with younger (<40 years) haploD or older (>50 years) MSD between 2012 and 2022. The major endpoints were to assess overall survival, leukemia-free survival, relapse incidence, non relapse mortality, and graft-versus-host disease-free, relapse-free survival (GRFS).

A total of 756 patients were included with a median age of 56.8 years (interquartile range [IQR], 52.1- 61.1). Follow up was longer in the oMSD group compared to the yHaploD group (3.5 years vs 2.1 years, p<0.001). hematopoietic cell transplantation-specific comorbidity Index score, Karnofsky score, gender patient and MRD status at transplantation were similar between the 2 groups. The median age of the donor was 56.3 years (IQR, 52.9-60.9) in the oMSD group versus 29 years (IQR, 22.8-34.6] in the yHaploD group. There was no difference in the intensity of the conditioning regimen between the 2 groups (p=0.4). In univariate analysis, neutrophil engraftment at 30 days was significantly higher in the oMSD group: 98% [95% CI, 96.5-98.9] versus 92% [95%, CI 86.6-95.3] for yHaplo (p<0.001). With a median follow-up of 2 years, NRM was significantly higher and relapse incidence significantly lower in the yHaplo group versus the oMSD group. Survival outcomes at 2 years were distributed as follows for oMSD and yHaplo groups, respectively: overall survival 66.2% (95% CI, 61.8-70.2) versus 65.3% (95% CI, 61.8-70.2), p=0.88; LFS 57.6% (95% CI, 53.2-61.8) versus 62.1% (95% CI, 53.2-69.7), p=0.25; relapse incidence 24.9% (95% CI, 21.2-28.7) versus 11.7% (95% CI, 7-17.8), p=0.001; non-relapse mortality 17.5% (14.3-20.9) versus 26.2% (95% CI 14.3-20.9), p=0.022; GRFS 42.6% (95% CI 38.2-46.9) versus 47.2% ( 95% CI, 38.6-55.4)180-day grade II-IV acute GVHD 24.6% (95% CI, 21.1-28.2) versus 32.1% (95% CI, 24.9-39.4), p=0.06; grade III-IV acute GVHD 8.6% (95% CI, 6.5-11.2) versus 13.2% (95% CI, 8.5-19), p=0.08; chronic GVHD of all grades 43.5% (95% CI, 39-48) versus 39.2% (95% CI, 30.7-47.7), p=0.2; extensive chronic GVHD 22.5% (95% CI, 18.8-26.4) versus 18.2% (95% CI, 11.9-25.6), p=0.15. In multivariate analysis, yHaploD was the only factor associated with lower RI (HR=0.49, 95 %CI, 0.9-2.28, p=0.008). All other outcomes including NRM, LFS, OS, and GRFS did not differ between donor types. Patient age (per 10 years) had a negative impact on LFS (HR=1.25, 95% CI, 1-1.55; p=0.047) and also on OS (HR=1.33, 95% CI, 1.06-1.69, p=0.015). In addition, the use of TBI and a female donor with a male recipient were associated with higher risk of extensive chronic GVHD (HR=1.61, 95% CI, 1.04-2.48, p=0.03 and HR=1.52, 95% CI, 1-2.31, p=0.049; respectively).

In our study, yHaploD seems to be a valid option compared to oMSD for patients undergoing HSCT for ALL in CR1. Indeed, yHaploD significantly reduces the risk of relapse and achieves similar survival outcomes compared to oMSD.

Disclosures: Kröger: Novartis, BMS, Neovii, Kite/Gilead, Sanofi, Takada: Membership on an entity's Board of Directors or advisory committees; Novartis, Neovii, Kite/Gilead, Therakos, Alexion, Sanofi, Takeda: Other: Speaker honoraria; Novartis, DKMS: Research Funding; Provirex: Consultancy. Giebel: Celgene/BMS, Janssen, Pfizer: Speakers Bureau; Miltenyi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kiadis Pharma, The Netherlands: Research Funding; Gilead/Kite: Research Funding, Speakers Bureau; Immunicum/Mendes: Membership on an entity's Board of Directors or advisory committees; Equity Ownership (Private company): Research Funding. Mohty: Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria; GSK: Honoraria; Novartis: Honoraria; Stemline Menarini: Honoraria; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Adaptive: Honoraria; MaaT Pharma: Current equity holder in publicly-traded company. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH