-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.

5079 Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) Outcomes in Leukocyte Adhesion Deficiency Type -I

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, Registries
Monday, December 9, 2024, 6:00 PM-8:00 PM

Claire Booth, MBBS, PhD1,2*, Patrick Gilbert3*, Luuk Gras4*, Hawazen Alsaedi5*, Amir Ali Hamidieh6*, Mor Seny Gueye7*, Mary Slatter, MD8*, Ashrafsadat Mousavi9*, Amos Toren10*, Musa Karakukcu, MD11*, Abdelghani Tbakhi12*, Polina Stepensky13*, Gulyuz Ozturk14*, Peter Bader15, Henrik Sengeloev16*, Tayfun Güngör17*, R.F. Wynn18*, Franco Locatelli, MD19, Maria Chitty-Lopez, MD20*, Joana E Matos20*, Stuart Turner20*, Gayatri R Rao, MD, JD20*, Jonathan D Schwartz, MD20, Michael H Albert21* and Bénédicte Neven22*

1University College London Great Ormond Street Institute of Child Health, London, United Kingdom
2Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital NHS Trust, London, United Kingdom
3EBMT Leiden Study Unit, Leiden, Netherlands
4EBMT, Leiden, Netherlands
5King Faisal Specialist Hospital and Research Centre, Riyadh, SAU
6Pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran (Islamic Republic of)
7Hospital Necker-Enfants Malades, Paris, France
8Paediatric Stem Cell Transplant Unit, Great North Children’s Hospital, Newcastle Upon Tyne, United Kingdom
9Shariati Hospital, Teheran, Iran (Islamic Republic of)
10Sheba Medical Center, Tel-Hashomer, Israel
11Pediatri Hematoloji Onkoloji Başkanı, Erciyes Üniversitesi, Kayseri, Turkey
12King Hussein Cancer Foundation and Center, Amman, Jordan
13Hadassah University Hospital, Jerusalem, Israel
14Acibadem Saglik Hizmetleri ve Ticaret Anonim Sirketi, Istanbul, TUR
15Universitätsklinikum Frankfurt Goethe-Universität, Frankfurt, Germany
16Rigshospitalet, Copenhagen, Denmark
17Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, University Children's Hospital Zurich-Eleonore Foundation & Children's Research Center, Zürich, Switzerland
18Royal Manchester Children's Hospital, Manchester, United Kingdom
19IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy
20Rocket Pharmaceuticals, Inc., Cranbury, NJ
21Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
22Unité d'Immuno-Hématologie et Rhumatologie Pédiatrique, Assistance Publique-Hôpitaux de Paris, Paris, France

Background: Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive inborn error of immunity caused by loss of function mutations in ITGB2, which encodes for the β2 common integrin subunit CD18, impairing leukocyte adhesion to inflamed endothelium and migration to sites of infection or injury. Allo-HSCT represents the only therapeutic option to enable survival beyond early childhood but is limited by donor availability, risk of infections, graft-versus-host disease (GvHD) and graft failure (GF).

Objective: To characterize outcomes of patients with LAD-I who underwent allo-HSCT over a very recent 10-year period in a large European cohort.

Methods: The European Society for Blood and Marrow Transplantation (EBMT) registry allo1 database was queried for patients with LAD-I who received an allo-HSCT using a single stem cell source between 2012 and 2021 and were under 12 years old at the time of transplant.

Patient, donor, and transplant characteristics were summarized using descriptive statistics. Ninety-five percent confidence intervals (CI) were calculated for overall survival (OS) and event-free survival (EFS). EFS was defined as survival without GF and/or grade II-IV acute GvHD (aGvHD). Percentages for categories with missing patient data were calculated based on the number of patients with available data.

Results: Among 56 patients with LAD-I who met the inclusion criteria, the median age at diagnosis was 2.0 months (IQR: 0.4-2.2) and median time from diagnosis to transplant was 6.8 months (IQR: 2.9-15.5). All patients received a conditioning regimen, with 80.4% receiving myeloablative conditioning. Most patients (80.4%) received serotherapy (mainly with ATG and alemtuzumab); and 98.2% received GvHD immunosuppressive prophylaxis. Among patients with available information, recipient/donor cytomegalovirus (CMV) status mismatch (−/+ and +/-) was present in 19.2% and 5.8%, respectively. Human Leukocyte Antigens (HLA) matched sibling donor (MSD) recipients comprised 39.3% of the cohort, matched unrelated family donors, 30.4%, matched unrelated donors, 12.5%, mismatched donors, 16.1% and unrelated donors, 1.8%. Transplant-related complications, including veno-occlusive disease, transplant-associated microangiopathy and renal insufficiency among others occurred in 31% of patients. Post-transplant infection-related hospitalizations occurred in 45.5% of patients. GF occurred in 16.4% of patients, while 27.3% developed aGvHD (Grade II-IV) and 7.7% developed chronic GvHD. Overall, the mortality rate was 14.3%.

OS at 1 and 3 years in the total patient population was 85% (95% CI: 75–95%). Recipient/donor CMV status was significantly associated with OS (p=0.003) with mismatched -/+ and +/- recipient 1 year and 3 year survival of 57% (range: 25-89%) and 67% (range: 13-100%) respectively; 1-3 year OS was 86% (range: 60-100%) and 100% for -/- and +/+ patients (no deaths occurred between year 1 and 3). The 1-year EFS in the total patient population was 58% (range: 45–71%). EFS at 1 year was highest in MSD recipients (86% [range: 71-100%]), whereas it was lowest among patients with HLA mismatched donors (33% [range: 3-64%]). EFS at 3 years was the same as EFS at 1 year in the total patient population and across HLA matched subgroups, as no additional events were recorded after the first year post-transplant in any group.

Conclusions: Allo-HSCT is the current standard-of-care for definitive treatment for LAD-I. However, despite a better OS in patients with LAD-I undergoing allo-HSCT, GvHD, GF, and other transplant-related complications remain significant sources of transplant-related morbidity, as shown in this recent cohort. These findings highlight the need for more effective and safer treatment approaches, including possibly lentiviral-based gene therapy.

Disclosures: Booth: Ensoma: Consultancy; Rocket Pharmaceuticals Inc.: Consultancy; Chiesi Farmaceutici S.p.A.: Honoraria. Toren: Minovia Therapeutics: Research Funding. Bader: Amgen, Novartis, Vertex: Speakers Bureau; Medac, Novartis, Vertex: Other: Travel grants . Güngör: Neovii: Other: Travel Grand; Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Forge: Membership on an entity's Board of Directors or advisory committees. Chitty-Lopez: Rocket Pharmaceuticals, Inc.: Current Employment. Matos: Rocket Pharmaceuticals, Inc.: Current Employment. Turner: Rocket Pharmaceuticals, Inc.: Current Employment. Rao: Rocket Pharmaceuticals, Inc.: Current Employment. Schwartz: Rocket Pharmaceuticals, Inc.: Current Employment. Albert: Medac: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH