Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, Registries
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.