Outcomes of Gene Therapy and Allogeneic Hematopoietic Cell Transplantation for Sickle Cell Disease: A Single-Center Retrospective Analysis

Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for sickle cell disease (SCD) but is limited due donor availability, risk of graft-versus-host disease (GVHD), and a requirement for immunosuppressive therapies (IST). Gene therapy (GT) with autologous transplantation is a novel cellular therapy option that can significantly reduce SCD complications, although long-term data are limited. There are no current prospective studies comparing real-world outcomes across modalities. We retrospectivity reviewed treatment characteristics and clinical outcomes for all patients (pts) with SCD undergoing GT or alloHCT at the University of Alabama in Birmingham between 2019-2025. The goal of the study is to understand differences in the treatment burden and time to recovery between GT or alloHCT. 14 pts with sickle cell anemia (SCA) underwent 15 cellular therapies at our center, including 7 GT (lovo-cel via HGB-206/210 trials) and 8 alloHCT (3 haploidentical donors (haplo) and 5 matched-related donor (MRD)). Baseline characteristics are shown in Table 1. GT pts required 2.5 apheresis sessions on average for target cell collection. Average length of stay (LOS) was 35.5 days in alloHCT vs 31 days in GT (p=0.934). Within 1-year of treatment, there were 9 re-admissions in alloHCT vs 3 in GT (p=0.268). 50% pts required hospital re-admission with 85% within 90 days and 1 alloHCT patient remained inpatient for 60 days. GVHD occurred in 4 alloHCT recipients (50% severe chronic GVHD). Median time of IST was 360 days in alloHCT, excluding 1 patient with ongoing IST for chronic GVHD. Graft failure occurred in 2 alloHCT compared to 0 in GT, both in pts who received non-myeloablative conditioning (alemtuzumab/total body irradiation) for MRD alloHCT with 1 patient then proceeding to a second MRD alloHCT. 1 death occurred from sepsis following alloHCT prior to engraftment in the patient undergoing second MRD alloHCT. 1 patient with mixed chimerism developed chronic myeloid leukemia 3.6 years after alloHCT. Other adverse events included grade 3+ infection (n=5; 3 in alloHCT, 2 in GT), viral reactivation (n=2), priapism (n=1), and retinopathy progression (n=1). 79% required IV opioids for mucositis at average 6.75 days post-treatment, similar between groups. All experienced neutropenia with median onset -0.5 days in alloHCT vs +8 days in GT, as expected with differing conditioning regimens. Fever occurred in 93% at median 8 days without group differences. Transfusion independence was achieved at median 14 days in GT and 20 days in alloHCT (p=0.130). Details of outcomes by patient are shown in Figure 1. In this single-center experience, both GT and alloHCT provided durable engraftment and HbS suppression. Long-term follow-up and larger multi-institutional series are needed to clarify durability of GT and to refine risk-benefit comparisons between these therapies.