June 2024

Researchers conducted a multi-center, single-arm, Phase II clinical trial (NCT01850108) investigating the efficacy and safety of haploidentical (partially matched related donor) bone marrow transplant (BMT) with non-myeloablative conditioning (non-MAC) in patients with sickle cell disease (SCD). The study aimed to evaluate whether this approach could achieve a 2-year event-free survival (EFS) rate of at least 80%, utilizing a collaborative learning model among multiple international sites. Results support the broader adoption of this protocol, potentially expanding access to curative treatment for SCD patients.

Download a PDF to the study highlights and citation here

Background

Sickle cell disease is a severe genetic disorder characterized by painful vaso-occlusive episodes and chronic organ damage, leading to reduced life expectancy. Allogeneic hematopoietic cell transplant (HCT) remains the only curative treatment, but it faces challenges, including donor availability and the risks associated with MAC regimens. Haploidentical BMT with non-MAC regimens has emerged as a potential option, but previous studies have reported high graft failure rates of up to 40%. This trial sought to improve outcomes using a conditioning regimen that included thiotepa and post-transplant cyclophosphamide (PTCy).

Methods

The study enrolled 70 evaluable patients aged 1-70 years (median age 19.1 years) diagnosed with SCD who lacked an HLA-matched sibling donor but had a suitable related haploidentical donor. Participants were recruited from 8 sites across North America, Europe and Asia. The primary outcome measures were 2-year EFS, 2-year overall survival (OS) and graft failure rates. The median follow-up time was 2.4 years, with results reported for participants with at least 1 year of follow-up.

Results

The study achieved its primary endpoint with a 2-year EFS of 82.6%. However, outcomes varied by age, with pediatric patients showing poorer EFS compared to adults. The 2-year OS was 94.1%, with no significant difference between age groups.

Graft failure was observed in 11.4% of patients, all of whom were under 18 years old. Among those with successful engraftment, 96.6% were off immunosuppression by 1-year post-transplant. The incidence of severe acute graft-versus-host disease (GVHD) was 10.0%, and moderate-severe chronic GVHD was also 10.0%, with children experiencing a higher rate of chronic GVHD than adults. Five participants (7.1%) died due to infectious complications.

Key takeaways

This Phase II trial demonstrated that haploidentical BMT with non-MAC regimens and PTCy can achieve favorable outcomes in SCD patients, particularly in adults, with an EFS of over 80% and OS exceeding 90%. However, the approach may be less effective in pediatric patients, who experienced higher rates of graft failure and chronic GVHD. The study supports the broader adoption of this protocol in middle and high-income countries, potentially expanding access to curative treatment for SCD patients who lack a matched sibling donor.

Figure

This figure shows OS and EFS between the pediatric and adult study cohorts.