Hematopoietic stem cell transplantation for B-thalassemia major with alemtuzumab

Abstract

While matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for transfusion-dependent beta-thalassemia (TDT), the use of alternative sources has increased, resulting in the exploration of novel transplant-conditioning regimens to reduce the contribution of graft-versus-host disease (GVHD) and graft failure (GF) to transplant-related morbidity and mortality. Alemtuzumab is a CD52 monoclonal antibody that has been successfully incorporated into myeloablative conditioning regimens for other hematologic conditions, yet there have been limited studies regarding the use of alemtuzumab in HSCT for TDT. The purpose of this study was to evaluate engraftment, incidence of GVHD, and transplant related morbidity and mortality in patients with TDT who received alemtuzumab in addition to standard busulfan-based conditioning. The primary endpoint was severe GVHD-free, event-free survival (GEFS). Our cohort included 24 patients with a median age of 6.8 years (range 1.5-14.9). Eleven patients received a 10/10 MRD HSCT, eleven 10/10 unrelated donor (UD), and two mismatched UD. All patients achieved primary engraftment. For all patients, 5-year GEFS was 77.4% and 5-year overall survival (OS) was 91%. The 5-year cumulative incidence of GF (attributed to poor graft function) without loss of donor chimerism was 13.8% (95% CI: 4.5, 35.3). We report low rates of significant acute GVHD grade II–IV (12.5%) and chronic GVHD (4.4%). Younger age and MRD were associated with significantly improved GEFS, OS and EFS. Our results show that the use of alemtuzumab promotes stable engraftment, may reduce rates of severe GVHD, and results in acceptable GEFS, OS, and EFS.

Keywords:

• Alemtuzumab
• hematopoietic stem cell transplantation
• transfusion-dependent beta-thalassemia

Acknowledgments

The authors would like to express sincere appreciation to the members of the Center for Cell and Gene Therapy for their valuable contributions to this manuscript. We would like to especially acknowledge Dr. Helen Heslop for her support. Their expertise and insights have been instrumental in providing a comprehensive overview of the outcomes of patients who underwent a hematopoietic stem cell transplantation for B-Thalassemia Major with alemtuzumab.

Contributions

LMS and TDJ drafted the paper. LMS, AG and SB were responsible for extracting data. LMS and BDF analyzed the data. BDF contributed with the statistical analysis of survival outcomes and creation of Figure 2. GS, EED, JC, DS, BS, BO, KY, KL, CM, RAK and TDJ provided feedback on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Disclaimer

We declare that there are no disclaimers to be made in this submission.

Data availability statement

Datasets may be available upon request via corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.