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Updated: Jul 16, 2025
A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Excellent outcome of stem cell transplantation for sickle cell disease
Tanja Vallée1, Irene Schmid1, Lisa Gloning1
1Department of Pediatrics, Dr. Von Hauner Children's Hospital, University Hospital, LMU Munich, Lindwurmstr. 4, 80337, Munich, Germany.
Insights
Reduced toxicity conditioning for sickle cell disease (SCD) patients using matched family donors (MFD), matched unrelated donors (MUD), or matched-mis-matched family donors (MMFD) resulted in excellent survival and low GVHD. Treosulfan conditioning was associated with higher graft failure rates compared to busulfan.
Area of Science:
- Hematology
- Transplantation Immunology
- Pediatric Hematology
Background:
- Sickle cell disease (SCD) patients often lack matched family donors (MFD) or matched unrelated donors (MUD), making haploidentical donors (MMFD) a viable option.
- Hematopoietic stem cell transplantation (HSCT) is a potential cure for SCD, but donor availability remains a challenge.
Purpose of the Study:
- To evaluate the efficacy and safety of a reduced toxicity conditioning protocol for HSCT in pediatric and young adult SCD patients across different donor types (MFD, MMFD, MUD).
- To compare outcomes, including survival, graft failure, GVHD, and viral reactivation, based on donor type and conditioning regimen.
Main Methods:
- A cohort of 31 pediatric and young adult SCD patients underwent HSCT with MFD (n=15), MMFD (n=10), or MUD (n=6).
- Conditioning involved alemtuzumab/ATG, thiotepa, fludarabine, and either treosulfan or targeted busulfan, with post-transplant cyclophosphamide for MMFD recipients.
- Follow-up was conducted for a median of 26 months.
Main Results:
- All patients were alive and off immunosuppression at follow-up.
- Two MMFD patients (both with treosulfan conditioning) experienced secondary graft failure.
- No acute GVHD grade III or higher or moderate/severe chronic GVHD was observed.
- Disease-free, severe GVHD-free survival was 100% (MFD), 100% (MUD), and 80% (MMFD).
- Virus reactivation was higher in MMFD (100%) and MUD (83%) groups compared to MFD (40%).
- Graft failure occurred in 2/6 (33%) patients conditioned with treosulfan versus 0/25 (0%) with busulfan (p=0.032).
- 90% of patients achieved donor chimerism >=80%.
Conclusions:
- Reduced toxicity myeloablative conditioning is effective for HSCT in pediatric and young adult SCD patients, achieving excellent survival and low GVHD across all donor types.
- Targeted busulfan conditioning appears superior to treosulfan, showing a significantly lower rate of graft failure.
- Haploidentical HSCT with this reduced toxicity protocol is a promising option for SCD patients lacking MFD or MUD.
Abstract:
Many sickle cell disease (SCD) patients lack matched family donors (MFD) or matched unrelated donors (MUD), implying haploidentical donors (MMFD) as a logical donor choice. We used a reduced toxicity protocol for all donor types. We included 31 patients (2-22 years) with MFD (n = 15), MMFD (10), or MUD (6) HSCT and conditioning with alemtuzumab/ATG, thiotepa, fludarabine and treosulfan, and post-transplant cyclophosphamide for MMFD. After the initial six patients, treosulfan was replaced by targeted busulfan (AUC 65-75 ng*h/ml). After a median follow-up of 26 months (6-123), all patients are alive and off immunosuppression. Two MMFD patients experienced secondary graft failure with recurrence of SCD, both after treosulfan conditioning. Neither acute GVHD ≥ °III nor moderate/severe chronic GVHD was observed. The disease-free, severe GVHD-free survival was 100%, 100%, and 80% in the MFD, MUD, and MMFD groups, respectively (p = 0.106). There was a higher rate of virus reactivation in MMFD (100%) and MUD (83%) compared to MFD (40%; p = 0.005), but not of viral disease (20% vs 33% vs 13%; p = 0.576). Six patients had treosulfan-based conditioning, two of whom experienced graft failure (33%), compared to 0/25 (0%) after busulfan-based conditioning (p = 0.032). Donor chimerism was ≥ 80% in 28/31 patients (90%) at last follow-up. Reduced toxicity myeloablative conditioning resulted in excellent overall survival, negligible GVHD, and low toxicity among all donor groups in pediatric and young adult patients with SCD.
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