Busulfan–fludarabine- or treosulfan–fludarabine-based myeloablative conditioning for children with thalassemia major

Abstract

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfanfludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.

Benefits and Risks in Polypathology and Polypharmacotherapy Challenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease

“…Graft versus host disease was the major complication with grade II-IV acute and chronic incidence to range to about 24% and 13% respectively [186]. Similar results were obtained in other short and long term monitoring studies of HSCT TM patients [7,[182][183][184]187]. Overall, it appears that in general young and non-iron loaded patients with nonunderlying co-morbidities have the highest prospects of OS and TFS from the HSCT TM patients.…”

“…This therapeutic method is subject to suitable donor availability and offers the complete treatment of TM especially for young TM children. The ther-apy has been developed for TM following many years of monitoring and investigations mainly on improving the transplant procedure and also treating the short and long term toxic side effects of transplantation including graft rejection, chimerism, graft versus host disease (GvHD), infections, myeloablative conditioning regimens, the use of matched or mismatched donors and in patients of different ages, iron loading and with different underlying comorbidities [7,8,[182][183][184][185]. In this context, many different factors appear to influence the overall survival (OS) and thalassaemia -free survival (TFS) of HSCT TM patients in different countries and transplantation centers.…”

Treosulfan Versus Busulfan-based Conditioning in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-analysis

“…In the end, 6 studies were included in this review. [9][10][11][14][15][16] The baseline details of the 6 studies are shown in Table 1. One study was from India, whereas all others were from Europe.…”

“…Six of them were on adult patients, whereas 2 did not report relevant outcomes and hence were excluded. In the end, 6 studies were included in this review 9–11,14–16 …”

“…Olivas-Mazon et al 16 reported data on malignant and nonmalignant cases separately and hence are tabulated in different rows in Table 1. Only one study 15 was of large sample size, whereas others included 11 to 61 patients per group. Most studies used cyclosporine for GVHD prophylaxis.…”