Efficacy and safety of ruxolitinib in ineffective erythropoiesis suppression as a pretransplantation treatment for pediatric patients with beta-thalassemia major.
Beta-thalassemia major
hematopoietic stem cell transplantation
ineffective erythropoiesis
pediatric patients
ruxolitinib
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
22
08
2021
received:
23
05
2021
accepted:
23
08
2021
pubmed:
15
9
2021
medline:
19
3
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Ineffective erythropoiesis (IE) is the most prominent feature of transfusion-dependent beta-thalassemia (TDT), which leads to extramedullary hemopoiesis. The rejection rate in allogeneic hematopoietic stem cell transplantation (HSCT) is high in heavily transfused patients with TDT accompanied by prominent IE. Therefore, a pretransplantation treatment bridging to HSCT is often used to reduce allosensitization and IE. Ruxolitinib is a JAK-1/JAK-2 inhibitor and has showed its efficacy in suppressing IE and the immune system. A previously published study on RUX in adult patients with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated. Ten patients (5-14 years old) with TDT and an enlarged spleen were enrolled. The dose of ruxolitinib was adjusted for age: for patients <11 years: 40-100 mg/m After the first 3 months of ruxolitinib therapy, spleen volume decreased in 9 of 10 cases by 9.1%-67.5% (M = 35.4%) compared with the initial size (P = 0.003). The adverse events of ruxolitinib (infectious complications, moderate thrombocytopenia, and headache) were successfully managed by reducing the dose. The outcomes of HSCT were favorable in seven of eight cases. Ruxolitinib is promising as a short-term pre-HSCT treatment for pediatric patients with TDT and pronounced IE.
Sections du résumé
BACKGROUND
Ineffective erythropoiesis (IE) is the most prominent feature of transfusion-dependent beta-thalassemia (TDT), which leads to extramedullary hemopoiesis. The rejection rate in allogeneic hematopoietic stem cell transplantation (HSCT) is high in heavily transfused patients with TDT accompanied by prominent IE. Therefore, a pretransplantation treatment bridging to HSCT is often used to reduce allosensitization and IE. Ruxolitinib is a JAK-1/JAK-2 inhibitor and has showed its efficacy in suppressing IE and the immune system. A previously published study on RUX in adult patients with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated.
PROCEDURE
Ten patients (5-14 years old) with TDT and an enlarged spleen were enrolled. The dose of ruxolitinib was adjusted for age: for patients <11 years: 40-100 mg/m
RESULTS
After the first 3 months of ruxolitinib therapy, spleen volume decreased in 9 of 10 cases by 9.1%-67.5% (M = 35.4%) compared with the initial size (P = 0.003). The adverse events of ruxolitinib (infectious complications, moderate thrombocytopenia, and headache) were successfully managed by reducing the dose. The outcomes of HSCT were favorable in seven of eight cases.
CONCLUSION
Ruxolitinib is promising as a short-term pre-HSCT treatment for pediatric patients with TDT and pronounced IE.
Substances chimiques
Nitriles
0
Pyrazoles
0
Pyrimidines
0
ruxolitinib
82S8X8XX8H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29338Informations de copyright
© 2021 Wiley Periodicals LLC.
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