Thalassemia in Children
Conditions
Keywords
Thalassemia, HSCT, Hetrombopag
Brief summary
The objective of this observational study is to investigate the long-term effects of Hetrombopag in promoting platelet engraftment during haploidentical hematopoietic stem cell transplantation (HSCT) in children with thalassemia, with a specific focus on a 28-day time window post-transplantation. The core question to be addressed is: Is Hetrombopag safe and effective for platelet engraftment in children with thalassemia undergoing haploidentical HSCT within a 28-day post-transplant period? Subjects who received Hetrombopag as part of routine care for haploidentical HSCT in children with thalassemia will be required to complete a 28-day online survey on platelet engraftment outcomes.
Detailed description
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a critical and often the sole curative modality for diverse hematological malignancies and disorders. Post-transplant thrombocytopenia (platelet count \<20×10⁹/L) significantly compromises long-term patient survival, with an incidence of 5-20% in allo-HSCT recipients, thereby escalating treatment morbidity and costs. Current research on platelet engraftment promotion in pediatric thalassemia patients undergoing allo-HSCT is limited. Repeated platelet transfusions are associated with substantial complications, including transfusion reactions, platelet alloimmunization, and transfusion-transmitted viral infections. Eltrombopag, a thrombopoietin receptor agonist (TPO-RA), carries a black-box warning for hepatotoxicity, with a real-world incidence of 11.8%. Transplant recipients frequently experience diarrhea, which impairs the absorption of oral thrombopoietic agents, while daily subcutaneous injections exacerbate pediatric patient discomfort and reduce treatment adherence. In contrast, long-acting TPO-RAs administered once post-transplant have demonstrated favorable tolerability and promising efficacy in thalassemia transplant pediatric populations. To date, clinical data on Hetrombopag use for platelet recovery in haploidentical HSCT for pediatric thalassemia are lacking. Therefore, this observational study aims to evaluate the efficacy and safety of Hetrombopag in facilitating platelet engraftment during haploidentical HSCT in children with thalassemia.
Interventions
DRUGHetrombopag
In allogeneic hematopoietic stem cell transplantation, hetrombopag is initiated at 3 µg/kg subcutaneously on day +6 post-transplant. The dose is increased by 2 µg/kg weekly up to a maximum of 10 µg/kg. Treatment is discontinued when platelet counts rise to 100×10⁹/L. If platelet counts remain ≤20×10⁹/L on day +20, hetrombopag is combined with eltrombopag 25 mg orally once daily. Fresh apheresis platelet suspensions (1 therapeutic dose, containing \>2.5×10¹¹ platelets) are administered when platelet counts are ≤20×10⁹/L or when counts are between 21-50×10⁹/L with active bleeding. If engraftment has not occurred by day +28 post-transplant, re-transplantation is required, and hetrombopag is considered ineffective.
Sponsors
Haikou Affiliated Hospital of Central South University Xiangya School of Medicine
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with severe thalassemia via thalassemia gene testing, transfusion history, and complete blood count (CBC). * Pediatric patients aged 2-17 years. * Consented to haploidentical transplantation and evaluated by the transplant team as having no transplant contraindications.
Exclusion criteria
* Presence of a fully matched donor with refusal of haploidentical transplantation. * Donor or recipient with transaminase levels \>2× the upper limit of normal (ULN). * Positive hepatitis B DNA test result. * Active infection at the time of enrollment. * Donor-specific antibodies (DSA) \>5,000 and unable to decrease below 3,000 after antibody therapy. * Presence of transplant contraindications as assessed by the transplant team.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet recovery time | From enrollment to 28 days after transplantation | The time at nodes such as platelet \>20×10\^9/L, 50×10\^9/L and 100×10\^9/L |
| Platelet transfusion volume | From enrollment to 28 days after transplantation | Required dosage of platelet suspension |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The rate of adverse drug reactions | From enrollment to 28 days after transplantation | The rate of adverse drug reactions occurring during the follow-up period |
| Bleeding incidence rate | From enrollment to 28 days after transplantation | The incidence rate of bleeding during the follow-up period |
| Thrombosis incidence rate | From enrollment to 28 days after transplantation | The incidence rate of thrombosis during the follow-up period |
| Survival rate | From enrollment to 28 days after transplantation | — |
| Relapse-free survival rate | From enrollment to 28 days after transplantation | — |
| Transplant-related mortality rate | From enrollment to 28 days after transplantation | — |
| Major transplant-related complications | From enrollment to 28 days after transplantation | — |
| Cause of death | From enrollment to 28 days after transplantation | — |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORXiaoyang Yang, MD
Department of Hematology, Haikou People's Hospital
Outcome results
None listed