Mark Walters, MD, director of the Pediatric Blood and Marrow Transplant Program at UCSF Benioff Children’s Hospital Oakland, discusses the limitations of standard blood transfusions in pediatric patients with transfusion-dependent beta-thalassemia. 

At a certain point when their hemoglobin falls too low, pediatric patients with transfusion-dependent beta-thalassemia require monthly blood transfusions indefinitely, says Walters. Beyond the inconvenience of monthly trips to the clinic, blood transfusions confer a risk of transfusion-transmitted diseases, such as hepatitis, Walters explains.

Additionally, blood transfusions contain around 200 mg of iron, but since the body can only eliminate 1 to 2 mg of iron per day, patients are required to take iron chelation medications to prevent iron overload, says Walters. Iron overload can poison the liver, pancreas, pituitary gland, and heart, leading to growth deficiencies, liver damage, and eventual heart failure, Walters explains.

In addition, patients require ongoing monitoring for potential toxicities related to blood transfusions and iron chelation, Walters explains. As such, having an alternative option, such as betibeglogene autotemcel (beti-cel; Zynteglo) gene therapy, to transition patients with beta-thalassemia to transfusion-independence is promising, concludes Walters.

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Mark Walters, MD, discusses the limitations of standard blood transfusions in pediatric patients with transfusion-dependent beta-thalassemia.  



Dr. Walters on the Drawbacks of Transfusion Dependence in Pediatric Beta-Thalassemia 

Mark Walters, MD, director of the Pediatric Blood and Marrow Transplant Program at UCSF Benioff Children's Hospital Oakland, discusses the safety profile of betibeglogene autotemcel (beti-cel; Zynteglo) gene therapy in pediatric patients with transfusion-dependent β-thalassemia (TDT), as reported in the phase 3 Northstar-2 and Northstar-3 trials.

All patients enrolled to these trials received myeloablative busulfan conditioning. Due to this, patients experienced complications with busulfan that were concurrent with autologous transplant, such as febrile neutropenia, mucositis, and elevated transaminase levels, Walters says. However, most of these toxicities did not reach grade 3 severity, Walters notes.

Importantly, a serious complication that was observed was veno-occlusive disease of the liver, which occurred in approximately 15% to 20% of patients, Walters explains. This complication, which can occur after busulfan is received, is caused by damage to a particular zone of the liver, leading to liver enlargement, issues with fluid retention, and even renal dysfunction, Walters concludes.

Mark Walters, MD, discusses the safety profile of betibeglogene autotemcel gene therapy in pediatric patients with transfusion-dependent β-thalassemia, as reported in the phase 3 Northstar-2 and Northstar-3 trials.

Mark Walters, MD

Articles

Dr. Walters on the Drawbacks of Transfusion Dependence in Pediatric Beta-Thalassemia

Dr. Walters on the Safety Profile of Beti-Cel in Pediatric Transfusion-Dependent Beta-Thalassemia