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New Treatment Strategy Piloted in Head Start 4 Proves Safe

Tandem transplantation is part of the effort to identify curative, less toxic treatment for young children with malignant brain tumors.

A primary treatment strategy of the new Head Start 4 trial for young patients with malignant central nervous system (CNS) tumors is both safe and feasible, according to a recent study published in Bone Marrow Transplantation.

Tandem cycles of marrow-ablative chemotherapy and autologous hematopoietic cell transplantation — allow for smaller individual doses but a more intense total regimen, says Jonathan Finlay, MB, ChB, FRCP, medical director of Neuro-Oncology at Nationwide Children’s Hospital and senior study author.

“Our hypothesis is that for the highest-risk children, this may result in an improved cure rate and it will be no more toxic, and perhaps less toxic, than other strategies,” says Dr. Finlay, who has been principal investigator in all Head Start trials conducted since 1991. “This study shows that the hypothesis is worthy of further investigation.”

The authors examined the records of 44 young patients who had undergone tandem transplants: 21 with medulloblastoma and other malignant CNS embryonal tumors and 23 with less common malignant brain tumors.

“This may result in an improved cure rate and will be no more toxic – and perhaps less toxic – than other strategies.”

– Jonathan Finlay, MB, ChB, FRCP

Clinicians administered three cycles of intensive chemotherapy to 29 children and only two tandem transplants to 15 patients (for reasons that included insufficient autologous cells for a third transplant).

Among the 27 patients with newly diagnosed disease, progression-free survival was 69.9 ± 9.9 percent and overall survival was 73.5 ± 9.3 percent. The 17 patients who received the regimen after relapse had progression-free survival of 11.8 ± 9.8 percent and overall survival of 15.1 ± 12.3 percent. One patient died of transplant-related toxicity. The mortality rate is similar to that of single transplants used in the Head Start 3 trial.

Head Start 4 is the only trial currently open throughout North America for young children with newly diagnosed malignant brain tumors. Coordinated and hosted by Nationwide Children’s National Experimental Therapeutics (NEXT) Consortium, the trial involves more than 40 institutions worldwide. As part of the trial, children diagnosed with high-risk medulloblastoma and other CNS embryonal tumors are randomly assigned to a traditional single marrow-ablation cycle or tandem cycles.

“One of the concerns in the Head Start trials has been the possible toxicity of transplant,” says Dr. Finlay, who is also a professor of Pediatrics at The Ohio State College of Medicine. “This recently published study, along with the data from the Head Start 3 study, help to justify that this is safe.”

Guerra JA, Dhall G, Marachelian A, Castillo E, Malvar J, Wong K, Sposto R, Finlay JL. Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors. Bone Marrow Transplantation. 2017 Aug 7. [Epub ahead of print]

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