A new study has found that a conditioning regimen containing reduced-dose busulfan, fludarabine, or cyclophosphamide and rabbit anti-thymocyte globulin (rATG) may be effective in achieving engraftment of hematopoietic stem cell transplantation (HSCT) in pediatric patients with nonmalignant disorders such as paroxysmal nocturnal hemoglobinuria (PNH).

The study, published in Pediatric Blood & Cancer, found the regimen to have acceptable toxicity in patients receiving related or unrelated human leukocyte antigen donors.

“Limited data have been published regarding the minimum effective dose of thiotepa required in combination with reduced dose busulfan, fludarabine, and rATG to achieve engraftment in patients undergoing HSCT for nonmalignant disorders,” the authors wrote. “Here, we report on a cohort of six patients with nonmalignant disorders who were treated on a prospective trial and who received a single dose of thiotepa and a reduced/targeted dose of busulfan in combination with fludarabine and rATG.”

The research team assessed 6 pediatric patients with nonmalignant disorders, including 1 patient with PNH at a single center in the United States between June 2018 and January 2021. All underwent fully matched HSCT after a conditioning regimen of a single thiotepa dose of 5 mg/kg combined with reduced dose busulfan, fludarabine, and rATG.

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The study was planned as a dose-escalation study, but there was no need to escalate the dose because all 6 patients achieved engraftment by day 42 and the study was closed.

Toxicities were grade 2 or 3 and were considered acceptable; at 24 months, all patients were considered disease-free. One of the 6 patients developed graft-versus-host disease (GVHD) within 1 year post-transplant, and another, who received stem cells from peripheral blood, developed chronic GVHD.

The authors conclude that the addition of 5 mg/kg of thiotepa to the conditioning regimen led to encouraging disease-free survival in these patients. They recommend avoiding peripheral blood stem cells as a source and implementing intensified GVHD prophylaxis when appropriate.


Fraser A, Castillo P, Cascio E, et al. Feasibility study of busulfan, fludarabine, and thiotepa conditioning regimen for allogeneic hematopoietic stemcell transplantation for children and young adults with nonmalignant disorders. Ped Blood Cancer. Published online April 12, 2023. doi:10.1002/pbc.30322