Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience

Abstract

Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan-or melphalan-based conditioning. Treosulfan causes less venoocclusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children.

Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report

“…The use of treosulfan-based regimens has previously been reported in patients with primary immunodeficiency with few significant short-term toxicities. [19][20][21] It is encouraging to find that treosulfan-containing low-toxicity myeloablative regimens confer improved donor chimerism. In these patients, the goal of any conditioning regimen should be to achieve .50% donor B-lymphocyte chimerism to reliably cease immunoglobulin replacement.…”

Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

“…8,13,14 However, previous experience with treosulfan, fludarabine, and alemtuzumab in HLH was anecdotal. In a series of immunodeficiencies, 3 of 4 HLH patients died, 15 whereas 2 patients in another cohort are long-term survivors. 16 The rate of additional cellular therapy after first HSCT (including second HSCT, administration of DLI, and stem cell boost) was high in the cohort with HLA-mismatched (9/10) donors (86%) while it was only 9% if the donor was HLA-matched (10/10) (P=0.018).…”

Paediatric reduced intensity conditioning: analysis of centre strategies on regimens and definitions by the EBMT Paediatric Diseases and Complications and Quality of Life WP

“…9,23,24 Reduced toxicity is of particular interest in this disease category with a significant proportion of very young children under the age of 1 year. 9,25 A further advantage may be in reducing some of the long-term sequelae of MAC in these children. 9,10 In general FLU-based regimens, mainly in combination with MEL or CY, were the most commonly used.…”

“…TREO was mainly applied for UNSPEC.MAL and haemophagocytic disorders (HPD) where achievement of full donor chimaerism with limited toxicity is crucial. 25 Analysing the various drug combinations within each regimen group, FLU-based regimens revealed the greatest number of different combinations, which may be due to the fact that this was by far the most commonly used regimen category. However, when correlating the number of regimens used with the number of centres we perceived the lowest diversity for FLU.…”