Reduced-intensity conditioning in children: a reappraisal in 2008

Abstract

Transplant-related mortality and morbidity (both short and long term) have limited the effectiveness of SCT in children with both malignant and nonmalignant diseases. Reducedintensity preparative regimens permit engraftment of allogeneic cells without many of the toxicities associated with standard TBI-and non-TBI-based conditioning. We review the concepts that underlie reduced-intensity transplantation (RIT) and highlight the experience of the technique in children. Although acute organ damage may be reduced after these transplants, the overall incidence of severe infections and of GvHD may be similar to that seen after standard-intensity transplantation. The relatively small numbers of children who have received RIT and the newness of the technique preclude long-term follow-up with which to monitor the incidence of associated long-term side effects and disease-free survival. Future refinements in RIT and appropriate patient selection for these procedures will hopefully extend its utility in the future.

Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

“…45 Therefore, TRAIL evolves as a promising immunotherapeutic agent, particularly in emerging approaches, to induce graft-versus-tumor reactivity through nonlife-threatening transplantation under nonmyeloablative conditioning. [46][47][48][49] …”

Long-term remission in pediatric Wegener granulomatosis following allo-SCT after reduced-intensity conditioning

“…9 Reduced-intensity conditioning may prevent additional toxic organ damage, but the incidence of GVHD and late complications are still a matter of investigation. 10 In our patient, HLA-identical allo-SCT resulted in 100% donor chimerism, was effective in controlling resistant WG and ensured long-term disease-free survival. However, outcome and quality of life depend on preexisting organ damage, potentially aggravated by GVHD and recurrent infections.…”

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

“…9,25 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. FLU is a highly T-cell toxic drug with a relatively low organ toxicity profile.…”

“…[2][3][4][5][6][7][8] For non-malignant diseases, paediatric RIC-allo-SCT is well established in patients with SAA and Fanconi's anaemia, in primary immunodeficiences and some metabolic disorders. [9][10][11] Regarding the definitions of RIC and non-MAC several workshops and reports have been convened on this issue: first the 'Champlin criteria' were defined followed by further attempts under the sub-auspices of the European Group for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR). Taken together, the majority of published definitions and recommendations consider regimens with FLU ⩽ 180 mg/m 2 , busulfan ⩽ 9 mg/kg, melphalan ⩽ 140 mg/m 2 , thiotepa ⩽ 10 mg/m 2 , CY ⩽ 60 mg/kg and TBI less than 5 Gy as a single fraction or 8 Gy in fractionated doses as RIC.…”