Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors

Abstract

The aim of this study was to identify the risk factors for acute graft-versus-host disease (aGVHD) in children transplanted from a matched-sibling donor (MSD) or an unrelated donor (UD). In all, 87 children consecutively underwent allogeneic bone marrow transplantation (BMT) from MSD (n=36), and UD (n=51). GVHD prophylaxis included CsA alone (n=33) or with MTX (n=51). ATG was added in UD-BMT and thalassemic recipients. CsA whole-blood concentrations were measured by EMIT and the dosing regimen was monitored by Bayesian pharmacokinetic modelling. Trough blood concentration (TBC) during the first 2 weeks post transplantation was lower in children who developed grade II-IV aGVHD than those developing no GVHD or only grade I (57+/-9 vs 94+/-8 ng/ml, P=0.007), whereas peak blood concentration and area under concentration curve vs time were similar in both groups. TBC <85 ng/ml and 'use of MTX' were associated with aGVHD in MSD-SCT (P=0.003 and 0.007, respectively) as well as in UD-SCT (P=0.006 and 0.003). Donor age >or=8 years was significant only in MSD-BMT. Our results have shown the significant decisive role of pharmacological factors such as CSA TBC or use of MTX in the occurrence of GVHD in MSD as well as in UD paediatric BMT.

Matched unrelated bone marrow transplant for T+ combined immunodeficiency

“…Between 45 and 85% of children are reported to develop acute GVHD following MUD BMT, despite various combinations of prophylactic treatments. 32,33 Consistent with these data, 70% of the MUD BMT recipients in our series developed grade II or higher acute GVHD; however, it was transient and in most patients limited to the skin.…”

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

“…This confirms the major role of antithymocyte globulin as part of GvHD prophylaxis in patients transplanted from unrelated donors. 11 We also report a low rate of TRM compared with other series where average TRM reaches 20-25%, 25,29,30,34 even though a large variability (7-45%) is possible. 27,35,38,39 Our results suggest that close monitoring of CsA therapy may permit a substantial reduction of GvHD-related mortality.…”

“…[8][9][10] It is now generally agreed that CsA trough blood concentration (TBC) is the pharmacokinetic parameter that best correlates with GvHD outcome. 11,12 Nevertheless, there are no data regarding specific values of CsA TBC to target to favor mild aGvHD without increasing the incidence of severe GvHD. Based on our previous experience, we have been performing therapeutic drug monitoring of CsA TBC combined with Bayesian dose adjustment, and targeting relatively low levels in leukemia patients.…”

Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A

“…And after conversion from intravenous administration to oral intake, C 5 was not available and only C 0 was measured. CsA concentrations were measured by radioimmunoassay based on monoclonal antibody (RIA) 9 until March 1997 (n ¼ 47), thereafter by fluorescence polarization immunoassay based on monoclonal antibody (M-FPIA) 10 using TDX system according to the manufacturer's instructions (Abbott Japan Co Ltd, Tokyo, Japan) until March 1999 (n ¼ 12).…”

“…1 Previous studies showed that low trough CsA concentration and reduction to less than 80% of the scheduled CsA dose were associated with the onset of grades II-IV acute GVHD. [2][3][4][5] However, these studies did not clarify fully whether low CsA concentrations, after the start of administration, are associated with the onset. Recent study reported that the incidence of grades II-IV acute GVHD was lower in the patients treated with twicedaily infusion of CsA than in those treated with the continuous infusion.…”