Ottaviano, G;
Achini-Gutzwiller, F;
Kalwak, K;
Lanino, E;
Faraci, M;
Rao, K;
Chiesa, R;
... Lucchini, G; + view all
(2021)
Impact of in Vivo Lymphodepletion on Outcome in Children with Nonmalignant Disorders Receiving Peripheral Blood Stem Cell Transplantation.
Transplantation and Cellular Therapy
, 27
(12)
1020.e1-1020.e5.
10.1016/j.jtct.2021.08.015.
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Abstract
INTRODUCTION: Peripheral blood stem cell (PBSC) transplantation with in vivo lymphodepletion can provide faster neutrophil recovery with limited risk of severe GvHD in children with non-malignant disorders (NMDs). We aimed to provide an historical comparison between these two strategies for prevalence of GvHD, viral reactivation, timing of immune reconstitution and final outcome. BACKGROUND: METHODS: Data on 98 children receiving PBSC were collected in five European pediatric transplant centers. Only patients with NMDs, receiving treosulfan or myeloablative busulfan conditioning and 9-10/10 HLA-matched transplant were included and divided in two groups according to in vivo lymphodepletion (ATG or alemtuzumab). We compared acute and chronic GvHD, EBV, CMV and ADV reactivations, chimerism, lymphocytes recovery, overall and event free survival. RESULTS: Rate of severe acute GvHD (grade III-IV) was significantly higher in patients receiving ATG (26%; alemtuzumab 10%, p<.05), while viral reactivations occurred with a similar rate in both groups (alemtuzumab 56%, ATG 57%). Alemtuzumab was the major risk factor for delayed T cell immune reconstitution in the first 3 months after transplant (OR 6.0, 95%CI 1.8-19, p<.005). Extended chronic GvHD, adenovirus reactivation, slower CD3+ cells recovery and HLA-mismatch reduced the probability of survival. Infections were the main cause of mortality in our cohort and delayed T cell recovery was significantly associated with mortality in multivariate analysis (OR 12, 95%CI 1.2-114, p<.05). Ultimately, no difference was noted in overall survival and event free survival between ATG and alemtuzumab. CONCLUSION: Both ATG and Alemtuzumab showed a similar impact on outcome of children receiving PBSC for NMDs. Strategies of in vivo lymphodepletion showed specific drawbacks that were counter-balanced by benefits that ultimately lead to a comparable survival rate. A patient-centered planning of lymphodepleting strategy can be advised in children receiving PBSC for NMDs, by favouring T cell recovery in presence of invasive infections or GvHD prevention in high risk mismatched-transplant.
| Type: | Article |
|---|---|
| Title: | Impact of in Vivo Lymphodepletion on Outcome in Children with Nonmalignant Disorders Receiving Peripheral Blood Stem Cell Transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jtct.2021.08.015 |
| Publisher version: | https://doi.org/10.1016/j.jtct.2021.08.015 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Peripheral blood stem cell transplantation; lymphodepletion; ATG; alemtuzumab; GvHD; immune reconstitution. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10133716 |
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