Antibodies to anti-thymocyte globulin in aplastic anemia patients have a negative impact on hematopoietic SCT

Zijde, Cornelia M. Jol–van der; Bredius, Robbert G. M.; Jansen-Hoogendijk, Anja M.; Smiers, Frans J.; Lankester, Arjan C.; Tol, Maarten J.D. van

doi:10.1038/bmt.2011.259

Cited by 6 publications

(1 citation statement)

References 12 publications

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“…This translated into a lower incidence of aGVHD but also into higher risks of overall mortality, treatment failure, and relapse of the original disease in children with different benign and malignant diseases. Despite these results, the use of alemtuzumab is still recommended in patients who received ATG treatment before because of the risks of sensitization and antibody formation against ATG [12,39]. Our data are also the first to connect the length of lympholytic drug exposure to immune recovery and outcome after HSCT in children: longer drug exposure delayed the T cell recovery in both ATG-and alemtuzumab-treated patients.…”

Section: Discussioncontrasting

confidence: 55%

Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab

Willemsen

Zijde

Admiraal

et al. 2015

Biology of Blood and Marrow Transplantation

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The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is strongly affected by the kinetics of reconstitution of the immune system. This study compared the effects of antithymocyte globulin (ATG) and alemtuzumab on various outcome parameters after HSCT. The study cohort consisted of 148 children, with a median age of 9.6 years (range, .4 to 19.0), who underwent HSCT for malignant and benign hematological disorders in a single HSCT unit. Conditioning included ATG (n = 110) or alemtuzumab (n = 38). Cox proportional hazard regression analysis showed that alemtuzumab significantly delayed the recovery of CD3(+) T cells and CD4(+)as well as CD8(+) T cell subsets (P ≤ .001) and natural killer (NK) cells (P = .008) compared with ATG. In both ATG- and alemtuzumab-treated patients, shorter drug exposure lead to significantly faster recovery of T cells. Alemtuzumab was associated with lower donor chimerism 3 and 6 months after transplantation and a higher risk of disease relapse (P = .001). The overall survival and event-free survival risks were significantly lower for alemtuzumab-treated patients (P = .020 and P < .001, respectively). Patients who received alemtuzumab showed a trend to lower risk of acute graft-versus-host disease, more human adenovirus, and less Epstein-Barr virus reactivations compared with patients who received ATG. These data indicate that children treated with alemtuzumab as part of the conditioning regimen have a slower T cell and NK cell reconstitution compared with those treated with ATG, which compromises the overall and event-free survival. Prolonged length of lympholytic drug exposure delayed the T cell recovery in both ATG- and alemtuzumab-treated patients. Therefore, we recommend detailed pharmacokinetic/pharmacodynamic (PK/PD) analyses in a larger cohort of patients to develop an algorithm aiming at optimization of the serotherapy containing conditioning regimen.

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Section: Discussioncontrasting

confidence: 55%