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

Abstract

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.

Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation

“…7,15,27,30 T-cell IR has been associated with the use, dose, and timing of serotherapy, indicating that a higher dose of serotherapy shortly before infusion of the graft is detrimental for timely and robust IR. 6,14,27,31,32 Thus, in vivo exposure of graft-infused T cells to serotherapy results in significant depletion of T cells and limits the exceptional proliferative capacity of cord blood T cells, as recently shown. 15 The present study confirms that very low exposure to ATG has a dramatic effect on T-cell reconstitution potential irrespective of disease group, and no exposure to ATG results in exceptional IR potential.…”

Reconstitution of adaptive immunity after umbilical cord blood transplantation: impact on infectious complications

“…However, although some groups observed impaired quantitative B-cell recovery after alloHSCT with ATG (71), others reported higher numbers of circulating B cells in ATG-conditioned patients (35,36). Few studies have assessed the effects of alemtuzumab exposure on circulating B-cell counts after alloHSCT and reported no significant impact (31)(32)(33).…”

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

“…The study of Willemsen et al [9] is a welcome addition to the group of retrospective studies. It showed that, compared with w10 mg/kg ATG (Thymoglobulin, Sanofi, Paris, France), w.8 mg/kg alemtuzumab resulted in a trend toward less acute GVHD, as expected.…”