TY - JOUR
T1 - Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children
T2 - Thymoglobulin Versus Alemtuzumab
AU - Willemsen, Laura
AU - Jol-van der Zijde, Cornelia M.
AU - Admiraal, Rick
AU - Putter, Hein
AU - Jansen-Hoogendijk, Anja M.
AU - Ostaijen-ten Dam, Monique M.
AU - Wijnen, Juul T.
AU - van Kesteren, Charlotte
AU - Waaijer, Jacqueline L M
AU - Lankester, Arjan C.
AU - Bredius, Robbert G M
AU - van Tol, Maarten J D
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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 recoveryof 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- andalemtuzumab-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.
AB - 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 recoveryof 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- andalemtuzumab-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.
KW - Alemtuzumab
KW - Antithymocyte globulin
KW - Children
KW - Hematopoietic stem cell transplantation
KW - Immune reconstitution
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84922815129&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2014.11.674
DO - 10.1016/j.bbmt.2014.11.674
M3 - Article
C2 - 25485863
AN - SCOPUS:84922815129
SN - 1083-8791
VL - 21
SP - 473
EP - 482
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -