Impact of serotherapy on immune reconstitution and survival outcomes after stem cell transplantations in children: thymoglobulin versus alemtuzumab.
Biol Blood Marrow Transplant
; 21(3): 473-82, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-25485863
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Hematopoyéticas
/
Acondicionamiento Pretrasplante
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Recuperación de la Función
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Anticuerpos Monoclonales Humanizados
/
Suero Antilinfocítico
/
Antineoplásicos
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Biol Blood Marrow Transplant
Asunto de la revista:
HEMATOLOGIA
/
TRANSPLANTE
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos