Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.
Cytotherapy
; 19(6): 735-743, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28395942
ABSTRACT
BACKGROUND:
T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 104/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 107/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT.METHODS:
Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy).RESULTS:
Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse.CONCLUSIONS:
Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Transplante de Células-Tronco Hematopoéticas
/
Neoplasias Hematológicas
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article