RESUMO
BACKGROUND: Despite improvements in first-line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal. OBJECTIVES AND METHODS: We evaluated the feasibility and efficacy of T-cell-replete haploidentical peripheral blood stem cell transplantation (haplo-SCT) with low-dose anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate and prednisolone (PSL) in 14 paediatric patients with high-risk childhood acute leukaemia. RESULTS: All patients achieved complete engraftment. The median time to reaching an absolute neutrophil count of more than 0.5 × 10(9) L(-1) was 14 days. Acute graft-vs-host disease (aGVHD) of grades II-IV and III-IV developed in 10 (71%) and 2 (14%) patients, respectively. Treatment-related mortality and relapse occurred in one (7%) patient and six (43%) patients, respectively. Eleven patients were alive and seven of them were disease-free with a median follow-up of 36 months (range: 30-159 months). The probability of event-free survival after 2 years was 50%. CONCLUSION: These findings indicate that T-cell-replete haplo-SCT, with low-dose ATG and PSL, provides sustained remission with an acceptable risk of GVHD in paediatric patients with advanced haematologic malignancies.
Assuntos
Leucemia/terapia , Transfusão de Linfócitos , Transplante de Células-Tronco , Linfócitos T/transplante , Doença Aguda , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Leucemia/sangue , Leucemia/mortalidade , Contagem de Leucócitos , Masculino , Recidiva , Taxa de SobrevidaRESUMO
Granulocytes were collected by the bag separation method and stored in whole blood for up to 72h. We evaluated the expressions of various surface antigens: CD62L, CD11b, CD18, CD64, CD16b, and CD95. Apoptosis was assessed both by flow cytometry and by light microscopy. Expression levels of all the surface antigens were shown to be maintained during storage for up to 72h. Approximately 80% of granulocytes were annexin V negative until 72h after collection. The storage of granulocyte concentrates collected by the bag separation method may maintain granulocyte surface antigens and lack an apoptotic marker.
Assuntos
Antígenos CD/metabolismo , Apoptose , Preservação de Sangue/instrumentação , Preservação de Sangue/métodos , Granulócitos/citologia , Granulócitos/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7-53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.
Assuntos
Transplante de Células-Tronco , Adolescente , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/terapia , Feminino , Doença Granulomatosa Crônica/terapia , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/terapia , Lactente , Masculino , Imunodeficiência Combinada Severa/terapia , Quimeras de Transplante , Condicionamento Pré-TransplanteRESUMO
The aim of this study was to examine the extended storage of granulocyte concentrates mobilized by granulocyte-colony-stimulating factor (G-CSF) with/without dexamethasone (DEX) and collected by a bag separation method. Ten healthy adult volunteers donated blood three times: twice after granulocyte mobilization by (1) injecting G-CSF at 3 microg kg(-1) subcutaneously (s.c.) and (2) injecting G-CSF at 3 microg kg(-1) s.c. + DEX at 8 mg per oral and once (3) for a baseline control without any forms of mobilization. Granulocytes were collected by a bag separation method. The functions (phagocytosis and oxidative killing levels), viability and levels of interleukin (IL)-1beta, IL-8, IL-6 and tumour necrosis factor-alpha of granulocytes were measured. The average numbers of granulocytes collected from 200-mL samples of whole blood from the G-CSF and G-CSF + DEX groups were 35.1 x 10(8) and 49.4 x 10(8), respectively. Phagocytosis level, oxidative killing level and the viability of the granulocytes mobilized by G-CSF with/without DEX were well maintained for up to 72 h of storage after collection. The levels of the cytokines increased in a time-dependent manner. The in vitro phagocytosis level, oxidative killing level and the viability of granulocytes mobilized by G-CSF with/without DEX and collected by bag separation method can be maintained for as long as 72 h after collection.