RESUMO
Twenty-three children with nonmalignant disorders received HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after ex vivo elimination of αß(+) T cells and CD19(+) B cells. The median number of CD34(+), αß(+)CD3(+), and B cells infused was 16.8 × 10(6), 40 × 10(3), and 40 × 10(3) cells/kg, respectively. No patient received any posttransplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD). All but 4 patients engrafted, these latter being rescued by a second allograft. Three patients experienced skin-only grade 1 to 2 acute GVHD. No patient developed visceral acute or chronic GVHD. Cumulative incidence of transplantation-related mortality was 9.3%. With a median follow-up of 18 months, 21 of 23 children are alive and disease-free, the 2-year probability of disease-free survival being 91.1%. Recovery of γδ(+) T cells was prompt, but αß(+) T cells progressively ensued over time. Our data suggest that this novel graft manipulation strategy is safe and effective for haplo-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
Assuntos
Linfócitos B , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Depleção Linfocítica , Receptores de Antígenos de Linfócitos T alfa-beta , Linfócitos T , Aloenxertos , Antígenos CD/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: It is unclear whether there is a causative relationship between the development of metabolic syndrome (MS) and increased risk of early cardiovascular morbidity in patients receiving hematopoietic stem cell transplantation (HSCT) during childhood. Early identification of risk factors associated with insulin resistance, MS, and abnormal glucose tolerance during childhood or adolescence in these patients could represent a useful tool for preventing cardiovascular disorders. PROCEDURE: In a single-center, prospective, descriptive, cross-sectional study, we studied 45 survivors of hematological malignancies (age: 13.9 ± 4.8 years) treated with HSCT before the age of 18 years and 90 matched healthy controls. We collected clinical, imaging, and laboratory data including oral glucose tolerance test (OGTT). RESULTS: 7/45 patients (15.6%) showed abnormal glucose tolerance at OGTT, 1/45 (2.2%) was obese, and none fulfilled the criteria for MS. A waist/height ratio >0.5 was associated with patients with abnormal glucose tolerance (85.7% of cases), compared to patients with normal glucose tolerance (42.1%) and controls (23.3%). In patients with abnormal glucose tolerance, use of total body irradiation (TBI) as conditioning regimen was more common, and time elapsed from HSCT was longer. CONCLUSIONS: Patients treated with HSCT may develop insulin resistance early after transplantation. They do not show overt obesity, but have redistribution of fat tissue with central fat accumulation. The main factors associated with increased metabolic risk are TBI and time from HSCT. Evaluation of MS and glucose tolerance should be part of hormonal follow-up, which should be routinely proposed to these patients.
Assuntos
Distribuição da Gordura Corporal , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Resistência à Insulina , Síndrome Metabólica/epidemiologia , Sobreviventes/estatística & dados numéricos , Adolescente , Antropometria , Peso Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Causalidade , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Progressão da Doença , Feminino , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hormônios/sangue , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Lactente , Masculino , Síndrome Metabólica/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Estudos Prospectivos , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversosRESUMO
BACKGROUND: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-αß/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition. METHODS: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 'poor mobilizers' (PM) failing to attain ≥40 CD34+ HSCs/µL after 4 daily G-CSF doses and/or with predicted apheresis yields ≤12.0x106 CD34+ cells/kg recipient's body weight. RESULTS: MZ significantly increased CD34+ counts in PM. Naïve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16+ monocytes and the down-regulation of IFN-γ production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs. CONCLUSIONS: MZ facilitates the collection of mega-doses of CD34+ HSCs for haploidentical HSCT, while affecting graft composition.
Assuntos
Doenças Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Compostos Heterocíclicos/administração & dosagem , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Doadores de Tecidos , Aloenxertos , Antígenos CD19/metabolismo , Antígenos CD34/metabolismo , Benzilaminas , Tipagem e Reações Cruzadas Sanguíneas , Contagem de Células , Criança , Ciclamos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doenças Hematológicas/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/fisiologia , HumanosRESUMO
We report on the successful infusion of human adenovirus (HAdV)-specific T cells in a child with congenital amegakaryocytic thrombocytopenia, given T-cell-depleted hematopoietic stem cell transplantation (HSCT) from the HLA-haploidentical mother during extracorporeal membrane oxygenation (ECMO) for severe HAdV-related respiratory failure. Donor-derived, interferon (IFN)-γ-secreting HAdV-specific T cells were enriched using the cytokine capture assay, after in vitro stimulation with overlapping peptides from the immunodominant HAdV5 hexon protein. Two weeks after T-cell transfer, viral load decreased and ECMO was discontinued. T-cell responses to HAdV antigens were documented after four weeks and were associated with viral clearance, immune reconstitution and clinical amelioration.
Assuntos
Infecções por Adenovirus Humanos/terapia , Proteínas do Capsídeo/imunologia , Oxigenação por Membrana Extracorpórea , Imunoterapia Adotiva , Síndrome do Desconforto Respiratório/terapia , Transplante de Células-Tronco/efeitos adversos , Linfócitos T/imunologia , Trombocitopenia/complicações , Infecções por Adenovirus Humanos/etiologia , Adenovírus Humanos/imunologia , Criança , Síndrome Congênita de Insuficiência da Medula Óssea , Humanos , Interferon gama/metabolismo , Depleção Linfocítica , Masculino , Fragmentos de Peptídeos/imunologia , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Linfócitos T/virologia , Trombocitopenia/imunologia , Trombocitopenia/terapia , Transplante Homólogo , Carga ViralRESUMO
Extracorporeal photopheresis (ECP) is broadly used in adults with cutaneous T-cell lymphoma, acute or chronic graft-versus-host disease (GVHD), rejection of solid organ transplants, and a variety of autoimmune, cell-mediated diseases. The predominant use of ECP in children and adolescents is for treating GVHD. Children pose specific challenges to ECP, due to their unique physiology and to patient's size. Herein, we will focus on current clinical trials with ECP in children with GVHD, with an emphasis on technical and clinical issues that are peculiar to the paediatric setting.
Assuntos
Rejeição de Enxerto/terapia , Doença Enxerto-Hospedeiro/terapia , Transplante de Órgãos , Fotoferese/métodos , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/terapia , MasculinoRESUMO
Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo)-related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse.