RESUMO
Mesenchymal stromal cells may reverse acute inflammatory disorders. The placenta is important in feto-maternal tolerance. We have used placenta-derived decidua stromal cells (DSCs) to treat graft-versus-host disease and found an immunomodulatory and anti-inflammatory effect. We here report the use of DSCs in two patients with radiculomyelopathy. The first patient was a 73-year old man treated with parotidectomy and irradiation for lymphoma of the neck. Following a Yersinia infection, he developed a radiculomyelopathy in C3/C4 and could not elevate his arms. The second patient was a 34-year old woman who was admitted 8 months after allogeneic hematopoietic stem cell transplantation due to hemolysis, impaired sensorium below arcus, and difficulty in ambulation. Following intravenous infusion of DSCs (1 × 106/kg/infusion), the first patient could elevate his arms to the facial level. He experienced recurrent paralysis after 6 months, and the efficacy of four additional DSC infusions, at subsequent occasions, were limited and transient. The second patient was treated with two doses of DSCs (1 × 106/kg/infusion). After cell infusion, she was able to stand on one leg, sensation in the belly normalized, and she was discharged. These two cases suggest that DSCs may be useful in the treatment of neuroinflammatory disorders.
Assuntos
Decídua/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Placenta/citologia , Radiculopatia/terapia , Doenças da Medula Espinal/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Gravidez , Resultado do TratamentoRESUMO
There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so-called decidua stromal cells (DSCs), are more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients (median age, 49 years; range, 1.6 to 72 years) for grade II-IV acute GVHD. All 21 patients had biopsy-proven gastrointestinal GVHD. The majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days, and 10 were refractory to steroids after >3 days. We used an improved protocol in which DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (range, 0.9 to 2.9)â¯×â¯106 cells/kg body weight with a median of 2 (range, 1 to 6) doses, given 1 week apart. The median viability of thawed DSCs was 93% (range, 69% to 100%), and the median cell passage number was 4 (range, 2 to 4). Complete resolution of GVHD was seen in 11 patients, with a partial response in the other 10. The cumulative incidence of chronic GVHD was 52%. GVHD was mild in 6 patients, moderate in 4 patients, and severe in 1 patient based on National Institutes of Health chronic GVHD severity scoring. Nine patients died, including 3 from relapse and 1 each from acute GVHD and septicemia, Zygomycetes infection, liver insufficiency, cerebral hemorrhage, multiple organ failure, and chronic GVHD with obstructive bronchiolitis. Four-year transplantation-related mortality was 28.6%, and overall survival was 57%. Survival was similar (Pâ¯=â¯.33) to that for all 293 patients who underwent allogeneic hematopoietic cell transplantation during the same period (2012 to 2015), with 66% overall survival. DSC infusion is a novel therapy for acute GVHD grade II-IV, and a randomized trial is currently underway (ClinicalTrials.gov NCT02172937).
Assuntos
Decídua/metabolismo , Doença Enxerto-Hospedeiro/genética , Placenta/metabolismo , Células Estromais/metabolismo , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Gravidez , Estudos Prospectivos , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure. METHODS: We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38). RESULTS: Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05). CONCLUSIONS: The outcome after HSCT for IEM depends on HLA match, year and immune female donor.
Assuntos
Seleção do Doador , Doenças Genéticas Inatas/cirurgia , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Histocompatibilidade , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/mortalidade , Predisposição Genética para Doença , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hereditariedade , Humanos , Lactente , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Doadores não Relacionados , Adulto JovemRESUMO
BACKGROUND/AIMS: Hemorrhagic cystitis (HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). Stromal cells have been tested as therapy for HC. Decidua stromal cells (DSCs) protect the fetus from the mother's immune system. METHODS: Eleven patients with HC of grades 3-4 were treated with DSCs after HSCT. The median age was 33 years (range 8-50), and the median dose of DSCs was 1.5 × 106/kg (range 0.7-2.5). The patients were given 1 dose (1-4). RESULTS: In 5 patients, HC disappeared within 5 days after DSC infusion. Patients who received DSCs within 3 days after the start of HC had a duration of HC of 5 days and a shorter duration of pain than patients who were given DSCs later (p = 0.02). Three patients received DSCs prepared in albumin instead of AB-plasma and tended to have a shorter duration of pain (p = 0.07). There was no infusion toxicity. Adverse events were those often seen after HSCT. Nine of the 11 patients (82%) were alive 1 year after HSCT. CONCLUSIONS: Based on this pilot study, we started a randomized, placebo-controlled double-blind study using 2 doses of 1 × 106 DSCs/kg suspended in albumin for treatment of early HC.
Assuntos
Cistite/etiologia , Cistite/terapia , Decídua/citologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Placenta/citologia , Células Estromais/metabolismo , Células Estromais/transplante , Adolescente , Adulto , Causas de Morte , Criança , Cistite/diagnóstico , Cistite/mortalidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Projetos Piloto , Gravidez , Transplante Homólogo , Adulto JovemRESUMO
Patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) were given the option to be treated at home during the pancytopenic phase. Daily visits by a nurse and phone calls from a physician from the unit were part of the protocol. During almost two decades, 252 patients with haematological malignancies and non-malignant disorders were included. Median age was 47 (range 0-72) years. Myeloablative conditioning was given to 102 patients and reduced intensity to 150. Donors were matched unrelated (n = 160), HLA-identical siblings (n = 71), or HLA-mismatched (n = 21). Cumulative incidence of acute graft-versus-host disease (GVHD) was 35% and that of chronic GVHD was 46%. Non-relapse mortality was 14% 10 years after HSCT. In patients with haematological malignancies (n = 229), the 10-year probability of relapse was 34%. No patients died at home. Overall survival was 59% and relapse-free survival was 50% after 10 years. We conclude that patients treated at home after HSCT have an encouraging long-term outcome.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Serviços de Assistência Domiciliar , Pancitopenia , Complicações Pós-Operatórias , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Antígenos HLA , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto JovemRESUMO
Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9-2.9) × 106 DSCs/kg. The patients were given 2 (1-5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy.