Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.806
Filtrar
1.
Zhonghua Nei Ke Za Zhi ; 58(11): 819-822, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665857

RESUMO

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.


Assuntos
Anemia Aplástica/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/fisiologia , Cordão Umbilical/fisiologia , Doadores não Relacionados , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , China/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Humanos , Células-Tronco Mesenquimais , Células-Tronco de Sangue Periférico , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Cordão Umbilical/imunologia
2.
Epidemiol Mikrobiol Imunol ; 68(2): 71-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398979

RESUMO

INTRODUCTION: The optimal dosage of anti-thymocyte globulin (ATG) may influence the outcome of patients after allogenic haematopoietic stem cell transplantation (HSCT). The aim of our study was to analyse human cytomegalovirus (CMV) infection data, incidence of graft-versus-host disease and other clinical endpoints comparing two patients cohorts that were administered two different Thymoglobuline Genzyme doses as part of the HSCT conditioning regimen. MATERIALS AND METHODS: Total of 65 adult patients received ATG (7.5 mg/kg or 6 mg/kg) as a part of the fludarabine/busulfan/ATG conditioning regimen. CMV DNAemia was monitored after HSCT using quantitative real-time PCR and preemptive treatment was started for viral loads above 1000 cp/ml. RESULTS: The mild ATG dose reduction extended the time to the first CMV detection after transplantation (28 days for 7.5 mg/kg dose vs. 40 days for 6 mg/kg dose, p = 0.04). But it did not reduce the incidence or influence first anti-CMV treatment onset, the initial viral load, peak viral load in whole blood or the antiviral therapy parameters (all p 0.18). No impact of ATG dose reduction on incidence of graft-versus-host-disease, relapse of underlying disease or mortality within first year after transplantation (all p 0.32) were observed. CONCLUSIONS: The reduced ATG dosages can allow lower toxicity of conditioning regimen while keeping the performance.


Assuntos
Soro Antilinfocitário , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adulto , Soro Antilinfocitário/administração & dosagem , Estudos de Coortes , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(29): e16222, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335672

RESUMO

RATIONALE: HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored. PATIENT CONCERNS: A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month. DIAGNOSIS: HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL. INTERVENTIONS: Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation. OUTCOMES: The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection LESSONS:: The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Linfoma de Burkitt , Infecções por HIV , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/complicações , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Intervalo Livre de Doença , Endoscopia Gastrointestinal/métodos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento , Carga Viral/métodos
4.
Expert Opin Pharmacother ; 20(12): 1429-1438, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282759

RESUMO

Introduction: Human cytomegalovirus (HCMV) or human herpesvirus 5 (HHV-5) is a ß-herpesvirus that causes widespread infection in nearly all members of the human population worldwide. Its persistence in humans after primary infection in a latent phase as well as a partial non-protective immune response is the basis for repeated re-activation/re-infection episodes occurring both in immunocompetent and immunocompromised subjects. In the latter patient populations, which include hematopoietic stem cell transplant (HSCT) recipients, HCMV reactivation episodes may be particularly severe, leading to both systemic and end-organ diseases. Since the 90s, at least four antiviral drugs targeting the DNA polymerase complex have been developed for the prevention and treatment of HCMV infections in transplant recipients, used as first-line (ganciclovir and valganciclovir) and second-line therapy (foscarnet and cidofovir). However, due to their toxicity and drug-resistance induction, new drugs with different targets were needed. Areas covered: In 2017, a new drug named letermovir (LTV), which targets the HCMV DNA terminase complex, was licensed for prophylaxis of HCMV infections in HSCT recipients. This is the focus of this review. Expert opinion: LTV safety and efficacy are promising. However, long-term adverse events and the emergence of drug-resistant HCMV strains must be investigated in extended clinical trials prior to drawing final conclusions.


Assuntos
Acetatos/uso terapêutico , Quimioprevenção/métodos , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Quinazolinas/uso terapêutico , Antivirais/uso terapêutico , Quimioprevenção/estatística & dados numéricos , Cidofovir/uso terapêutico , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Farmacorresistência Viral/efeitos dos fármacos , Ganciclovir/uso terapêutico , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Transplantados/estatística & dados numéricos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/estatística & dados numéricos , Valganciclovir/uso terapêutico
5.
Ann Hematol ; 98(8): 1973-1980, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111177

RESUMO

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Linfoma/diagnóstico , Linfoma/terapia , Mucosite/diagnóstico , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , França , Humanos , Linfoma/classificação , Linfoma/mortalidade , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mucosite/patologia , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo
6.
Hematology ; 24(1): 225-231, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31081725

RESUMO

BACKGROUND/OBJECTIVE: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients. METHODS: Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3° at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy. RESULTS: The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor. CONCLUSION: The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco
7.
Lancet Haematol ; 6(5): e239-e253, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30981783

RESUMO

BACKGROUND: Wiskott-Aldrich syndrome is a rare, life-threatening, X-linked primary immunodeficiency characterised by microthrombocytopenia, infections, eczema, autoimmunity, and malignant disease. Lentiviral vector-mediated haemopoietic stem/progenitor cell (HSPC) gene therapy is a potentially curative treatment that represents an alternative to allogeneic HSPC transplantation. Here, we report safety and efficacy data from an interim analysis of patients with severe Wiskott-Aldrich syndrome who received lentiviral vector-derived gene therapy. METHODS: We did a non-randomised, open-label, phase 1/2 clinical study in paediatric patients with severe Wiskott-Aldrich syndrome, defined by either WAS gene mutation or absent Wiskott-Aldrich syndrome protein (WASP) expression or a Zhu clinical score of 3 or higher. We included patients who had no HLA-identical sibling donor available or, for children younger than 5 years of age, no suitable 10/10 matched unrelated donor or 6/6 unrelated cord blood donor. After treatment with rituximab and a reduced-intensity conditioning regimen of busulfan and fludarabine, patients received one intravenous infusion of autologous CD34+ cells genetically modified with a lentiviral vector encoding for human WAS cDNA. The primary safety endpoints were safety of the conditioning regimen and safety of lentiviral gene transfer into HSPCs. The primary efficacy endpoints were overall survival, sustained engraftment of genetically corrected HSPCs, expression of vector-derived WASP, improved T-cell function, antigen-specific responses to vaccinations, and improved platelet count and mean platelet volume normalisation. This interim analysis was done when the first six patients treated had completed at least 3 years of follow-up. The planned analyses are presented for the intention-to-treat population. This trial is registered with ClinicalTrials.gov (number NCT01515462) and EudraCT (number 2009-017346-32). FINDINGS: Between April 20, 2010, and Feb 26, 2015, nine patients (all male) were enrolled of whom one was excluded after screening; the age range of the eight treated children was 1·1-12·4 years. At the time of the interim analysis (data cutoff April 29, 2016), median follow-up was 3·6 years (range 0·5-5·6). Overall survival was 100%. Engraftment of genetically corrected HSPCs was successful and sustained in all patients. The fraction of WASP-positive lymphocytes increased from a median of 3·9% (range 1·8-35·6) before gene therapy to 66·7% (55·7-98·6) at 12 months after gene therapy, whereas WASP-positive platelets increased from 19·1% (range 4·1-31·0) to 76·6% (53·1-98·4). Improvement of immune function was shown by normalisation of in-vitro T-cell function and successful discontinuation of immunoglobulin supplementation in seven patients with follow-up longer than 1 year, followed by positive antigen-specific response to vaccination. Severe infections fell from 2·38 (95% CI 1·44-3·72) per patient-year of observation (PYO) in the year before gene therapy to 0·31 (0·04-1·11) per PYO in the second year after gene therapy and 0·17 (0·00-0·93) per PYO in the third year after gene therapy. Before gene therapy, platelet counts were lower than 20 × 109 per L in seven of eight patients. At the last follow-up visit, the platelet count had increased to 20-50 × 109 per L in one patient, 50-100 × 109 per L in five patients, and more than 100 × 109 per L in two patients, which resulted in independence from platelet transfusions and absence of severe bleeding events. 27 serious adverse events in six patients occurred after gene therapy, 23 (85%) of which were infectious (pyrexia [five events in three patients], device-related infections, including one case of sepsis [four events in three patients], and gastroenteritis, including one case due to rotavirus [three events in two patients]); these occurred mainly in the first 6 months of follow-up. No adverse reactions to the investigational drug product and no abnormal clonal proliferation or leukaemia were reported after gene therapy. INTERPRETATION: Data from this study show that gene therapy provides a valuable treatment option for patients with severe Wiskott-Aldrich syndrome, particularly for those who do not have a suitable HSPC donor available. FUNDING: Italian Telethon Foundation, GlaxoSmithKline, and Orchard Therapeutics.


Assuntos
Terapia Genética , Vetores Genéticos/genética , Células-Tronco Hematopoéticas/metabolismo , Lentivirus/genética , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Criança , Pré-Escolar , Feminino , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Itália , Masculino , Mutação , Linfócitos T/imunologia , Linfócitos T/metabolismo , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Síndrome de Wiskott-Aldrich/sangue , Síndrome de Wiskott-Aldrich/diagnóstico , Proteína da Síndrome de Wiskott-Aldrich/genética
8.
Transplant Proc ; 51(3): 890-895, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979481

RESUMO

Graft-vs-host disease (GVHD) is one of the biggest challenges in haploidentical hematopoietic stem cell transplantation. Antithymocyte globulins (ATGs) are widely used to overcome GVHD, but excessive immunosuppression increases the chances of relapse and infection following transplantation. No defined standard of the appropriate dose of ATG usage is recognized. The study included 11 patients who were treated with a reduced dose of ATG to prevent GVHD in haploidentical hematopoietic stem cell transplantation. A reduced dose of ATG-Thymoglobulin (total dose of 5 mg/kg) was used in the pretreatment protocol for 2 consecutive days. All patients had successful transplantation. The median time of neutrophil engraftment was 12 days. All chimerism tests passed on day 30, 60, and 90 post transplantation. None of the patients had acute GVHD, while only 2 patients had I to II degree chronic GVHD (18.2%). No transplantation-related deaths were observed. The current findings suggest that the reduced dose of ATG can effectively prevent the incidence of acute GVHD in haploidentical hematopoietic stem cell transplantation.


Assuntos
Soro Antilinfocitário/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Guias de Prática Clínica como Assunto , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Transplant Proc ; 51(3): 896-900, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979482

RESUMO

Allogeneic hematopoietic cell transplant (HCT) is a curative procedure for myeloid malignant neoplasms, but relapse after HCT remains critical. A conditioning regimen involving granulocyte colony-stimulating factor-combined high-dose cytarabine, cyclophosphamide, and total body irradiation (G-CSF-combined high-dose cytarabine/cyclophosphamide/total-body irradiation [HDCA/CY/TBI]) was reported to improve outcomes after cord blood transplant (CBT) for myeloid malignant neoplasms, but this regimen was not previously evaluated among patients undergoing bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT). METHODS: We retrospectively analyzed 28 patients who underwent allogeneic HCT including BMT from a related (1 patient) or unrelated donor (9 patients), PBSCT from a related donor (7 patients), or single-unit CBT from an unrelated donor (11 patients) after a G-CSF-combined HDCA/CY/TBI regimen. RESULTS: All patients achieved neutrophil and platelet engraftment, which were significantly more rapid in the BMT/PBSCT group than in the CBT group. Eighteen patients were alive at a median follow-up of 54.3 months. The 3-year relapse and nonrelapse mortality rates were 28.6% and 7.1%, respectively, which were similar between the BMT/PBSCT and CBT groups. Overall survival and disease-free survival at 5 years after HCT were 62.6% and 64.3%, respectively, which were also similar between the BMT/PBSCT and CBT groups. Only disease status at HCT had a significant impact on overall survival and disease-free survival (86.7% with standard risk vs 38.5% with high risk and 86.7% with standard risk vs 38.5% with high risk, respectively). CONCLUSION: A G-CSF-combined HDCA/CY/TBI regimen is a promising conditioning in patients with myeloid malignant neoplasms who undergo not only CBT but also BMT or PBSCT.


Assuntos
Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total/métodos , Adolescente , Adulto , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Doadores não Relacionados , Adulto Jovem
10.
Ann Hematol ; 98(8): 1867-1875, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30993415

RESUMO

Refractory skin ulcers due to severe chronic graft-versus-host disease (cGVHD) remain to be associated with significant morbidity and mortality.We performed an allogeneic donor skin transplantation in seven adult patients after allogeneic hematopoietic stem cell transplantation for cGVHD-associated refractory skin ulcers. While four patients received a split skin graft (SSG), in one patient, a full thickness skin graft for two small refractory ulcers of the ankle was performed, and one patient received in vitro expanded donor keratinocyte grafts derived from hair roots of the original unrelated donor. In one additional patient, a large deep fascial defect of the lower leg was covered with an autologous greater omentum free graft before coverage with an allogeneic SSG. An additional patient was treated with an autologous scrotal skin graft for a refractory ulcer associated with deep sclerosis of cGVHD after unrelated donor transplantation.All skin grafts engrafted and resulted in permanent coverage of the grafted ulcers without any signs of immunological mediated damage. In the patient receiving in vitro expanded keratinocyte grafts, two localized ulcers were permanently covered by donor skin while this approach failed to cover extensive circular ulcers of the lower legs.Allogeneic donor skin grafts are a valuable treatment option in refractory ulcers due to cGVHD but are restricted mainly to related donors while keratinocyte grafts from unrelated donors remain experimental. In male patients lacking a related donor, autologous scrotal skin graft may be an alternative option.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Doença Enxerto-Hospedeiro/cirurgia , Transplante de Células-Tronco Hematopoéticas , Queratinócitos/transplante , Úlcera Cutânea/cirurgia , Condicionamento Pré-Transplante/métodos , Adulto , Doença Crônica , Ciclofosfamida/uso terapêutico , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Imunossupressores/uso terapêutico , Queratinócitos/citologia , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Pele/imunologia , Pele/patologia , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Úlcera Cutânea/terapia , Transplante Autólogo , Transplante Homólogo , Doadores não Relacionados , Irradiação Corporal Total
11.
Drugs ; 79(4): 447-454, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30830601

RESUMO

Intravenous daratumumab (DARZALEX®) is a human CD38 monoclonal antibody approved as combination therapy (with bortezomib, melphalan and prednisone) for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (ASCT). The approval was based on results of the phase 3 ALCYONE trial in which the addition of daratumumab to bortezomib, melphalan and prednisone significantly prolonged median progression-free survival (PFS) relative to bortezomib, melphalan and prednisone alone (primary endpoint). Daratumumab addition was also associated with deeper and durable responses relative to the comparator. The addition of daratumumab did not increase overall toxicity, with the exception of infusion-related reactions and increased rates of infections. The incidences of the most common grade 3 or 4 adverse events in the daratumumab group (neutropenia, thrombocytopenia and anaemia) were largely similar to those in the comparator group. Thus, daratumumab in combination with bortezomib, melphalan and prednisone represents a promising treatment option for patients with NDMM who are ineligible for ASCT.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Transplante de Células-Tronco Hematopoéticas , Humanos , Melfalan/uso terapêutico , Glicoproteínas de Membrana/antagonistas & inibidores , Prednisona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Lancet Haematol ; 6(5): e266-e275, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30910541

RESUMO

BACKGROUND: Retrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial. METHODS: The primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m2 followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m2 per day on days -2 and -1 (total melphalan dose 140 mg/m2), or a melphalan dose of 200 mg/m2 on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178. FINDINGS: Between Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22·6 months (IQR 15·2-47·1) and 20·2 months (IQR 8·8-46·6) in the melphalan alone group. Median progression-free survival was 64·7 months (32·9-64·7) with busulfan plus melphalan versus 43·5 months (19·9-not estimated) with melphalan alone (hazard ratio 0·53 [95% CI 0·30-0·91]; p=0·022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group. INTERPRETATION: These findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma. FUNDING: This study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Bussulfano/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Gradação de Tumores , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Resultado do Tratamento
13.
Am J Case Rep ; 20: 285-289, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30828083

RESUMO

BACKGROUND In the present era, kidney transplantation across immunological barriers (ABO incompatibility and human leucocyte antigen (HLA) incompatibility) is a successful strategy to provide transplantation to immunologically high-risk patients. The safety and outcome of crossing both ABO and HLA barriers simultaneously in a retransplantation scenario is rarely reported from the developing world. CASE REPORT A 30-year-old female underwent a third living donor kidney transplantation. Her previous 2 transplants being lost to chronic allograft nephropathy. The transplantation was done across a simultaneous blood group as well as HLA incompatibility. The donor was the mother who was blood group B, with the recipient being blood group O. The complement dependent cytotoxicity crossmatch of the pair was negative but the flow cross match for T as well as B lymphocytes was positive. The mean fluorescence intensity value for class I antigens was 6951 and that for class 2 antigens was 7534. The patient underwent a desensitization procedure including rituximab, plasmapheresis and intravenous immunoglobulin pre-transplantation. The pre-transplantation isohemaglutunin titer was <1: 8 and the donor specific antibody against class 1 antigens was <2200 and <770 against class 2 antigens. Induction was done with anti-thymocyte globulin in the dose of 3 mg/kg in 2 divided doses. The patient is maintained on triple immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. After a follow-up period of 5 months, she maintains a good graft function with serum creatinine of 1.01 mg/dL. CONCLUSIONS With the advances in the desensitizing procedures in the developing world, kidney transplantation across a combined HLA and ABO incompatible barrier can be offered to these highly sensitized patients, even in case of retransplantation.


Assuntos
Sistema do Grupo Sanguíneo ABO , Incompatibilidade de Grupos Sanguíneos , Antígenos HLA , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/imunologia , Doadores Vivos , Plasmaferese , Reoperação , Rituximab/uso terapêutico , Resultado do Tratamento
16.
Ann Hematol ; 98(6): 1449-1455, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868307

RESUMO

This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)-pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin's lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). Indeed, a lower incidence of chronic GVHD was observed in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant. Despite the low incidence of chronic GVHD, survival was not worse in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non-relapse mortality (NRM) was 24%. In the no BV group, the 3-year PFS was 33%, 3-year OS was 44%, and 3-year NRM was 14%. In chemorefractory patients at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV groups (51% vs. 10%, p = 0.013).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Imunoconjugados/uso terapêutico , Adolescente , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Imunoconjugados/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Pré-Medicação , Intervalo Livre de Progressão , Estudos Retrospectivos , Terapia de Salvação , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
17.
Clin Lab Med ; 39(1): 157-169, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30709504

RESUMO

It is increasingly recognized that calcineurin inhibitors (CNI) such as cyclosporine and tacrolimus are not ideal immunosuppressive agents. Side effects, including increased rates of infection, hypertension, and malignancy, can be severe. Thus, in the past decade, there has been much focus on the development of novel therapeutic agents and strategies designed to replace or minimize CNI exposure in transplant patients. This article reviews potential novel targets in T cells, alloantibody-producing B cells, plasma cells, and complement in transplantation.


Assuntos
Imunossupressão/métodos , Transplante , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Fatores Imunológicos/uso terapêutico , Modelos Imunológicos , Linfócitos T/fisiologia , Condicionamento Pré-Transplante/métodos
18.
Crit Rev Oncol Hematol ; 133: 112-119, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30661647

RESUMO

Several findings suggest that the pathogenesis and clinical history of myelodysplastic syndromes (MDS) is influenced by a variety of immune pathways and mechanisms. Coherently several therapeutic approaches based on the idea of modulating the immune system have been exploited in this clinical setting. The present review will first consider more consolidated strategies such as antithymocyte globulin and immunomodulatory (IMiDs) analogues. Less explored approaches, such as anti tumor necrosis factor antibodies, cyclosporin and bortezomib will be also evaluated. Finally the potential impact of anti-tumour vaccination or hemopoietic cell transplantation on the outcome of MDS patients will be addressed.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Sistema Imunitário/fisiopatologia , Imunomodulação/fisiologia , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/terapia , Vacinação/métodos , Vacinas Anticâncer/uso terapêutico , Humanos , Sistema Imunitário/efeitos dos fármacos , Agonistas Mieloablativos/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos
19.
Ann Hematol ; 98(3): 753-762, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30617644

RESUMO

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Aloenxertos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Doadores não Relacionados
20.
Pediatr Transplant ; 23(2): e13358, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30687992

RESUMO

Aerosolized ribavirin has been used in pediatric immunocompromised patients to treat acute respiratory viral infections, but oral ribavirin may be a less expensive alternative that allows for outpatient therapy. Oral ribavirin has compared favorably to aerosolized ribavirin in adult studies, but data on safety are lacking in pediatric populations. Four cases are described in which oral ribavirin was used to treat viral respiratory infections in recipients of allogeneic hematopoietic stem cell transplants at a Children's Hospital, demonstrating safety and feasibility.


Assuntos
Alemtuzumab/efeitos adversos , Antivirais/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Infecções por Paramyxoviridae/tratamento farmacológico , Ribavirina/administração & dosagem , Condicionamento Pré-Transplante/efeitos adversos , Administração Oral , Alemtuzumab/uso terapêutico , Antivirais/uso terapêutico , Criança , Quimioterapia Combinada , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Lactente , Masculino , Infecções por Paramyxoviridae/imunologia , Ribavirina/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA