RESUMO
Treatments of aplastic anemia comprise supportive therapy and aplastic anemia-specific therapy to recover from hematopoiesis. Supportive therapy includes transfusion, granulocyte colony-stimulating factor, and iron chelation therapy in addition to symptomatic treatment. Aplastic anemia-specific treatments that aim to achieve hematopoietic recovery are immunosuppressive therapy, thrombopoietin receptor agonist (TPO-RA) treatment, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although the transplantation achieves complete recovery of hematopoiesis (healing), there is a risk of death from transplant-related complications. The most effective drug therapy is the combination of TPO-RA and the immunotherapy combined with anti-thymocyte globulin and cyclosporine. This treatment is also effective against secondary, drug-induced, or hepatitis-associated aplastic anemia. In the treatment of aplastic anemia, the treatment choice is made based on the disease severity and patient ages.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos , HumanosRESUMO
Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta Imunológica , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Histocompatibilidade , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Infecções/etiologia , Infecções/mortalidade , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Linfócitos T/imunologia , Doadores não RelacionadosRESUMO
Application of anti-thymocyte globulin (ATG) is a widely used strategy for the prevention of graft-versus-host disease (GvHD). As vitamin D3 serum levels are also discussed to affect hematopoietic stem cell transplantation (HSCT) outcome and GvHD development, we analysed a possible interplay between ATG treatment and serum levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in 4 HSCT cohorts with different vitamin D3 supplementation. ATG is significantly associated with higher serum level of 1,25-dihydroxyvitamin D3 around HSCT (day -2 to 7, peri-transplant), however only in patients with adequate levels of its precursor 25-hydroxyvitamin D3. ATG exposure had no impact on overall survival in patients supplemented with high dose vitamin D3, but was associated with higher risk of one-year treatment-related mortality (log rank test p=0.041) in patients with no/low vitamin D3 supplementation. However, the difference failed to reach significance applying a Cox-model regression without and with adjustment for baseline risk factors (unadjusted P=0,058, adjusted p=0,139). To shed some light on underlying mechanisms, we investigated the impact of ATG on 1,25-Dihydroxyvitamin D3 production by human dendritic cells (DCs) in vitro. ATG increased gene expression of CYP27B1, the enzyme responsible for the conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3, which was accompanied by higher 1,25-dihydroxyvitamin D3 levels in ATG-treated DC culture supernatants. Our data demonstrate a cooperative effect of 25-hydroxyvitamin D3 and ATG in the regulation of 1,25-dihydroxyvitamin D3 production. This finding may be of importance in the context of HSCT, where early high levels of 1,25-dihydroxyvitamin D3 levels have been shown to be predictive for lower transplant related mortality and suggest that vitamin D3 supplementation may especially be important in patients receiving ATG for GvHD prophylaxis.
Assuntos
Soro Antilinfocitário/uso terapêutico , Biomarcadores , Calcifediol/sangue , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Soro Antilinfocitário/farmacologia , Estudos de Coortes , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Estimativa de Kaplan-Meier , Monócitos/imunologia , Monócitos/metabolismo , Prognóstico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. METHODS: Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. CONCLUSION: These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.
Assuntos
Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/terapia , Doadores não Relacionados , Adolescente , Adulto , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Terapia Combinada , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Histocompatibilidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Recidiva , Indução de Remissão , Estudos Retrospectivos , Adulto JovemAssuntos
Acetilcisteína/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Hepatite/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunossupressores/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Resistência a Medicamentos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/uso terapêutico , Hepatite/diagnóstico , Hepatite/imunologia , Humanos , Melanoma/imunologia , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do TratamentoRESUMO
Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P =03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Doença Aguda , Adolescente , Adulto , Idoso , Causas de Morte , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Indução de Remissão , Fatores de Risco , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Adulto JovemRESUMO
HLA 1-locus-mismatched unrelated donors (1MMUD) are used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. Here we retrospectively reviewed 3,313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD in 2009-2014. We compared the outcomes of MUD (nï¼2,089) and 1MMUD with antithymocyte globulin [ATG; 1MM-ATG (ï¼) ; nï¼109] with those of 1MMUD without ATG [1MM-ATG (-) ; nï¼1,115]. In the 1MM-ATG (ï¼) group, the median total dose of ATG (thymoglobulin) was 2.5 (range, 1.0-11.0) mg/kg. The rates of grade III-IV acute GvHD, non-relapse mortality (NRM), and overall mortality were significantly lower in the MUD group than in the 1MM-ATG (-) group [hazard ratio (HR) 0.77; Pï¼0.016; HR, 0.74, P<0.001; and HR, 0.87, Pï¼0.020, respectively]. Similarly, the rates of grade III-IV acute GvHD, NRM, and overall mortality were significantly lower in the 1MM-ATG (ï¼) group than in the 1MM-ATG (-) group (HR, 0.42, Pï¼0.035; HR, 0.35, P<0.001; and HR, 0.71, Pï¼0.042, respectively). Even in the recent cohort, the outcome of allo-HCT from 1MM-ATG (-) was inferior to that of allo-HCT from MUD. Nevertheless, the negative impact of 1MMUD disappeared with the use of low-dose ATG without exacerbating the risk of relapse.
Assuntos
Soro Antilinfocitário/uso terapêutico , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Doença Enxerto-Hospedeiro , Humanos , Estudos Retrospectivos , Transplante HomólogoRESUMO
BACKGROUND: Resistant cytomegalovirus (R-CMV) is an emerging problem in the renal transplantation population. The most frequent CMVs are high-resistance mutations (UL97 gene). METHODS: We describe our experience in management of R-CMV after renal transplant at our center (2012-2016). RESULTS: We encountered 3 cases of R-CMV infection after renal transplant (all primary infections). All 3 patients received induction therapy with corticosteroids, tacrolimus, and mycophenolate mofetil. The first patient (basiliximab induction, preemptive CMV) developed CMV replication on day +53, which responded poorly both to standard-dose valganciclovir (vGCV) and high-dose ganciclovir (GCV) (creatinine clearance [CrCl] >70 mL/min; vGCV 900 mg twice daily for 50 days and GCV 7.5 mg/kg twice daily for 8 days). Hematologic toxicity occurred. The R-CMV test was positive and foscarnet (FOS) was initiated (90 mg/kg twice daily for 21 days). The second patient presented CMV infection (day +30, thymoglobulin induction, CMV prophylaxis), which was not controlled with the high dose (CrCl 23 mL/min; GCV 3.5 mg/kg twice daily and vGCV 900 mg twice daily), resulting in severe neutropenia. R-CMV was detected and FOS initiated (FOS 50 mg/kg twice daily for 7 days and 50 mg/kg every 2 days for 13 days). The third patient's infection occurred on day +22 (basiliximab induction, preemptive CMV). Standard-dose vGCV was uneffective (CrCl >70 mL/min, vGCV 900 mg twice daily) and it did not respond to the high dose (GCV 7.5 mg/kg twice daily and vGCV 2700 mg/d). Moderate hematologic toxicity occurred. R-CMV was diagnosed and FOS treatment begun (FOS 70 mg/kg per day for 2 weeks). CONCLUSIONS: Resistant CMV infection may be severe due to viral infection and side effects of high-dose antiviral treatment. We presented 3 cases requiring the use of FOS in the absence of response or toxic effects from the usual treatment, with an optimal sustained response (temporary in case 2) and without serious side effects.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Farmacorresistência Viral Múltipla , Feminino , Foscarnet/uso terapêutico , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Complicações Pós-Operatórias/virologia , Proteínas Recombinantes de Fusão/uso terapêutico , Tacrolimo/uso terapêutico , Valganciclovir , Replicação Viral/efeitos dos fármacosRESUMO
The use of monoclonal antibody targeted therapy has changed the management of several diseases, including in hematology and immunology. The panel of the present available biotherapies allows a specific action at various stages of the immune response. Indeed, some of these molecules can target the naive T cell at the immunological synapse or the way of TH1, TH17 and regulatory T cell. Others may be more specific for the B cell and immunoglobulin. Some will even be active on both B and T cells.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Terapia Biológica/métodos , Sistema Imunitário/efeitos dos fármacos , Anticorpos Monoclonais/farmacologia , Soro Antilinfocitário/uso terapêutico , Doenças Autoimunes/terapia , Humanos , Sistema Imunitário/fisiopatologia , Sinapses Imunológicas/efeitos dos fármacos , Imunomodulação , Terapia de Alvo Molecular , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
The purpose of this study was to investigate the effects of rabbit antihuman thymocyte globulin (R-ATG) and Jurkat cell-reactive anti-T lymphocyte globulin (ATG-F) in the treatment of childhood aplastic anemia (AA) and compare their efficacy and side effects. A total of 53 children with AA were analyzed in the present study, including 32 cases of severe AA, 10 cases of very severe AA and 11 cases of transfusion-dependent nonsevere AA. While receiving immunosuppressive therapy (IST), 29 and 24 patients, all of whom received long-term oral supplement with cyclosporin A (CSA), androgen, and traditional Chinese medicines, were treated with R-ATG and ATG-F, respectively. If necessary, the patients were also given supportive care such as component transfusion and/or infection control. Absolute counts of peripheral blood lymphocyte at various time points were dynamically measured after ATG therapy. According to the International AA Treatment and Effect standards, we found that there were no statistically significant differences in the response rate (70.83% vs. 68.97%, p > 0.05) and the overall survive rate (83.33% vs. 82.76%, p > 0.05) between the ATG-F and R-ATG groups. In addition, no obvious differences were observed between these two groups in the response time, efficacy in severe AA and very severe AA, or the incidence rates of ATG-related adverse reactions. After ATG treatment, the extent of peripheral blood lymphocyte reduction and duration in peripheral blood were similar between the ATG-F and R-ATG groups. The results of this study showed that ATG-F and R-ATG had similar efficacy and adverse reactions in the first-line treatment of childhood AA, despite being derived from different immunogens.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Células Jurkat/imunologia , Linfócitos T/imunologia , Anemia Aplástica/tratamento farmacológico , Animais , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Imunoterapia , Contagem de Linfócitos , Masculino , Medicina Tradicional Chinesa , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.
Assuntos
Anemia Aplástica/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Alemtuzumab , Células da Medula Óssea/citologia , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Irmãos , Doadores de Tecidos , Resultado do Tratamento , Reino Unido , Adulto JovemRESUMO
BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.
Assuntos
Enterococcus faecium/isolamento & purificação , Rejeição de Enxerto/prevenção & controle , Infecções por Bactérias Gram-Positivas/epidemiologia , Imunossupressores/uso terapêutico , Transplante de Órgãos , beta-Lactamas/uso terapêutico , Adulto , Fatores Etários , Idoso , Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab , Estudos de Coortes , Enterococcus/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Transplante de Coração , Humanos , Transplante de Rim , Transplante de Fígado , Transplante de Pulmão , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Resistência às Penicilinas , Penicilinas , Estudos Prospectivos , Proteínas Recombinantes de Fusão/uso terapêutico , Fatores de Risco , Suíça , Resultado do Tratamento , Vancomicina , Resistência a VancomicinaRESUMO
A 62-year-old man with transfusion-dependent severe aplastic anemia received immunosuppressive therapy (IST) with rabbit antithymocyte globulin and cyclosporine A in April 2010. However, his transfusion dependency did not improve. As more than 100 red blood cell (RBC) transfusions had been performed, he was administered iron chelation therapy (ICT) with deferasirox (DFX) to improve iron overload starting in July 2011. Consequently, both RBC and platelet transfusion dependency gradually improved concomitant with a decrease in serum ferritin. The bone marrow (BM) biopsy findings before administration of DFX showed severe iron accumulation and strong positive immunostaining for 8-OHdG, a marker of oxidative stress due to free iron. One year after ICT, the number of BM hematopoietic cells was increased and both iron deposition and oxidative stress were decreased. These findings suggest that DFX may contribute to hematological improvement in patients with IST-refractory aplastic anemia.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Benzoatos/uso terapêutico , Transfusão de Sangue , Quelantes de Ferro/uso terapêutico , Triazóis/uso terapêutico , Anemia Aplástica/etiologia , Transfusão de Sangue/métodos , Ciclosporina/uso terapêutico , Deferasirox , Humanos , Masculino , Pessoa de Meia-Idade , Reação Transfusional , Resultado do TratamentoRESUMO
UNLABELLED: Although high-dose cyclophosphamide seems to achieve durable complete remission, there are still concerns about its too much early toxicity. So, we designed a clinical study to investigate the effects of high-dose cyclophosphamide/ATG combined with cord blood infusion as first-line therapy for patients with severe aplastic anemia. PATIENTS AND METHOD: Between January 2003 and September 2007, we treated 16 treatment-naive patients with severe aplastic anemia with cord blood infusion after high-dose cyclophosphamide (50 mg/kg/d × 2) and rabbit antithymocyte globulin (3 mg/kg/d × 5) therapy. RESULTS: Although only one patient had durable full donor engraftment, 14 of the enrolled 16 patients had rapid autologous hematopoietic recovery. The median recovery time for neutrophils and platelets was only 23 and 37 d after infusion of cord blood. Of the 15 responding patients, all patients achieved treatment-free remission: nine patients met the criteria for a complete remission; six patients achieved a partial remission. CONCLUSION: Infusion of cord blood after high-dose cyclophosphamide/ATG resulted in a rapid autologous hematologic recovery and a high response rate in patients with treatment-naive patients with severe aplastic anemia. These promising results merit further investigation and confirmation on a larger number of patients.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Transfusão de Sangue Autóloga , Ciclofosfamida/uso terapêutico , Sangue Fetal/transplante , Hematopoese , Imunossupressores/uso terapêutico , Adolescente , Adulto , Anemia Aplástica/mortalidade , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Resultado do Tratamento , Adulto JovemAssuntos
Doença Enxerto-Hospedeiro/cirurgia , Transplante de Células-Tronco Mesenquimais , Doença Aguda , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Daclizumabe , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/uso terapêutico , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Infecções/etiologia , Infliximab , Estimativa de Kaplan-Meier , Terapia PUVA , Fotoferese , Estudos Retrospectivos , Rituximab , Sirolimo/uso terapêutico , Linfócitos T/imunologia , Transplante Homólogo , Falha de Tratamento , Resultado do TratamentoRESUMO
Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h, rATG was administered during brain death (10mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88±0·22 mg/dl; BD, 1·37±0·07 mg/dl; and BD+rATG, 0·64±0·02 mg/dl (BD versus BD+rATG, P<0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25±0·5 versus BD, 4·75±0·5, P<0·01; BD+rATG, 2·75±0·5 versus BD 4·75±0·5 P<0·01). Gene expression was evaluated with reverse transcription-polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P<0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32±7·5 versus BD: 129±18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.
Assuntos
Soro Antilinfocitário/uso terapêutico , Morte Encefálica/imunologia , Imunossupressores/uso terapêutico , Transplante de Rim , Rim/patologia , Linfócitos T , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodos , Animais , Apoptose , Quimiocina CCL2/sangue , Isquemia Fria , Creatinina/sangue , Citocinas/biossíntese , Citocinas/genética , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/irrigação sanguínea , Rim/imunologia , Masculino , Necrose , Infiltração de Neutrófilos , Peroxidase/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Respiração Artificial , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Ureia/sangueRESUMO
We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.
Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Doadores não Relacionados , Adolescente , Soro Antilinfocitário/uso terapêutico , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Lactente , Estimativa de Kaplan-Meier , Masculino , Infecções Oportunistas/etiologia , Recidiva , Estudos Retrospectivos , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Falha de Tratamento , Resultado do TratamentoRESUMO
Aplastic anaemia (AA) is a rare heterogeneous condition in children. 15-20% of cases are constitutional and correct diagnosis of these inherited causes of AA is important for appropriate management. For idiopathic severe aplastic anaemia, a matched sibling donor (MSD) haematopoietic stem cell transplant (HSCT) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. IST with horse anti-thymocyte globulin (ATG) is superior to rabbit ATG and has good long-term results. In contrast, IST with rabbit ATG has an overall response of only 30-40%. Due to improvements in outcome over the last two decades in matched unrelated donor (MUD) HSCT, results are now similar to that of MSD HSCT. The decision to proceed with IST with ATG or MUD HSCT will depend on the likelihood of finding a MUD and the differing risks and benefits that each therapy provides.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Doadores Vivos , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Cavalos , Humanos , Lactente , Masculino , Coelhos , Irmãos , Transplante HomólogoRESUMO
OBJECTIVE: To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on severe aplastic anemia (SAA). METHODS: Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM between 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. RESULTS: Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respectively 98.6%, 97.3%, 97.3%, 67.5%, and median survival time was 180 months. Compared to the conditions before administering the medication of ATG/ ALG plus KNCM, after 2 weeks, reticulocyte was first improved (P = 0.001); one month later, followed by palette (P = 0.037); two months later, by neutrophil cell in peripheral blood (P = 0.001); three months later, then by the hemoglobin (P = 0.012). By conducting 1-year follow-up, 1 case of complication--paroxysmal nocturnal hemoglobinuria (PNH) was identified and the patient still alive today. CONCLUSION: ATG/ALG plus KNCM had better effect on SAA and could improve patients' survival rate.
Assuntos
Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Anemia Aplástica/mortalidade , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To explore the prognostic factors for very severe aplastic anemia (VSAA) patients treated mainly with Chinese Kidney (Shen)-invigorating drugs (CKID) combined with anti-lymphocyte globulin (ALG) or anti-thymocyte globulin (ATG). METHODS: Twenty-seven VSAA patients were treated with CSID+ALG/ATG therapy in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The relationship of the effectiveness and some factors (age of patients, course of illness, blood and bone marrow figures, etc.) were analyzed. RESULTS: In the 25 evaluated VSAA patients who had been followed up for over 1 year, 9 patients (36.0%) were basically cured, 5 (20.0%) remitted, 6 (24.0%) were markedly improved, and 5 (20.0%) were treated in vain, with the total effective rate of treatment being 80.0% (20/25). Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA, of male sex (P=0.037), >20 years old (P=0.045), with an illness course [Symbol: see text] month (P=0.048), with peripheral neutrophil count >0.1 × 10(9)/L (P=0.023), and with reticulocyte count >10 × 10(9)/L (P=0.002). Platelet count (P=0.620) and bone marrow lymphocyte percentage (P=0.736) showed no correlation with the therapeutic effectiveness. Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients > 20 years old, with peripheral neutrophil count [Symbol: see text] 0.1 × 10(9)/L, reticulocyte count [Symbol: see text]10 × 10(9)/L, and platelet count > 10 × 10(9)/L (all P=0.0001). Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application (from onset of the illness) showed no significant influence on patients' survival time (P=0.085 and P=0.935, respectively). CONCLUSIONS: CSKD+ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients' survival rate. Conditions including male sex, age >20 years, illness course [Symbol: see text]1 month, neutrophil count >0.1 × 10(9)/L, and reticulocyte count >10 × 10(9)/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.