RESUMO
This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications.
Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Hepatite C/tratamento farmacológico , Hepatite C/fisiopatologia , Adolescente , Adulto , Antivirais/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Doenças Hematológicas/cirurgia , Doenças Hematológicas/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Sobreviventes , Resultado do Tratamento , Adulto JovemRESUMO
We have previously shown that hemopoietic stem cell transplant (HSCT) recipients can be stratified on day+7 as having low, intermediate or a high risk of transplant-related mortality (TRM). With the aim of reducing TRM and GVHD, intermediate and high-risk patients (n=170) were randomized to receive anti-thymocyte globulin (ATG, thymoglobuline) on day+7 (n=84) or no treatment (n=86) (controls). There was a reduction of TRM from 35% in controls to 29% in ATG patients (P=0.3), of acute GVHD III-IV from 15 to 5% (P=0.02) and of chronic GVHD from 26 to 11% (P=0.03); survival was comparable. The predictive value of the day+7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high risk, respectively, P=0.03), whereas ATG abrogated this predictive effect (29 vs 29%). ATG reduced GVHD (P=0.006) in high-risk patients, but not in patients with an intermediate risk. In conclusion, we confirm that TRM can be predicted on the basis of day+7 laboratory values, after alternative donor HSCT; in high-, but not intermediate-risk patients, the administration of ATG on day+7 reduces GVHD. These results may represent a platform for risk-adapted post transplant immune modulation.
Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adulto , Animais , Causas de Morte , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Análise Multivariada , Coelhos , Recidiva , RiscoRESUMO
Graft rejection, with persistent pancytopenia, is well documented after allogeneic BMT (hematopoietic SCT (HSCT)) for severe aplastic anemia (SAA) and the prognosis is poor. The recovery of host-hematopoiesis, autologous recovery (AR), after allogeneic HSCT is a rare event and the incidence and long-term survival are unknown. We report a retrospective analysis of consecutive patients in the Aplastic Anaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT-WPSAA) registry between 1973 and 2005. A total of 45 cases of AR, of 1205 patients transplanted for SAA in 57 centers are reported. We describe characteristics and long-term outcome of patients with AR, compared with SAA patients from participating transplant centers without AR (n=1024) and patients with graft rejection (n=136) without autologous recovery. The estimated cumulative incidence of AR was 4.2% (3.1-5.6) (confidence interval (CI) 95%) with an OS of 84% (95% CI 83-107%). The OS of the control group was 74% (81-90) at 10 years of follow up, whereas the patients with graft failure had an OS of 16% (CI 12-28%). This retrospective analysis establishes the incidence and long-term survival of patients experiencing AR after allogeneic HSCT for SAA.
Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adolescente , Adulto , Anemia Aplástica/epidemiologia , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto , Doença Enxerto-Hospedeiro , Hematopoese , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Lactente , Masculino , Pancitopenia , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Sobreviventes/estatística & dados numéricos , Adulto JovemRESUMO
The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12-82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL.
Assuntos
Linfoma/terapia , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Feminino , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Células-Tronco/citologia , Células-Tronco/metabolismo , Fatores de Tempo , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.
Assuntos
Antifúngicos/administração & dosagem , Equinocandinas/administração & dosagem , Pneumopatias Fúngicas/prevenção & controle , Transplante de Células-Tronco , Adulto , Caspofungina , Intervalo Livre de Doença , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Humanos , Lipopeptídeos , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Fanconi anemia (FA) is an autosomal recessive disease characterized by pancitopenia, congenital malformations, predisposition to cancers and chromosomal instability. We report the clinical and molecular features of a patient initially identified as a potential FA case only because of chemotherapy toxicity during the treatment of a T-lineage acute lymphoblastic leukemia (ALL). Cells from this patient showed a moderate chromosomal instability, increasing sensitivity to DNA crosslinking agents but normal response to ionizing radiation. The analysis of FA proteins demonstrated a marked reduction of FANCD2 (>95%), but normal levels of FANCA or FANCG. Interestingly, this defect was associated with a homozygous missense mutation of FANCD2, resulting in a novel amino-acid substitution (Leu153Ser) at residue Leu153, which is highly conserved through evolution. The FANCD2(L153S) protein, whose reduced expression was not due to impaired transcription, was detected also in its monoubiquitinated form in the nucleus, suggesting that the mutation does not affect post-translation modifications or subcellular localization but rather the stability of FANCD2. Therefore, the hypomorphic Leu153Ser mutation represents the first example of a FANCD2 defect that might promote clonal progression of tumors, such as T-ALL, and severe chemotherapy toxicity in patients without any clinical manifestations typical of FA.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Mutação , Substituição de Aminoácidos , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antígenos CD13 , Criança , Instabilidade Cromossômica , Progressão da Doença , Anemia de Fanconi/genética , Humanos , Infecções/etiologia , Infecções/genética , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Masculino , Pancitopenia/induzido quimicamente , Pancitopenia/genética , Indução de Remissão , Lectina 3 Semelhante a Ig de Ligação ao Ácido SiálicoRESUMO
We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a significant survival advantage (P = 0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/fisiologia , Ciclosporina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/fisiologia , Metotrexato/uso terapêutico , Irmãos , Quimeras de Transplante , Adolescente , Adulto , Criança , Feminino , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante HomólogoRESUMO
Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.
Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Irmãos , Doadores de Tecidos , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Humanos , Lactente , Assistência de Longa Duração/métodos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Fluorescence in situ hybridization and comparative genomic hybridization characterized 6p rearrangements in eight primary and in 10 secondary myeloid disorders (including one patient with Fanconi anemia) and found different molecular lesions in each group. In primary disorders, 6p abnormalities, isolated in six patients, were highly heterogeneous with different breakpoints along the 6p arm. Reciprocal translocations were found in seven. In the 10 patients with secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS), the short arm of chromosome 6 was involved in unbalanced translocations in 7. The other three patients showed full or partial trisomy of the 6p arm, that is, i(6)(p10) (one patient) and dup(6)(p) (two patients). In 5/7 patients with unbalanced translocations, DNA sequences were overrepresented at band 6p21 as either cryptic duplications (three patients) or cryptic low-copy gains (two patients). In the eight patients with cytogenetic or cryptic 6p gains, we identified a common overrepresented region extending for 5-6 megabases from the TNF gene to the ETV-7 gene. 6p abnormalities were isolated karyotype changes in four patients. Consequently, in secondary AML/MDS, we hypothesize that 6p gains are major pathogenetic events arising from acquired and/or congenital genomic instability.
Assuntos
Cromossomos Humanos Par 6/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Segunda Neoplasia Primária/genética , Translocação Genética/genética , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Sensibilidade e EspecificidadeRESUMO
We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (Assuntos
Anemia Aplástica/terapia
, Soro Antilinfocitário/administração & dosagem
, Ciclofosfamida/administração & dosagem
, Doadores de Tecidos
, Condicionamento Pré-Transplante/métodos
, Vidarabina/análogos & derivados
, Adolescente
, Adulto
, Anemia Aplástica/complicações
, Anemia Aplástica/mortalidade
, Causas de Morte
, Criança
, Pré-Escolar
, Quimioterapia Combinada
, Rejeição de Enxerto
, Doença Enxerto-Hospedeiro/prevenção & controle
, Transplante de Células-Tronco Hematopoéticas/efeitos adversos
, Transplante de Células-Tronco Hematopoéticas/métodos
, Transplante de Células-Tronco Hematopoéticas/mortalidade
, Humanos
, Análise de Sobrevida
, Vidarabina/administração & dosagem
RESUMO
PURPOSE: Older age and a previously failed autologous stem-cell transplantation (SCT) are poor prognostic factors for patients receiving myeloablative conditioning and allogeneic SCT. Reduced-intensity conditioning (RIC) regimens achieved a significant reduction of treatment-related mortality, but the influence of previously described risk factors on the outcome of this novel transplantation strategy have not been fully analyzed yet. PATIENTS AND METHODS: One hundred fifty patients with advanced hematologic malignancies received a RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/m2), and cyclophosphamide (60 mg/kg), followed by an allogeneic transplantation from an HLA-identical sibling donor. Patients were divided into two cohorts according to age; 90 patients were younger than 55 years, and 60 patients were 55 years old or older. The other pretransplantation characteristics were fairly balanced. RESULTS: Actuarial 5-year nonrelapse mortality (NRM) rate was not statistically different between the groups (13% in the younger group and 19% in the older group). By univariate and multivariate analysis, NRM was significantly higher in older patients who previously experienced failure with an autograft. The occurrence of grade 3 to 4 acute graft-versus-host disease (GVHD) or extensive chronic GVHD was associated with a higher NRM in both age cohorts. Overall survival (OS) was not statistically different between the younger (66%) and older groups (61%). By multivariate analysis, refractory disease was associated with a worse OS irrespective of age group. CONCLUSION: RIC transplantations show a rather low NRM, and age > or = 55 years per se cannot be considered a risk factor anymore. The timing of transplantation and novel strategies for the prevention of severe GVHD could further improve patient outcome.
Assuntos
Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Idoso , Análise de Variância , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/mortalidade , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Medição de Risco , Análise de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.
Assuntos
Anemia Aplástica/genética , Antígenos de Diferenciação/genética , Éxons/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adolescente , Adulto , Antígenos CD , Antígeno CTLA-4 , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População BrancaRESUMO
Over the last 25 years, the numbers of hematopoietic stem cell transplant (SCT) patients have increased rapidly. Infections have been major obstacles for successful transplantation. Thus, infection prevention is very important in transplant recipients. As the results of transplantation have improved, the number of long-term survivors has increased. Vaccination is a potentially important strategy for reducing the risk for vaccine-preventable infections after SCT. The EBMT produced recommendations for vaccination of SCT recipients published in Bone Marrow Transplantation in 1995. This paper updates the previous recommendations based on current knowledge.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Infecções Oportunistas/prevenção & controle , Vacinação/normas , Ensaios Clínicos como Assunto , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis , Europa (Continente) , Diretrizes para o Planejamento em Saúde , Humanos , Esquemas de Imunização , Controle de Infecções/métodos , RiscoRESUMO
Hepatitis B virus/hepatitis C virus (HBV/HCV) positive patients undergoing haemopoietic stem cell transplantation (HSCT) are at risk of hepatitis reactivation and fatal liver failure: we have conducted a retrospective study to assess the risk in 20 Italian transplant centres. A total of 90 patients infected with HBV (n=33) or HCV (n=57) receiving allogeneic (n=36) or autologous (n=54) haemotopoietic stem cell transplant (HSCT) between 1996 and 2000 were reviewed. The biochemical profiles and outcomes of infection-related liver disease were also analysed. The risk of death at 2 years was comparable when considering type of infection (3% for HBV vs 8% for HCV, P=0.6) or type of HSCT (7% for allogeneic vs 5% for autologous HHSCT, P=0.34). Hepatitis reactivation followed by resolution was more frequent in HCV+ than in HBV+ patients receiving an allograft (100% vs 16%, P=0.004). In HBV+ cases, risk of reactivation was comparable after autologous or allogeneic transplantation (66 vs 81%, P=0.3), but liver disease was more severe and occurred earlier in the autologous group. Our results indicate that HBV and HCV infection should not be taken as an absolute contraindication for HSCT and the risk of life-threatening liver complications are similar after allogeneic or autologous transplants.
Assuntos
Hepacivirus/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite B/terapia , Hepatite C/terapia , Falência Hepática/epidemiologia , Transplante de Células-Tronco/efeitos adversos , Adulto , Feminino , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/epidemiologia , Humanos , Falência Hepática/virologia , Testes de Função Hepática , Masculino , Seleção de Pacientes , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo , Ativação ViralRESUMO
Allogeneic blood or bone marrow transplantation is a successful treatment for leukaemia and severe aplastic anaemia (SAA). Graft rejection following transplantation for leukaemia is a rare event but leukaemic relapse may occur at varying rates, depending upon the stage of leukaemia at which the transplant was undertaken and the type of leukaemia. Relapse is generally assumed to occur in residual host cells, which are refractory to, or escape from the myeloablative conditioning therapy. Rare cases have been described, however, in which the leukaemia recurs in cells of donor origin. Lack of a successful outcome of blood or bone marrow transplantation for severe aplastic anaemia (SAA), however, is due to late graft rejection or graft-versus-host disease. Leukaemia in cells of donor origin has rarely been reported in patients following allogeneic bone marrow transplantation for SAA. This report describes leukaemic transformation in donor cells following a second allogeneic BMT for severe aplastic anaemia. PCR of short tandem repeats in bone marrow aspirates and in colonies derived from BFUE and CFU-GM indicated the donor origin of leukaemia. Donor leukaemia is a rare event following transplantation for severe aplastic anaemia but may represent the persistence or perturbation of a stromal defect in these patients inducing leukaemic change in donor haemopoietic stem cells.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/efeitos adversos , Transformação Celular Neoplásica , Leucemia/etiologia , Anemia Aplástica/complicações , Criança , Feminino , Humanos , Leucemia/patologia , Reação em Cadeia da Polimerase , Sequências de Repetição em Tandem/genética , Doadores de Tecidos , Quimeras de Transplante , Transplante HomólogoRESUMO
Granulocyte-colony stimulating factor (G-CSF) is being increasingly used in healthy volunteers to harvest haemopoietic stem cells. A possible role of G-CSF in the development of clonal disorders or leukaemia has been suggested. We analysed 144 patients with aplastic anaemia treated with immunosuppression protocols with or without G-CSF, with normal cytogenetics at diagnosis or immediately after immunosuppression. Our findings indicated that the risk of developing myelodysplasia or leukaemia was similar in patients with aplastic anaemia on immunosuppressive treatment with or without G-CSF. Therefore, it seems unlikely that G-CSF causes leukaemia in healthy volunteers.
Assuntos
Anemia Aplástica/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/induzido quimicamente , Adolescente , Adulto , Idoso , Soro Antilinfocitário/efeitos adversos , Soro Antilinfocitário/uso terapêutico , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Hemoglobinúria Paroxística/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Lactente , Leucemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Adolescente , Adulto , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out.
Assuntos
Transplante de Medula Óssea , Doenças Hematológicas/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Lactente , Masculino , Fatores de TempoRESUMO
We have analyzed 2,002 patients grafted in Europe between 1976 and 1998 from an identical twin (n = 34), from an HLA-identical sibling (n = 1,699) or from an alternative donor (n = 269), which included unrelated and family mismatched donors. The proportions of patients surviving in these three groups are, respectively, 91, 66 and 37%: major causes of failure were acute graft-versus host disease (GvHD) (11%), infection (12%), pneumonitis (4%), rejection (4%). In multivariate Cox analysis, factors predicting outcome were patient's age (p < 0.0001), donor type (p < 0.0001), interval between diagnosis and bone marrow transplantation (BMT) (p < 0.0005), year of BMT (p = 0.0005) and female donor for a male recipient (p = 0.02). Patients were then divided in two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24% (p < 0.00001). Improvements were seen mostly for grafts from identical siblings (from 54 to 75%, p < 0.0001), and less so for alternative-donor grafts (from 28 to 35%; p = 0.07). Major changes have occurred in the BMT protocol: decreasing use of radiotherapy in the conditioning regimen (from 35 to 24%; p < 0.0001) and increasing use of cyclosporin (with or without methotrexate) for GvHD prophylaxis (from 70 to 98%; p < 0.0001). In conclusion, the outcome of allogeneic BMT for patients with severe aplastic anemia has considerably improved over the past two decades: young patients, grafted early after diagnosis from an identical sibling, have currently an over 80% chance of long-term survival. Transplants from twins are very successful as well. The risk of complications with alternative donor transplants is still high.