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1.
Infection ; 40(6): 677-84, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22802096

RESUMO

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/etiologia , Infecções Respiratórias/etiologia , Adulto , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribavirina/uso terapêutico , Tomografia Computadorizada por Raios X , Transplante Homólogo
2.
Clin Infect Dis ; 51(6): 678-83, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20687839

RESUMO

BACKGROUND: Vancomycin-resistant enterococci (VRE) have triggered multiple outbreaks. However, VRE of genotype vanC appear not to be associated with outbreaks. The goal of this study was to estimate the risk of bloodstream infections in patients colonized with VRE of genotype vanC who received care from a bone marrow transplant unit for patients with leukemia, where only standard precautions were implemented for VRE of genotype vanC during the last 9 years. METHODS: Since 2000, all patients in the bone marrow transplant unit underwent routine VRE rectal screening, data were prospectively entered in a database, and isolates were molecularly characterized. Infection control policy required contact isolation for patients infected with VRE of genotype vanA or vanB but only standard precautions for patients infected with VRE of genotype vanC. RESULTS: From January 2000 to July 2008, 290 isolates of VRE of genotype vanC obtained from 273 different patients were identified, with an incidence of 25-43 isolates/year. Of 290 isolates, 285 (98%) were identified in rectal screening swabs, 5 were from other body sites, and none required specific treatment. During the entire study period, only 1 case of bloodstream infection was detected, reflecting an incidence of 1 (0.4%) of the 273 patients, or <0.2 cases per 1000 patient-days. No outbreaks were recorded. CONCLUSIONS: These data provide strong evidence that carriers of VRE of genotype vanC do not require contact isolation, thereby saving resources and potentially improving patient care. The genotype should be routinely determined in areas with a high prevalence of VRE of genotype vanC.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Isolamento de Pacientes , Resistência a Vancomicina , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Proteínas de Bactérias/genética , Transplante de Medula Óssea/efeitos adversos , Carbono-Oxigênio Ligases/genética , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Enterococcus/genética , Enterococcus/isolamento & purificação , Fezes/microbiologia , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Hospedeiro Imunocomprometido , Leucemia/complicações , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Peptídeo Sintases/genética , Fatores de Risco
3.
Am J Transplant ; 10(8): 1897-906, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20659095

RESUMO

To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984 and 2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/mortalidade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida
4.
Transpl Infect Dis ; 11(2): 100-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19175540

RESUMO

BACKGROUND: Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated. METHODS: We retrospectively identified influenza-infected patients with upper or lower respiratory tract infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice daily and serial nasal swabs were performed at the discretion of the treating physician. RESULTS: We identified 21 influenza infections in 19 patients: 19 with upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for PCR with a median influenza load of 5.9 log(10) copies/mL. Culture was positive in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and influenza B virus in 13 (62%) episodes. Two patients were sequentially infected by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%) patients were treated with oseltamivir for 11 days (median, interquartile range [IQR]: 8-14). No progression to lower RTI or mortality occurred. Shedding persisted for 12 days (median, IQR: 8-13). Absolute lymphocyte count at diagnosis correlated inversely with shedding of the virus (P<0.001). CONCLUSIONS: Oseltamivir is well tolerated and may reduce mortality of influenza virus-infected patients after HSCT. PCR may help to optimize diagnosis and to monitor treatment strategies.


Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Líquido da Lavagem Broncoalveolar/virologia , Feminino , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/virologia , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/virologia , RNA Viral/análise , Estudos Retrospectivos , Suíça , Fatores de Tempo , Resultado do Tratamento
5.
Dermatology ; 219(1): 32-41, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19407437

RESUMO

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in acute and chronic disease. Immune-mediated vessel attack and subsequent microvessel loss have been observed in skin of patients with chronic GVHD. OBJECTIVES: To test whether long-term survivors (LTS) after allogeneic HSCT without cutaneous GVHD show signs of persistent vascular remodeling. METHODS: Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a median follow-up of 17 years (range 11-26). Five were currently classified as having chronic GVHD other than skin involvement. RESULTS: LTS showed no significant difference in median microvessel density and relative vessel size distribution pattern compared to healthy controls. Past experience of GVHD and current status of chronic GVHD other than skin involvement had no impact on vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic type and patients with lichen sclerosus have significant microvessel loss in the upper dermis. CONCLUSION: The complex therapy of allogeneic HSCT had no sustained effect on the microvascular architecture of LTS when clinicopathological evidence of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic GVHD recovers completely after resolution of chronic cutaneous GVHD.


Assuntos
Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microvasos/patologia , Pele/irrigação sanguínea , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imuno-Histoquímica , Líquen Escleroso e Atrófico/patologia , Masculino , Microvasos/química , Pessoa de Meia-Idade , Esclerodermia Localizada/patologia , Dermatopatias/etiologia , Dermatopatias/patologia , Adulto Jovem , Fator de von Willebrand/análise
6.
Am J Transplant ; 8(10): 2149-57, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18828773

RESUMO

H-Y encoded gene products were the first to be recognized as clinically relevant minor histocompatibility antigens. Compared to other gender combinations, female donor/male recipient (FDMR) transplants are associated with increased graft-versus-host disease (GvHD), increased transplant-related mortality (TRM) and reduced risk of relapse. Still, their relative impact on transplant outcome remains controversial. We analyzed donor/recipient sex combination in 53,988 patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) between 1980 and 2005. We found a strong increase in chronic GvHD and late TRM and decreased survival in FDMR transplants irrespective of underlying disease. Conversely, FDMR patients had lower relapse rates. The negative effect on survival decreased with advancing disease stage as relapse protection became more important. Effects of H-Y alloreactivity were most pronounced in patients transplanted from HLA-matched donors and in those receiving transplants from an adult donor. Adjustment for acute and chronic GvHD only partially corrected the effects of H-Y alloreactivity. Analysis of the FDMR proportion over time indicated that the frequency of this gender combination has declined in unrelated transplants over the last 10 years. These data define the role of H-Y mismatching in allogeneic HSCT and support the current practice of avoiding female donors for male patients, if possible.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade/genética , Leucemia/terapia , Antígenos de Histocompatibilidade Menor/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/imunologia , Estudos Retrospectivos , Fatores Sexuais , Imunologia de Transplantes/genética
7.
Bone Marrow Transplant ; 42 Suppl 1: S7-S10, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18724308

RESUMO

Differences in the number of hematopoietic SCTs (HSCT), in transplant rates, in indications and in techniques between countries have been reported. They were attributed mainly to differences in the economic situation of the countries or to differences in prevalences of the disease. On the basis of the results of the annual activity survey on HSCT of the European Blood and Marrow Transplantation (EBMT), we have analyzed the factors associated with differences between more than 600 teams participating from more than 40 countries over a time span of 15 years. The results show a more complex situation. The gross national income per capita, number of transplant teams per 10 million inhabitants or per 10,000 km2, team size and team experience all impact on transplant activity. Furthermore, hitherto unknown factors must add to the decisions to perform or not to perform HSCT. These data illustrate that more research is needed to understand the mechanism of HSCT activity and to enable health-care agencies to provide the necessary infrastructure.


Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Europa (Continente) , Humanos , Sistema de Registros , Fatores de Tempo
8.
Bone Marrow Transplant ; 41(8): 687-705, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18084334

RESUMO

This report describes the hematopoietic stem cell transplantation (HSCT) activity in Europe in 2006 by indication, donor type and stem cell source. It illustrates differences compared to previous years and concentrates on the use of cord blood transplants. In 2006, there were 25 050 first HSCT, 9661 allogeneic (39%), 15 389 autologous (61%) and 3690 additional re- or multiple transplants reported from 605 centers in 43 participating countries. Main indications were leukemias (7963 (32%; 85% allogeneic)); lymphomas (14 169 (56%; 89% autologous)); solid tumors (1564 (6%; 95% autologous)); non-malignant disorders (1242 (5%; 90% allogeneic)) and non-classified 'others' (112 (1%)). There was an increase in allogeneic HSCT of 9% when compared to 2005, while autologous HSCT numbers remained similar. There were 544 allogeneic cord blood HSCT, which corresponds to 5% of all allogeneic HSCT. The majority, 67%, were used for patients with leukemia. The highest percentage of cord blood transplants, 27%, was seen for inherited disorders of metabolism. No autologous cord blood transplants were reported. The highest increase in allogeneic HSCT was observed for AML, which comprises 31% of all allogeneic HSCT. Numbers of autologous HSCT remained similar in most main indications. This data provide an update of the current HSCT experience in Europe.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Neoplasias/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Europa (Continente)/epidemiologia , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Neoplasias/epidemiologia , Transplante Autólogo/estatística & dados numéricos , Transplante Autólogo/tendências , Transplante Homólogo/estatística & dados numéricos , Transplante Homólogo/tendências
9.
Bone Marrow Transplant ; 42(7): 483-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18695668

RESUMO

Allogeneic hematopoietic SCT (HSCT) is increasingly considered an option in refractory or relapsing lymphoma. Today, most patients with B-cell lymphoma are treated with the monoclonal anti-CD20 antibody rituximab before HSCT. We hypothesized that prior therapy with rituximab might alter immune reconstitution after allogeneic transplantation due to in vivo depletion of B cells at the time of graft infusion. We studied B-cell immune reconstitution in 12 patients with lymphoma receiving rituximab 1-12 months before HSCT. Compared to an age- and sex-matched population of patients transplanted for myeloid malignancies, lymphoma patients with rituximab pretreatment showed significantly reduced B-cell counts at time of HSCT at +3, +6 and +12 months; B-cell counts reached values comparable to controls only 24 months after HSCT. In parallel, levels of immunoglobulins were markedly reduced for up to 2 years post transplant in patients with prior rituximab treatment. Two patients suffered from severe late bacterial infections to which the impaired humoral immunity may have contributed. In contrast, T- and NK-cell reconstitution was not different compared to control patients.In conclusion, B-cell reconstitution can be significantly delayed in allogeneic HSCT recipients with prior rituximab treatment. Rituximab appears to have clinical consequences beyond the immediate early post-transplant period.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma/imunologia , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Esquema de Medicação , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Linfoma/patologia , Linfoma/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Transplante Homólogo
10.
Bone Marrow Transplant ; 39(2): 71-87, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17213849

RESUMO

This EBMT activity report documents the haematopoietic stem cell transplantation (HSCT) activity in Europe in 2005. It provides numbers of HSCT by indication, donor type and stem cell source, lists the new practice of planned double transplants with allogeneic after autologous HSCT and concentrates on the increasing role of unrelated transplants over the last years. In 2005, there were 24,168 first HSCT, 8890 allogeneic (37%), 15,278 autologous (63%) and 3773 additional re- or multiple transplants reported from 597 centres in 43 participating countries. Main indications were leukaemias (7404 (31%; 82% allogeneic)); lymphomas (13,825 (57%; 89% autologous)); solid tumours (1655 (7%; 92% autologous)) and non-malignant disorders (1131 (5%; 93% allogeneic)). A total of 671 planned allogeneic after autologous HSCT were reported; the majority for myeloma (52%), lymphoma (28%) and acute myeloid leukaemia (11%). Compared to 2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT remained constant. The most noticeable increase was in unrelated HSCT, which comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed for leukaemias and in countries with high income according to World Bank criteria. These data illustrate the current experience in Europe and form the basis for patient counselling and decisions making at health care institutions.


Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Leucemia/terapia , Transtornos Linfoproliferativos/terapia , Neoplasias/terapia , Coleta de Dados , Europa (Continente)/epidemiologia , Humanos , Fatores de Tempo
11.
Bone Marrow Transplant ; 40(6): 515-22, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17646842

RESUMO

Identification of an unrelated HLA allele-matched hematopoietic stem cell (HSC) donor is a costly and time-consuming procedure. To improve search logistics, we have limited the search period to 6 months and have introduced a probability estimate of the chances of identifying a 10/10 HLA allele-matched donor. Probabilities were classified as high (>95%), intermediate (50%) and low (<5% chance) based on allele and haplotype frequencies. By analyzing 350 consecutive searches between 2002 and 2005 (1719 donors tested), the probability estimates turned out to be correct for 96% (high), 88% (low) and 56% (intermediate) patients. For searches with a high probability of success, at least one of the 10 most frequent haplotypes in Caucasoids was found in 69% of the patients, but in only 11% of the patients with a low-probability estimate (P<0.00001). Survival probability at 3 years was significantly higher for HSCT patients classified with a high-probability estimate when compared to patients in the intermediate/low-probability groups (74 vs 51 and 54% respectively, P=0.01). The same difference in survival probabilities was observed when only 10/10 matched unrelated HSCT patients were analyzed. In the intermediate-/low-probability groups, patients with alternative (haploidentical, autologous) or mismatched unrelated donors had similar survival estimates. Probability prediction is therefore feasible in the search process for unrelated donors and can guide the therapeutic strategy.


Assuntos
Algoritmos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Teste de Histocompatibilidade/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Alelos , Haplótipos , Humanos , Estimativa de Kaplan-Meier , Valor Preditivo dos Testes , Probabilidade , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos
12.
Bone Marrow Transplant ; 39(6): 335-40, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17342158

RESUMO

Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy. High-dose chemotherapy (HDC) for tumor debulking followed by reduced-intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) has been advocated as a concept. We previously treated 10 patients (group A) with BEAM chemotherapy followed by delayed RIC HSCT at day 28. We now report on the subsequent 11 patients receiving BEAM followed immediately by fludarabine/total body irradiation and allogeneic HSCT (group B), and compare the outcome to group A patients. Non-hematological toxicity before engraftment was comparable, only gut toxicity was higher in group B. Days in aplasia, days on antibiotics and length of hospital stay were significantly longer in group A. Cumulative incidence of acute (GvHD) >or=grade II and incidence of chronic GvHD were lower in group B. At last follow-up, seven patients in group A were alive, with six of them in complete remission. In group B, nine patients were alive, seven of them in complete remission. No significant difference in estimated 3-year overall survival was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. Allogeneic HSCT with standard BEAM conditioning is a valid alternative for patients with resistant/relapsed lymphoma, which might be considered earlier in the disease course.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Tumor , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Indução de Remissão/métodos , Transplante Homólogo
13.
Clin Microbiol Infect ; 13(8): 751-3, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17610597

RESUMO

Visceral leishmaniasis is rare in western Europe, but may be life-threatening in immunocompromised patients. It is therefore important to understand the incidence of the disease in a non-endemic area and its relationship with immunosuppressive conditions. Between 1990 and 2005, 12 patients were diagnosed with leishmaniasis at Basel University Hospital, Switzerland. Eleven presented with visceral symptoms and ten had an underlying immunosuppressive condition. Since increasing numbers of immunosuppressed patients have a history of travel to endemic countries, an association of visceral leishmaniasis with cellular immunosuppression (other than that associated with human immunodeficiency virus) might become more frequent in non-endemic areas.


Assuntos
Hospedeiro Imunocomprometido , Leishmania donovani/patogenicidade , Leishmaniose Visceral/imunologia , Adulto , Idoso , Animais , Emigração e Imigração , Feminino , Humanos , Leishmania donovani/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suíça , Viagem
14.
Leukemia ; 20(2): 247-53, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16408102

RESUMO

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.


Assuntos
Linfoma de Burkitt/genética , Análise Citogenética/métodos , Leucemia Mieloide/genética , Leucemia-Linfoma de Células T do Adulto/genética , Técnicas de Diagnóstico Molecular/métodos , Síndromes Mielodisplásicas/genética , Segunda Neoplasia Primária/genética , Doença Aguda , Adulto , Linfoma de Burkitt/classificação , Linfoma de Burkitt/diagnóstico , Criança , Aberrações Cromossômicas , Estudos de Coortes , Feminino , Humanos , Cariotipagem , Leucemia Mieloide/classificação , Leucemia Mieloide/diagnóstico , Leucemia-Linfoma de Células T do Adulto/classificação , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Masculino , Síndromes Mielodisplásicas/complicações , Segunda Neoplasia Primária/classificação , Segunda Neoplasia Primária/diagnóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Medição de Risco , Organização Mundial da Saúde
15.
Leukemia ; 20(3): 477-84, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16453005

RESUMO

We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at the time of allogeneic hematopoietic stem cell transplantation (HSCT) on transplant-related mortality (TRM), relapse rate and survival probability after HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher in patients, who achieved any CyR prior to HSCT than in patients without CyR (63.6 vs 49.2%: P = 0.019). Survival probabilities in patients, who achieved a major CyR were better than in patients with minimal and minor CyR or in patients with no CyR (69.4 vs 58.8% vs 49.2%: P = 0.040). TRM and survival of chronic phase patients without CyR at the time of HSCT were similar to that of patients transplanted in advanced phase. Both groups combined had an outcome inferior to patients with at least minimal CyR (TRM, Gray test: P = 0.016, survival, log-rank test: P = 0.002). Univariate and multivariate analyses identified CyR prior to or at HSCT as a strong and independently favorable prognostic factor. We therefore conclude that allogeneic HSCT in CyR should be investigated prospectively as an alternative treatment option in defined patient groups.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Prognóstico , Recidiva , Análise de Sobrevida , Transplante Homólogo
16.
Leukemia ; 31(8): 1752-1759, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28270691

RESUMO

Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/imunologia , Teste de Histocompatibilidade , Humanos , Estudos Retrospectivos , Transplante Homólogo
17.
Bone Marrow Transplant ; 52(3): 357-362, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27892949

RESUMO

In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and the European Society for Blood and Marrow Transplantation)-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty-eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies, 61% as interesting information. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. This survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic haematopoietic stem cell transplantation applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Fidelidade a Diretrizes , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
18.
Bone Marrow Transplant ; 52(5): 671-677, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28112744

RESUMO

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Atenção à Saúde/estatística & dados numéricos , Atenção à Saúde/tendências , Previsões , Saúde Global/estatística & dados numéricos , Saúde Global/tendências , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , América Latina , Fatores Socioeconômicos , Inquéritos e Questionários
19.
Leukemia ; 31(11): 2398-2406, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28804124

RESUMO

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Análise de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Bone Marrow Transplant ; 37(12): 1069-85, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16757972

RESUMO

This fifteenth annual European Group for Blood and Marrow Transplantation activity report lists the transplant activity in Europe in 2004 and documents the changes in indication over the past 15 years. In 2004, there were 22 216 first hematopoetic stem cells (HSCT), 7407 allogeneic (33%), 14 809 autologous (67%) and 4378 additional re- or multiple transplants reported from 592 centres in 38 European and five affiliated countries. Main indications were leukemias (7045 (32%; 78% allogeneic)); lymphomas (12 310 (55%; 94% autologous)); solid tumors (1759 (8%; 93% autologous)) and nonmalignant disorders (1015 (5%; 92% allogeneic)). In comparison, 145 teams from 20 countries performed 4234 HSCT (2137 allogeneic, 50%; 2097 autologous, 50%) in 1990. The overall increase was accompanied by major changes. Stem cell source changed from bone marrow to peripheral blood. More than one-third of allogeneic HSCT are now from unrelated donors. Reduced intensity conditioning is employed for one-third of allogeneic HSCT. Leukemias for allogeneic and lymphoproliferative disorders for autologous HSCT continue to increase. The decline in HSCT for chronic myeloid leukemia appears to level off for the first time since 1999. These data are informative for patient counselling and decision making for health care professionals.


Assuntos
Pesquisas sobre Atenção à Saúde , Transplante de Células-Tronco Hematopoéticas , Neoplasias/terapia , Doadores de Tecidos , Condicionamento Pré-Transplante , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas/história , História do Século XX , História do Século XXI , Humanos , Masculino , Neoplasias/história , Estudos Retrospectivos , Condicionamento Pré-Transplante/história , Transplante Autólogo , Transplante Homólogo
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