RESUMO
Risk factors associated with the development of aGVHD in the gastrointestinal tract have not been studied in depth. We retrospectively assessed 25 pediatric patients with MDS and JMML and compared the treatment outcome of two different conditioning regimens. Seventeen children (68%) underwent conditioning with busulfan (Bu), cyclophosphamide (Cy), and melphalan (Mel) and eight children (32%) with Bu and Cy. Gastrointestinal aGVHD stages II-IV (day 0-100) were observed in 47% (eight of 17) of the patients in the BuCyMel group and in none (0 of 8) in the BuCy group (p < 0.05). In patients who developed gastrointestinal aGVHD stages III-IV, a 24-h variation in the Bu concentration with a nighttime peak was noted. HC and liver aGVHD stages II-IV were observed in 47% (eight of 17) and 35% (six of 17) after BuCyMel conditioning and in 0% (0 of 17) and 12.5% (one of eight) after BuCy conditioning. The overall survival rate was 53% (nine of 17) in the BuCyMel group and 62.5% (five of eight) in the BuCy group. In conclusion, the addition of melphalan to the BuCy conditioning regimen resulted in severe gastrointestinal complications and did not improve overall survival.
Assuntos
Bussulfano/efeitos adversos , Ciclofosfamida/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Melfalan/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Leucemia Mielomonocítica Aguda/terapia , Masculino , Melfalan/administração & dosagem , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
Neurological complications, often due to viral reactivation, after allogeneic hematopoetic stem cell transplantation (HSCT) are associated with increased mortality. Here, cerebrospinal fluid from 20 HSCT patients with neurological symptoms were analyzed and found to be negative by PCR for BK virus, JC virus, KI, WU and Merkel cell polyomavirus DNA.
Assuntos
Vírus BK/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus JC/isolamento & purificação , Células de Merkel/virologia , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/complicações , Polyomavirus/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/virologia , Adulto JovemRESUMO
The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P=0.001), MC (OR 6.0; 95% CI 2.1-17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.
Assuntos
Cistite/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus , Adolescente , Adulto , Idoso , Vírus BK/patogenicidade , Criança , Pré-Escolar , Cistite/fisiopatologia , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Infecções por Polyomavirus/fisiopatologia , Infecções por Polyomavirus/urina , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/métodos , Infecções Tumorais por Vírus/fisiopatologia , Infecções Tumorais por Vírus/urinaRESUMO
BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC.
Assuntos
Vírus BK/fisiologia , Cistite/etiologia , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Urina/virologia , Adulto , Criança , Doença Enxerto-Hospedeiro/virologia , Humanos , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/virologia , Carga ViralRESUMO
To investigate if children who later developed acute lymphoblastic leukaemia (ALL) were prenatally infected with HHV-6 and/or EBV, Guthrie cards taken at birth were analysed by PCR. Guthrie cards from 54 patients with ALL and 47 healthy controls matched for age and birth place were tested negative for both HHV-6 and EBV DNA. All samples contained amplifiable DNA when tested by HLA-DQ PCR. Our negative findings suggest that childhood ALL is unlikely to be associated with an in utero infection with EBV or HHV-6.
Assuntos
DNA Viral/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 6/isolamento & purificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Adolescente , Animais , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Humanos , Lactente , Reação em Cadeia da Polimerase , Infecções por Roseolovirus/complicações , Infecções Tumorais por Vírus/complicaçõesRESUMO
BACKGROUND: Haemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with reactivation of BK virus (BKV) manifested as BK viruria. However, it has been suggested that BKV reactivation alone is not responsible for HC, since BKV can be detected in the urine of 50-90% of all adult BMT patients. OBJECTIVES: In the present study, we analysed if BK viruses with specific mutations in the non-coding control region (NCCR) or in the region encoding the major capsid protein (VP1) were more frequently associated to the appearance of HC in BMT patients. STUDY DESIGN: The NCCR and the region encoding VP1 of BKV excreted in the urine from 25 BMT patients, 16 with and nine without HC, were sequenced by an ABI Prism Big Dye terminator cycle sequencing ready reaction kit. RESULTS AND CONCLUSIONS: A statistically significant (P=0.019) overrepresentation of C to G mutations within the NCCR Sp1 binding site was observed in 7/16 (43%) patients with HC (six cases at position 249 (P=0.035) and one case at position 251), as compared with 0/9 (0%) of the patients without HC. Major differences were not observed in the VP1 sequences of patients with and without HC. BKV WW and WWT-variants as well as BKV subtype I were most commonly encountered in both groups of patients. In conclusion, C to G point mutations, within the BKV NCCR Sp1 binding site, were significantly more common in patients with HC, suggesting that these mutations may be indicative for the clinical diagnosis of HC and could influence the virulence of the virus.
Assuntos
Vírus BK/genética , Transplante de Medula Óssea/efeitos adversos , Cistite/virologia , DNA Viral/genética , Infecções por Papillomavirus/virologia , Fator de Transcrição Sp1/genética , Infecções Tumorais por Vírus/virologia , Sítios de Ligação , Capsídeo/genética , Cistite/complicações , Cistite/urina , DNA Viral/metabolismo , Genes Virais , Hematúria/complicações , Hemorragia/complicações , Hemorragia/terapia , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/urina , Mutação Puntual , Fator de Transcrição Sp1/metabolismo , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/urinaRESUMO
Polyomaviruria was observed in one-third of all renal transplant patients, irrespective of whether their renal grafts came from a living or cadaver donor, and was not correlated to graft rejection episodes. This suggests that the renal graft ischemia period is not the major cause of polyomavirus reactivation and that reactivation of polyomavirus is not a dominant cause of graft rejection.
Assuntos
Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/urina , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Rejeição de Enxerto , Humanos , Hipotermia Induzida , Isquemia , Pessoa de Meia-Idade , Fatores de TempoRESUMO
JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML.
Assuntos
DNA Viral/líquido cefalorraquidiano , Encefalite Viral/virologia , Infecções por Enterovirus/virologia , Herpes Simples/virologia , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/virologia , Meningite Viral/virologia , Esclerose Múltipla/virologia , Adulto , Encefalite Viral/líquido cefalorraquidiano , Infecções por Enterovirus/líquido cefalorraquidiano , Herpes Simples/líquido cefalorraquidiano , Humanos , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidianoRESUMO
In allogeneic bone marrow transplanted (BMT) patients BK virus (BKV) reactivation has been associated with haemorrhagic cystitis (HC). However, it is far from obvious which patients will develop HC, since BKV, a human polyomavirus, is ubiquitious and infects children at an early age. To investigate if a primary BKV infection, as such or possibly due to transmission of BKV by the marrow graft during BMT, was correlated to the development of HC, 45 children were followed for possible BKV seroconversion and development of HC at different time points after BMT. Serum samples were collected from the 45 allogeneic BMT children and their donors before transplantation, and from the patients at 3, 6 and 12 months after BMT. These sera were analysed for the presence of specific antibodies towards BKV by hemagglutination inhibition (HAI) and by IgG- and IgM-class specific enzyme linked immunosorbent (ELISA) assays. Twelve of the 45 BMT children had a documented episode of HC or hematuria. All patients and 98% of the donors were HAI positive before BMT, while with ELISA 87% of the patients and 84% of the donors were positive. Moreover, most HC and hematuria children (11/12) were seropositive with both assays before BMT, making it impossible to investigate possible BKV transmission through the bone marrow graft during BMT by serology. Still, serological changes such as ELISA seroconversion, IgM antibodies and/or HAI titer increases were significantly (p=0.016) more common in patients with HC (58%) than without HC (24%), but these changes occured mainly after HC symptomatology had already resolved. However, there was a near significant difference (p=0.053) in BKV seroprevalence by ELISA among the donors of patients with HC or hematuria (67%) as compared to the donors (91%) of patients without HC.