RESUMO
PURPOSE: BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation. METHODS: We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period. RESULTS: The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor. CONCLUSIONS: Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.
Assuntos
Vírus BK , Cistite , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Estomatite/virologia , Infecções Tumorais por Vírus , Adulto , Idoso , Cistite/mortalidade , Cistite/virologia , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/mortalidade , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Infecções Tumorais por Vírus/mortalidade , Infecções Tumorais por Vírus/virologia , Infecções Urinárias , Urina/virologia , Adulto JovemRESUMO
Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available in urgent clinical situations, we developed a rapid protocol for their isolation by overnight stimulation of donor blood cells with peptides derived from 11 EBV antigens, interferon-gamma surface capture, and immunomagnetic separation. Six patients with PTLD received 1 transfusion of EBV-specific T cells. No response was seen in 3 patients who had late-stage disease with multiorgan dysfunction at the time of T-cell transfer. In 3 patients who received T cells at an earlier stage of disease, we observed complete and stable remission of PTLD. Two patients have remained free from EBV-associated disease for more than 2 years. CD8(+) T cells specific for EBV early antigens rapidly expanded after T-cell transfer, temporarily constituted greater than 20% of all peripheral blood lymphocytes, and were maintained throughout the observation period. Thus, a rapid and sustained reconstitution of a protective EBV-specific T-cell memory occurred after the infusion of small numbers of directly isolated EBV-specific T cells.
Assuntos
Antígenos Virais/farmacologia , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Transfusão de Linfócitos , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Peptídeos/farmacologia , Linfócitos T/transplante , Proteínas Virais/farmacologia , Adulto , Anemia Aplástica/imunologia , Anemia Aplástica/terapia , Anemia Aplástica/virologia , Antígenos Virais/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Humanos , Memória Imunológica , Interferon gama , Leucaférese/métodos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virologia , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Indução de Remissão , Transplante de Células-Tronco , Linfócitos T/imunologia , Transplante Homólogo , Proteínas Virais/imunologiaRESUMO
Cytomegalovirus (CMV) positive recipients of CMV negative bone marrow bear a significantly higher risk of developing CMV disease compared to all other constellations. Here, we report a case of severe CMV induced esophagitis after allogeneic bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. The patient developed the first symptoms between day 10 and 20 after dose reduced conditioning and HLA-matched unrelated stem cell transplantation. Esophageal tissue biopsies as well as peripheral blood proved positive for CMV DNA by PCR. Treatment with acyclovir, ganciclovir, foscarnet, cidofovir, and immunoglobulines resulted in elimination of CMV in peripheral blood but not in clinical improvement. Only tapering of cyclosporine at day +120 eventually led to the development of CMV-specific T-cells and resolution of esophagitis.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Esofagite/etiologia , Imunossupressores/efeitos adversos , Condicionamento Pré-Transplante/métodos , Antivirais/uso terapêutico , Quimioterapia Combinada , Esofagite/tratamento farmacológico , Feminino , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/terapia , Humanos , Pessoa de Meia-Idade , Linfócitos T/imunologia , Transplante HomólogoRESUMO
We tested blood samples of 25 pediatric renal transplant recipients for Epstein-Barr virus (EBV) DNA load by quantitative polymerase chain reaction (PCR). Eleven of these transplant recipients showed clinical persistent mononucleosis-like symptoms years after transplantation (Tx). A quantitation of EBV DNA by PCR in peripheral blood lymphocyte (PBL) and serum samples revealed variable EBV DNA titers. The majority of EBV PCR results in samples of the 14 asymptomatic transplant recipients was repeatedly below detection limit. In contrast, patients with mononucleosis-like symptoms showed persistent EBV genome titers over a period of 6 months, ranging from 75 to 18 750 copies/10 000 PBL and from 680 to 335 000 copies/mL serum, respectively. One child suffering from this mononucleosis-like condition developed an EBV-associated Burkitt-like lymphoma 29 months after Tx. Whereas clinical and histological investigations did not indicate a post-transplant lymphoproliferative disorder (PTLD) until tumor detection, EBV titers in PBL and serum had been high for at least 8 months. We propose that pediatric transplant recipients who show both, recurrent mononucleosis-like symptoms and a sustained high EBV genome load, are at increased risk for severe EBV-related post-transplant complications.