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Biomedical subjects

Holger Hebart

Publications and source records attributed to Holger Hebart.

At least 19 recordsLinked to original sources
PubMed2006

Management of sepsis in neutropenia: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

These guidelines from the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO) give recommendations for the management of adults with neutropenia and the diagnosis of sepsis. The guidelines are written for clinicians and focus on pathophysiology, diagnosis, and treatment of sepsis. The manuscript contains evidence-based recommendations for the assessment of the quality and strength of the data.

Cardiotonic Agents↗
PubMed2006

Polymorphisms in the genes encoding chemokine receptor 5, interleukin-10, and monocyte chemoattractant protein 1 contribute to cytomegalovirus reactivation and disease after allogeneic stem cell transplantation.

We analyzed 90 polymorphisms in 17 genes related to immune function for association with human cytomegalovirus (HCMV) reactivation and disease in patients after allogeneic stem cell transplantation. We found relevant markers (i) in CCR5 and IL-10 genes conferring a higher risk for the development of HCMV disease and (ii) in the MCP1 gene associated with HCMV reactivation. Testing of high-risk patients for the presence of these single-nucleotide polymorphisms might be useful for individualizing antiviral prophylaxis.

Adolescent↗
PubMed2005

Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation.

Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (SCT). Valganciclovir (V-GCV) is an oral prodrug hydrolyzed to the anti-CMV drug ganciclovir (GCV). A randomized, multicenter, crossover, open-label clinical trial compared exposure to GCV after V-GCV and intravenous GCV (IV-GCV) as preemptive therapy for CMV disease in SCT. The primary objective was to compare exposure to GCV in patients with CMV infection stratified for intestinal graft-versus-host disease (I-GVHD). Secondary objectives were the assessment of safety and efficacy. Patients without I-GVHD had a higher exposure to GCV after V-GCV when compared with IV-GCV (area under the concentration-time curve from drug administration to last observed concentration after 12 hours [AUC(0-12)] 53.8 +/- 17.97 microg/mL . h [mean +/- SD] vs 39.5 +/- 13.91; P < .001; ratio of V-GCV/IV-GCV was 1.4; 90% confidence interval [CI], 1.2-1.5). This was also true in patients with I-GVHD grades I-II (AUC(0-12) 52.9 +/- 21.75 vs 33.1 +/- 12.97 mug/mL . h; P = .018; ratio 1.6; 90% CI, 1.3-2.0). Absolute bioavailability of GCV after V-GCV was approximately 75% in individuals with or without I-GVHD grades I-II. No severe GCV-related toxicity was observed and efficacy and safety was comparable (84-day follow-up). This supports the use of V-GCV in SCT, even in patients with I-GVHD grades I-II. Due to higher exposure after V-GCV compared with IV-GCV, patients should be monitored carefully for safety reasons.

Administration, Oral↗
PubMed2005

Meeting report: primary central nervous system lymphoma: standards of care and future perspectives.

A standard of care for patients with primary central nervous system lymphoma (PCNSL) has not been defined. Current controversies concern, amongst others, the role, dose and timing of radiotherapy, the role of intrathecal chemotherapy and the delineation of age-specific standards of care. Given the strong clinical trial activities for PCNSL in Germany, the PCNSL conference held in Tubingen aimed at comparing the diverging trial strategies in Germany and at exploring the options for joint activities of the various PCNSL study groups in the near future.

Antineoplastic Agents↗
PubMed2005

Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

PURPOSE: To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA. MATERIAL AND METHODS: A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered. RESULTS: Three main CT findings were identified: small nodules (<1cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy+/-segmental 26% (12/46), or peribronchial distribution+/-tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying "halo" sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary hemorrhage occurred in 19% (9/46) of IPA episodes. CONCLUSION: Initial CT findings of invasive pulmonary aspergillosis consist mainly of small nodules or patchy consolidations, showing in 82% of cases an early halo sign. Serious pulmonary hemorrhage was an infrequent clinical complication in our series, with an attributable mortality of 4.3%. IPA-related lethality was 26%, in our cohort. None of the early HRCT signs seemed to predict outcome.

Adolescent↗
PubMed2005

Infectious pulmonary complications after stem cell transplantation or chemotherapy: diagnostic yield of bronchoalveolar lavage.

Hematologic patients are at high risk for infectious pulmonary complications after stem cell transplantation (SCT) or chemotherapy. The aim of this study was to detect the range of pulmonary pathogens in these patients, analyzing 95 bronchoalveolar lavage (BAL) samples with classic and molecular (polymerase chain reaction [PCR]) detection methods. Human cytomegalovirus (HCMV) was detected in 33, herpes simplex virus in 21, human herpesvirus 6 in 24, and other viruses in 16 samples. Aspergillus species were detected in 19, Candida species in 25, and Gram-positive bacteria in 29 samples. The additional use of PCR detection methods increased the diagnostic yield from 56% to 73%, especially concerning viral and fungal infections in BAL samples. No infectious agent was detected in 26 samples. Interestingly, a high incidence of polymicrobial infections (50/95) was detected, dominated by HCMV co-infections, especially after allogeneic SCT. Within 3 years of follow-up, a poor outcome of co-infections of Aspergillus species with HCMV in 9 of 10 cases could be documented, whereas only 7 of 20 patients died with noninfectious BAL results. Herpesviruses, fungi, and Gram-positive bacteria were detected most frequently, and in 53%, polymicrobial infections were diagnosed.

Adult↗
PubMed2005

Fludarabine may induce durable remission in patients with leptomeningeal involvement of chronic lymphocytic leukemia.

Leptomeningeal involvement (LI) is a rare complication in the course of B-cell chronic lymphocytic leukemia (CLL). It is difficult to assess, thus several cases may go unrecognized. Here we report on six patients with LI of B-CLL. Neurologic symptoms were present in five of six patients. Cerebral MRI, although performed in all subjects, was diagnostic in two patients only. Examination of cerebrospinal fluid by cytology and immunophenotyping revealed LI in all six cases. One patient received whole brain irradiation, two patients received intrathecal therapy or intravenous fludarabine respectively. Clinical responses occurred in one patient after irradiation and two patients after fludarabine. Response in CSF was observed in all four evaluable patients after intrathecal therapy (n=2) and fludarabine (n=2). Survival for the patient who received irradiation was five months and for the two patients treated with intrathecal therapy three and six months respectively. One of the patients on fludarabine treatment survived for 21 months with an 11 month event-free survival for the CNS manifestations while the other patient has been in an ongoing meningeal CR and hematologic PR for 20 months. We conclude that fludarabine may be useful in meningeal involvement of CLL with impact on systemic disease.

Adult↗
PubMed2005

Mucormycoses in patients with hematologic malignancies: an emerging fungal infection.

BACKGROUND AND OBJECTIVES: Mucormycoses are seen with an increasing incidence in immunocompromised patients. Most common presentations are rhinocerebral and pulmonary. We here report the experience of a single center with mucormycoses in patients with hematologic malignancies. RESULTS: Mucormycoses were diagnosed in six patients, (median age of 52 years; range, 26-74) treated between 2001-2004. Diagnoses included acute myeloid leukemia (AML) (n=3), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1) and multiple myeloma (n=1). Mucormycosis was diagnosed in the neutropenic state following allogeneic hematopoietic cell transplantation (n=3) or intense chemotherapy (n=3). Sites of infections were rhinocerebral, facial and pulmonary involvement in one patient each and disseminated mucormycosis in three patients. The diagnosis was established by computed tomography followed by surgical interventions and histological diagnosis in 4 patients and post-mortem in two patients. Species identified were Rhizopus (n=3), Rhizomucor (n=2) and Absidia (n=1). Treatment responses were best if surgical resection was followed by aggressive antifungal chemotherapy. Five of six 6 patients died, all of complications of mucormycosis or their underlying disease. Only one patient with facial mucormycosis is still alive. CONCLUSIONS: This experience demonstrates that patient with mucormycoses have a high mortality rate and early recognition followed by aggressive surgical debridement, high dose antifungal therapy and attempts to correct the underlying immunocompromised state are crucial in the treatment of this fatal infection.

Adult↗
PubMed2004

Fatal immune-mediated pancytopenia and a TRALI-like syndrome associated with high titers of recipient-type antibodies against donor-derived peripheral blood cells after allogeneic bone marrow transplantation following dose reduced conditioning.

Pancytopenia occurring after bone marrow transplantation is a rare complication. A 47 year old patient with progression of multiple myeloma after standard therapy received an allogeneic marrow graft from a matched unrelated donor. The non-myeloablative conditioning regimen consisted of fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and total body irradiation. GVHD prophylaxis consisted of cyclosporine. Neutrophil engraftment was as expected and the patient was discharged without signs of acute GvHD. On day +34 the patient presented with clinical and laboratory findings consistent with severe pancytopenia. Antibodies against red cells, platelets, lymphocytes and granulocytes were detected in extremely high titers. Immune-mediated pancytopenia was refractory on multiple immunosuppressive treatment strategies. Proliferation of polyclonal plasma cells of recipient-type that was documented postmortem, was most likely responsible for excessive antibody formation.

Anemia, Hemolytic, Autoimmune↗
PubMed2004

CMV-specific immunotherapy.

Considerable progress has been made in our understanding of the immunobiology of infections in immunocompromised hosts. Insights derived from animal model and human studies have provided the rationale to investigate immunotherapy with alphabeta+ T cells to restore responses considered essential for protective immunity to cytomegalovirus infection. Future studies will address the role of adoptive immunotherapy using different immunoeffector cell populations to improve control of virus infection. The use of genetically modified T cells has already been evaluated clinically and offers the potential for improving safety and efficacy and removing obstacles to successful immunotherapy. Although these studies are in the early stages and present considerable technical challenges, the results suggest that cellular immunotherapy will be a fruitful area for investigation in future years.

Adoptive Transfer↗
PubMed2004

Clinical aspects of CMV infection after stem cell transplantation.

Cytomegalovirus (CMV) infection is one of the most important infectious complications after stem cell transplantation (SCT). Major improvements in the management of CMV infection have been achieved during the last decade, including the introduction of safe blood product support for CMV-seronegative patients, the development of early pre-emptive antiviral therapy based on sensitive diagnostic tests, and antiviral prophylaxis. With the better control of CMV infection during the first 100 days after allogeneic SCT an increase in the incidence of CMV infection and disease after day 100 after transplantation was observed. New methods that allow for the reconstitution of CMV-specific immune responses such as adoptive T-cell therapy are promising tools that might help to improve the management of late CMV infection and disease.

Antiviral Agents↗
PubMed2004

Preliminary evaluation of one conventional nested and two real-time PCR assays for the detection of Toxoplasma gondii in immunocompromised patients.

Toxoplasma reactivation is a serious complication in patients receiving allogenic stem cell transplantation. Real-time PCR assays allow a rapid diagnosis of toxoplasma infection; however, no comparative data are available on the performance of real-time PCR protocols under routine conditions. Therefore, the aim of this study was to amplify Toxoplasma gondii DNA from routine samples of allogenic stem cell recipients using two real-time PCR assays on a LightCycler, and using conventional nested PCR. Conventional nested PCR revealed T. gondii DNA in 16 samples. Only 12 of the 16 samples yielded a positive result in both real-time PCRs. The accuracy of the conventional PCR results was demonstrated by direct sequencing. Amplification and detection of the amplicon was completed in only 1 h using the real-time PCR assays. Thus, real-time PCR substantially accelerates the detection of T. gondii DNA in the majority of positive specimens; however, conventional nested PCR is required for detection of T. gondii DNA in some samples.

Animals↗
PubMed2004

Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4.

Invasive aspergillosis (IA) is a leading cause of mortality in haematological patients. Appropriate activation of the innate immune system is crucial for the successful clearance of IA. Therefore, we studied the Aspergillus fumigatus-mediated activation of human granulocytes and monocyte-derived immature dendritic cells (DCs), as well as murine bone marrow-derived DCs (BMDCs) from wild type, toll-like receptor (TLR)4-deficient, TLR2 knockout, and TLR2/TLR4 double deficient mice. Aspergillus fumigatus antigens induced the activation and maturation of immature DCs as characterized by CD83 expression, upregulation of major histocompatibility complex and co-stimulatory molecules. Moreover, fungal antigens enhanced the phagocytosis and production of interleukin (IL)-8 in granulocytes. The release of IL-12 by BMDCs in response to A. fumigatus antigens was dependent on the expression of TLR2, whereas the release of IL-6 was dependent on the expression of functional TLR4 molecules. The protein precipitate of A. fumigatus supernatant provided strong stimulation of DCs and granulocytes, indicating that a factor secreted by A. fumigatus might activate innate immune cells. In conclusion, A. fumigatus antigens induced the activation of DCs and granulocytes. Our results indicated that this activation was mediated via TLR2 and TLR4. Future studies are needed to assess the clinical impact of these findings in patients at high risk for IA.

Animals↗
PubMed2003

Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation.

Humans↗