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H Einsele

Publications and source records attributed to H Einsele.

At least 37 records · Page 2Linked to original sources
PubMed2003

Diagnosis of invasive fungal infections in hematology and oncology--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

Hematology↗
PubMed2003

Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Adenovirus is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation and there is no established therapy. Cidofovir has in vitro efficacy against adenovirus. We performed a retrospective analysis of 45 patients treated with cidofovir for adenovirus from 10 centers. In total, 16 patients had definite adenovirus disease, 13 probable disease, and 16 asymptomatic infections. A total of 31 (69%) patients were successfully treated with cidofovir, 10 failed, and four were not evaluable owing to early death from other causes. Cidofovir therapy was successful in 10 patients with adenovirus disease, 10 patients with probable disease, and in 10 patients with asymptomatic infections. The overall survival at 28 days and 6 months after initiation of cidofovir therapy was 76 and 46%, respectively. Of the patients, 18 developed toxicity associated with cidofovir: 14 developed renal toxicity and four other types of toxicities. We conclude that cidofovir may be useful against adenovirus after allogeneic hematopoietic stem cell transplantation but additional studies are needed.

Adenovirus Infections, Human↗
PubMed2003

Severe acute graft-versus-host disease after T-cell depleted allogeneic stem cell graft from a second donor caused by persisting T-cells from the first donor.

HLA disparity is a major risk factor for graft rejection and GVHD. We report a patient with CML (accelerated phase) who underwent allogeneic SCT from a mismatched unrelated donor and developed acute GVHD. With immunosuppression, GVHD symptoms improved but graft rejection occurred. After a second conditioning regimen, the patient received a second graft from a haploidentical related donor. Engraftment occurred, but the patient died from GVHD and pulmonary aspergillosis. Chimeric analysis revealed that all leukocytes were of donor 2 origin apart from CD3+ T cells, which were 100% donor 1 type. Thus, in spite of intensified immunosuppression and successful transplantation of a second graft, T cells from the first donor persisted and induced severe acute GVHD.

Acute Disease↗
PubMed2003

Successful haematopoietic stem cell transplantation from a matched unrelated donor following three graft failures from HLA-mismatched related donors.

Graft rejection and graft failure are serious complications after allogeneic stem cell transplantation (SCT). We report a patient with CML in first chronic phase who finally engrafted with a transplant from an HLA-identical unrelated donor after graft failures from two related HLA-mismatched sibling donors. After failure of one BM and two PBSC grafts from two 1 HLA-antigen mismatched related donors, the patient was finally successfully transplanted from a subsequently identified HLA-identical unrelated donor (donor 3). At 5 years post transplant, the patient is in complete cytogenetic and molecular remission.

Adult↗
PubMed2003

A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma.

The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32-60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade >I in 75% of patients. Three patients developed reversible veno-occlusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.

Adult↗
PubMed2003

Blood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma.

High-dose chemotherapy with autologous peripheral blood stem cell transplantation is the standard treatment of patients with multiple myeloma today. In this study we used a combination mobilizing chemotherapy containing ifosfamide with G-CSF before stem cell collection. The chemotherapy regimen consisted of ifosfamide (2,500 mg/m(2) days 1-3), epirubicin (100 mg/m(2) day 1) and etoposide (150 mg/m(2) days 1-3) followed by G-CSF (5 mug/kg from day 5). In 30 younger patients (median age 51 years; range 41-60 years) who received the IEV regimen in 100% dosage, a median of 11.15 x 10(6) CD34(+) cells/kg (range 0-44.60 x 10(6) CD34(+) cells/kg) was collected. In 22 elder patients (median age 64 years; range 59-72 years) similar collection results were obtained with a median of 10.82 x 10(6) CD34(+) cells/kg (range 0.99-42.22 x 10(6) CD34(+) cells/kg) after the IEV regimen in 75% dosage. The pretreatment chemotherapy cycles before mobilization were fewer in elder patients with a median of 0 cycles (range 0-7 cycles) compared with younger patients with a median of 4 cycles (range 0-7 cycles). These collection results were favorable and allowed to support a tandem transplantation procedure in younger and elder patients in 97 and 95%, respectively. In the majority of patients, the hematological toxicity of IEV was of WHO grade 3/4. The extramedullary toxicity was mild to moderate and there were only few cases (5-10%) of relevant nephrotoxicity or neurotoxicity associated with the application of ifosfamide.

Adult↗
PubMed2002

Correlations between hematopoietic progenitor cell counts as measured by Sysmex and CD34+ cell harvest yields following mobilization with different regimens.

PURPOSE: The Sysmex SE-9000 cell counter provides an estimate of immature cells referred to as hematopoietic progenitor cells (HPC). HPC counts should correlate with CD34+ counts in mobilized peripheral blood and apheresis to allow optimization of apheresis timing. METHODS: We correlated the HPC counts as measured in the immature information channel with CD34+ cell levels as determined by FACS (HPCA-2 antibody, Becton Dickinson) from mobilized peripheral blood in 40 samples (27 patients and three healthy donors) and in aphereses ( n=113, 41 patients and 20 healthy donors). RESULTS: In mobilized blood, HPC counts were correlated with CD34+ cells ( r=0.78, P<0.0001, n=40). The HPC counts were about 1.5-fold higher than CD34+ cell counts with a median (range) of 84 (1-747)/microl and 57 (1-370)/microl, respectively. In CD34+ selected cell preparations ( n=8), HPC counts were about fourfold lower than CD34+ cell counts with a median (range) of 179 (67-693)/microl and 760 (191-4309)/microl, respectively. In apheresis preparations, linear regression analyses were performed for the group of stem cell donors ( n=44), the group of lymphoma patients ( n=23), the multiple myeloma group ( n=21), and the group of solid tumors ( n=25). Interestingly, no correlation between HPC counts and CD34+ cell counts was found in the G-CSF-mobilized healthy donor group ( r=0.23, P=0.13). Pairing of HPC counts and CD34+ counts was effective in the group of patients receiving chemotherapy + G-CSF for stem cell mobilization: lymphoma group ( r=0.67, P=0.0005), multiple myeloma group ( r=0.56, P=0.008), and the group of solid tumors ( r=0.52, P=0.007). CONCLUSIONS: Lymphoma and multiple myeloma patients who were moderately pretreated and mobilized with chemotherapy and G-CSF showed the best results in correlation analyses even at low HPC counts. Therefore, HPC measurement can be used for timing of apheresis in these patients.

Adolescent↗
PubMed2002

Successful antiviral treatment for fulminant reactivated hepatitis B after autologous stem cell transplantation and prophylaxis during subsequent allogeneic stem cell transplantation.

The risk of severe hepatic damage due to reactivation of hepatitis B virus (HBV) infection after intensive myelosuppressive chemotherapy is well known. Two of the most evolved nucleotide analogues showing good activity against the hepatitis B virus are lamivudine and famciclovir. We report the successful therapeutic use of lamivudine and famciclovir for fulminant reactivated hepatitis B after autologous peripheral blood stem cell transplantation (PBSCT) and the subsequent prophylactic use of lamivudine during allogeneic blood stem cell transplantation (alloSCT) for chronic lymphocytic leukemia (CLL) in a 40-year-old patient. Antiviral therapy was well tolerated and no hematotoxicity occurred. Our observation warrants further investigation of antiviral therapy with famciclovir and lamivudine in HBV carriers receiving intensive myelosuppressive chemotherapy.

2-Aminopurine↗
PubMed2002

Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation.

Preemptive treatment based on the sensitive detection of CMV-DNA has helped to reduce HCMV-related mortality after allogeneic stem cell transplantation (SCT). Detection of active viral replication might help to better predict HCMV disease. In this study, 33 recipients at risk for HCMV infection after allogeneic SCT were prospectively monitored 1x/week for active HCMV infection by NASBA, whole blood DNA-PCR and virus culture assays. Preemptive antiviral therapy was initiated after the second positive PCR result, while NASBA results were not considered for clinical decision-making. Overall, a high agreement between PCR and NASBA on a per sample (85.3%) and per patient (87.9%) level was demonstrated. HCMV DNA titers in the blood were found to be higher in PCR(+)/NASBA(+) compared to PCR(+)/NASBA(-) samples (P < 0.01). None of the NASBA-negative patients developed HCMV disease. Sixteen of 18 patients receiving PCR-based preemptive therapy were also found NASBA positive. There was no difference between the assays for the time to the first positive test result. However, the time to the first negative test result upon initiation of antiviral therapy was significantly shorter for the NASBA assay (P = 0.002), indicating a high positive predictive value to assess the efficacy of antiviral therapy. Three patients developed late-onset HCMV disease, all of whom were found to be PCR and NASBA positive. In conclusion, the data presented clearly demonstrate the value of patient monitoring using the NASBA assay to early diagnose active HCMV infection and to assess the efficacy of antiviral therapy in high risk patients after allogeneic SCT. A prospective comparison of PCR-based vs NASBA-based preemptive therapy is ongoing.

Adolescent↗
PubMed2002

Induction of CMV-specific T-cell lines using Ag-presenting cells pulsed with CMV protein or peptide.

BACKGROUND: CMV disease is still associated with a high morbidity and mortality in recipients of a solid organ or stem cell graft, especially in patients undergoing allogenic stem cell transplantation. Reconstitution of CMV-specific CD4(+) and CD8(+) cytotoxic T cell responses are essential to control CMV infection following allogenic stem cell transplantation. The transfer of unselected populations of lymphocytes from the peripheral blood of a CMV-scropositive donor to a transplant recipient can be used to control CMV infection. However, such transfer of unselected donor lymphocytes is limited by potentially fatal complications that arise from alloreactive T cells, also present in the unselected donor lymphocytes. Thus to make infusion of donor T cells safe and also more effective in controlling CMV infection in the recipient of the T cell infusion, T cells are manipulated in vitro to deplete alloreactive T cells and to enrich for CMV-specific T cells. METHODS: Using various antigen-presenting cells (monocytes/PBMNCs/dendritic cells) and different modes of antigen presentation (infected APCs, pulsing of protein or peptide antigen) different CMV-specific T cell populations can be generated and expanded. RESULTS: Using protein-/or peptide-pulsed DCs CMV-specific CD8(+) cytoxic T cell lines (can be generated and expanded) in addition CMV-specific CD4(+) T cell lines can be generated when CMV-protein-pulsed DCs are used as antigen-presenting cells. When peripheral blood mononuclear cells were stimulated with CMV lysates predominantly CMV-specific CD4(+) T cells are generated and expanded ex vivo. DISCUSSION: Depending on the APC used (monocytes versus DC) and the mode of antigen presentation (protein versus peptide pulsing) different CMV-specific T cell populations of varying purity can be generated which show preserved function when tested for specific proliferation, cytokine production and cytotoxicity.

Antigen Presentation↗
PubMed2001

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗
PubMed2001

Survival after bone marrow transplantation from cytomegalovirus seropositive sibling donors.

HLA-A2-restricted T cells show peptide-specific activity against cytomegalovirus and leukaemia cells. We retrospectively analysed the influence of donor cytomegalovirus serostatus on the outcome of 103 consecutive patients who had leukaemia and who received bone-marrow transplants from HLA-identical sibling donors. We found that donor cytomegalovirus seropositivity significantly improved overall survival (p=0.02) as a result of lower relapse incidence (p=0.035) in HLA-A2-positive but not HLA-A2-negative recipients. In HLA-A2-positive recipients donor cytomegalovirus seropositivity was associated with chronic graft-versus-host disease (GVHD), but even in patients without chronic GVHD donor cytomegalovirus seropositivity significantly improved survival (p=0.0483). These preliminary data provide evidence that at least in HLA-A2-positive recipients, transplantation of bone marrow from cytomegalovirus positive, HLA-identical sibling donors seems to be associated with substantial graft-versus-leukaemia activity, and suggests a cross-reactivity of cytomegalovirus-specific donor-derived cytotoxic T cells with HLA-A2-restricted recipient minor histocompatibility antigens.

Adolescent↗
PubMed2001

Molecular pathogenesis of Epstein-Barr virus associated posttransplant lymphomas: new insights through latent membrane protein 1 fingerprinting.

BACKGROUND: Fingerprint amino acid patterns within the carboxy terminus of the latent membrane protein (LMP1) oncoprotein of Epstein-Barr virus (EBV) allow individual strain identification at the molecular level. LMP1 is expressed in the tumor cells of EBV-associated posttransplant lymphomas (PTLs) and the LMP1 genome is also identified in lymphocytes of most donors of allogeneic bone marrow. Therefore, LMP1 genotyping in donor lymphocytes and PTL tumor cells, together with sex chromatin determination of tumor cells, allows to determine the origin of PTL tumor cells and the origin of individual EBV strains harboured by them. METHODS: We traced the origin of aggressive PTLs occurring in six patients after allogeneic T cell-depleted stem cell transplantation (allo-SCT). DNA was extracted from donor lymphocytes and PTLs of recipients and amplified with LMP1-specific primers in each case. A comparative sequence analysis of the fingerprint LMP1 region identified in donor lymphocytes and lymphoma was performed. RESULTS: One lymphoma of donor origin occurred after highly selected CD34+ PBSCT and contained the same LMP1 genotype as the donor lymphocytes. Three lymphomas of recipient origin had deletions within the carboxy terminus of LMP1, not identified in the donor strains. All lymphomas occurred in the setting of allo-SCT and had a rapid clinical course. CONCLUSIONS: These results show that highly selected CD34+ PBSCT does not protect against transfer of EBV positive founder cells of donor type PTL and that, after allo-SCT, recipient type PTLs are not uncommon. Outgrowth of recipient type lymphoma may be favoured by LMP1 deletion variant strains present in recipient lymphocytes.

Adult↗