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Biomedical subjects

H Baurmann

Publications and source records attributed to H Baurmann.

At least 19 recordsLinked to original sources

ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML).

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.

Acute Disease↗

Skin involvement as the first manifestation of systemic aspergillosis in patients after allogeneic hematopoietic cell transplantation.

Skin involvement due to a systemic infection with Aspergillus species in the course of allogeneic hematopoietic cell transplantation is extremely rare. We report the clinical course of two patients with hematologic malignancies who underwent allogeneic hematopoietic cell transplantation (HCT) and developed disseminated skin involvement as the first clinical symptom of a proven systemic Aspergillus infection.

Adult↗

Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

Little is known about the mechanisms and the kinetics of the so-called graft-versus-leukemia (GVL) response induced by donor lymphocyte infusions (DLI) in patients with leukemic relapse after allogeneic bone marrow transplantation (BMT). We sought to elucidate this problem by sequentially studying three patients with relapsed chronic myeloid leukemia after sex-mismatched BMT from time before donor leukocyte infusion until achievement of complete molecular remission. Lineage-specific chimerism was assessed longitudinally by a combined fluorescent immunophenotyping and sex chromosome-specific in situ hybridization approach. Results were related to quantitative detection of bcr-abl transcripts by competitive differential reverse transcriptase-polymerase chain reaction (RT-PCR), qualitative bcr-abl RT-PCR, and multiplex PCR-based DNA donor/recipient chimerism. All patients had predominant donor lymphopoiesis at the time of DLI, suggesting a state of tolerance to recipient leukemic and/or normal cells. In contrast, granulopoiesis and erythropoiesis were mainly recipient derived in both patients with hematologic relapse and partly recipient derived in the patient with molecular relapse. Eighty percent, 90%, and 8% of CD34(+) cells, respectively, were found to be of recipient origin at relapse, and few donor stem cells predicted for cytopenia post-DLI. Responses were seen after a time lag of 5 to 13 weeks after DLI and resulted in reversal to full donor chimerism within a critical switch period of 4 to 5 weeks. A sudden decrease in recipient cells was paralleled by a sharp decrease in bcr-abl transcript numbers detectable several weeks before achievement of molecular remission and onset of clinical graft-versus-host disease (GVHD). This response pattern was confirmed by retrospective RT-PCR analysis in an additional five patients. Prospective monitoring of stem cell chimerism and response may enable us to individually tailor adoptive immunotherapy in the future.

Adult↗

Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation.

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.

Adult↗

High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.

PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.

Adult↗

Fusarium solani cutaneous infection in a neutropenic patient.

A 47-year-old woman with acute myeloblastic leukemia developed disseminated papules and pustules after chemotherapy. A skin biopsy specimen revealed fungal vasculitis and grew Fusarium solani. The patient died despite treatment with amphotericin B. The isolate was resistant to amphotericin B, imidazole and 5-fluocytosine. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients.

Dermatomycoses↗

Interphase cytogenetics by fluorescent in situ hybridization (FISH) for characterization of monosomy-7-associated myeloid disorders.

By circumventing the need for metaphase preparations, fluorescent in situ hybridization (FISH) on interphase nuclei using chromosome-specific probes is a promising tool for the study of numerical chromosome aberrations not only in proliferating, but also in non-dividing cells. We analyzed 15 cases of monosomy-7-associated myeloid disorders with a biotinylated probe to the (peri)centromeric region of chromosome 7. Monosomy 7 was readily confirmed in all cases during active disease. In two patients only a minority of nuclei was monosomic, whereas cytogenetics had shown all metaphases to be missing one chromosome 7. FISH in one of them was able to identify a small marker chromosome as isolated pericentromeric region of chromosome 7. Minimal residual disease however could not be detected in three remission samples analyzed, as percentages of disomic nuclei were within the range of normal controls (96.8% 2.1%). In order to determine lineage involvement of the monosomic clone, a recent technique combining immunophenotyping and FISH (FICTION) was performed in one patient with AML after MPD. Monosomy 7 was found in virtually all myelomonocytic and erythroid cells (as discriminated by lineage-specific antibodies), in a part of CD34-positive precursor cells, but not in lymphocytes. We conclude that monosomy 7 in this patient is restricted to an early committed progenitor cell capable of erythroid and myelomonocytic differentiation.

Adolescent↗

Acute parvovirus B19 infection mimicking myelodysplastic syndrome of the bone marrow.

A 36-year-old, previously healthy woman was referred to our institution with pancytopenia and splenomegaly for suspected acute leukemia. Bone marrow aspiration showed marked dysplastic changes, excess of blasts, and only spurious red blood cell precursors. Action was taken to prepare allogeneic bone marrow transplantation from an HLA identical sibling for myelodysplastic syndrome. Repeat cytological examination of the bone marrow revealed striking hyperplasia of the red cell line with presence of abnormal giant proerythroblasts. Acute parvovirus B19 infection was suspected and confirmed by detection of anti-B19 IgM and B19 DNA. The underlying disease for this transient aplastic crisis was a formerly unknown hereditary spherocytosis.

Adult↗

Replication of parvovirus B19 in hematopoietic progenitor cells generated in vitro from normal human peripheral blood.

Erythroid progenitor cells generated in vitro from peripheral human blood in the presence of interleukin-3 and erythropoietin were infected with human parvovirus B19. B19 virus DNA replication was highest 48 to 72 h after infection, and maximum levels of B19 virus proteins were detected in culture supernatants at 72 to 96 h after infection. B19 virus propagated in vitro was infectious. This cell culture system with peripheral blood cells facilitates studies in vitro of B19 virus replication.

Blood↗

Productive infection of in vitro generated haemopoietic progenitor cells from normal human adult peripheral blood with parvovirus B19: studies by morphology, immunocytochemistry, flow-cytometry and DNA-hybridization.

Parvovirus B19 exerts a highly selective cytopathic effect on erythroid progenitor cells. Studies so far on the pathogenesis of B19-infection have been performed using bone marrow samples providing large amounts of erythroid progenitor cells. Extensive study, however, has been hampered by the limited access to bone marrow samples. We have designed a liquid culture method allowing the generation of large numbers of erythroid progenitor cells, initiating cultures with CD3- and CD14-poor peripheral blood mononuclear cells. Following a 12 d preincubation in liquid cultures containing recombinant human interleukin 3 (rhIl-3) and recombinant human erythropoietin (rhEpo), cells harvested from the liquid cultures were exposed to B19-containing plasma, followed by a further cultivation in liquid culture for up to 96 h. Cells expressing the CD13 and the glycophorin A (GlyA) antigens, respectively, were monitored sequentially by flow-cytometry, demonstrating a selective inhibition of GlyA-positive cells following B19-inoculation. Typical morphological changes were observed on cytocentrifuge-spots, and typical giant-cells were identified as staining for GlyA. Productive infection by B19 was demonstrable, as B19-DNA increased by about x 100 after 72 h of culture. The liquid culture method generating erythroid target cells for effective infection by B19 virus promises to be a useful and easily accessible tool for further research on B19 infection of haemopoietic cells.

Cells, Cultured↗

Soluble interleukin 2 receptors in patients after bone marrow transplantation.

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft-versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels.

Bone Marrow Transplantation↗

[Fluorescence photometry study of the normal rat retina before and following fluorescein administration].

Semiquantitative fluorescein photometric studies were performed on the retinas of lyophilized rat eyes. Before injecting the fluorescein, the right, dyeless eyes were enucleated under anesthesia with ketamine hydrochloride. The left eyes were removed between 20 seconds and two hours after intravenous injection of fluorescein. Histologic sections of each of the posterior segments were measured fluorophotometrically. The photometric values of most of the fluorescein-dyed retinal sections were higher than those of the contralateral (dyeless) control eyes. With increasing duration of observation the differences between the sections which contained fluorescein and those which did not diminished, although some temporary and limited increases occurred. The higher extinction values of the specimens containing fluorescein are in agreement with the quantitative results of Grimes et al. (1982), who found fluorescein in all retinal layers. Anesthesia-induced acidoses cannot be ruled out may be considered minimal. The information value of quantitative and semiquantative results is certainly superior to qualitative results is certainly superior to qualitative findings.

Animals↗

[Adult T-cell leukemia associated with HTLV1 and positive HIV2 serology in an African woman].

We report a case of acute adult T-cell leukemia associated with HTLV1 infection in a young African woman. The leukemic proliferation consisted of CD4-, CD25-positive lymphoid cells with typically convoluted nuclei and monoclonal integration of the HTLV1-proviral DNA. The clinical course was characterized by a rapid progression of the leukemia with development of hypercalcemia, resistance to chemotherapy, and the presence of multiple opportunistic infections. The additional finding of a seropositivity for HIV2 raises the problem of the respective contribution of the two retroviruses in this patient's disease.

Acquired Immunodeficiency Syndrome↗

[Simultaneous study of ocular vascular reactions of the anterior and posterior segments following clonidine and propranolol in normotensive and hypertensive experimental animals].

The influence of clonidine and propranolol on the vessels of the anterior segment and of the fundus, as well as on mean arterial pressure and heart rate, was investigated in normal rabbits, minipigs, and minipigs with experimentally induced hypertension. The vessel reactions were monitored by photography or fluorescein angiography. Following injection of clonidine, constrictions of episcleral and conjunctival vessels occurred in all the animals, but the fundus vessels of the rabbits were not affected. Difficulties were encountered in assessing the condition of the iris vessels. In minipigs, after administering 6-20 micrograms/kg, an average delay of 2 seconds in the inflow into the retinal vessels was recorded, due possibly to a (transitory?) vessel constriction upstream. Mean arterial pressure increased initially in all animals, but to a different extent in the two species. There was less uniformity as regards heart rate. The vessel reactions of the two species to propranolol were different: in rabbits, a reaction was only observed after administering 2.46 mg/kg bodyweight in episcleral and conjunctival vessels, though not in fundus vessels. Minipigs were given doses of 0.16, 0.5, and 0.8 mg/kg; after 0.5 mg/kg a vessel constriction took place in the episclera and the conjunctiva, becoming manifest after 20 minutes and attaining a maximum after 60 minutes. However, there appeared to be no reaction in the fundus vessels. After an abrupt decrease in mean arterial pressure, both this and the heart rate showed an almost identically slow decrease until the 50th minute, followed by a slight increase up to the 60th minute. The comparison of the circulation parameters reveals some interesting parallels, though also some contrasts. The mechanisms of action and characteristics of these two substances are discussed.

Animals↗

[Simultaneous photography or angiography of anterior and posterior eye segments in experimental animals].

Simultaneous photographic or angiographic studies of the anterior and posterior segments requires a considerable reduction in the respective parts of the negatives; this can be avoided by simultaneous study of the one segment ipsilaterally and the other contralaterally (this can also be performed vice versa). Differences and common properties of the eyes of rabbits and miniature pigs and the human eye are described. Apart from the monkey eye, the pig eye is most readily comparable with the human eye as regards vasotopographic and vasomorphologic conditions. In addition, the courses of angiographies in the eyes of experimental animals were observed; measurements of fluorescein inflow and circulation times in the anterior and posterior segments in miniature pigs are presented. These were subjected to significance tests: only the difference in the inflow and outflow of the dye in retinal vessels was found to be statistically highly significant. The difference in inflow between choroidal and retinal vessels was not significant, though this may have been due to an error of measurement. The techniques and measurements described represent the basis of observation in miniature pigs with experimentally induced hypertension.

Animals↗