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Biomedical subjects

W Linkesch

Publications and source records attributed to W Linkesch.

At least 73 records · Page 4Linked to original sources
PubMed1996

High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

PURPOSE: To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS: Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS: The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION: Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis.

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.

Adult↗
PubMed1995

Hodgkin's disease developing after spontaneous remission of chronic lymphocytic leukemia.

We present a 71-year-old patient with chronic lymphocytic leukemia diagnosed 27 years ago. Initially, the disease was staged as Rai II and the patient suffered from secondary immunoglobulin deficiency. Nevertheless, no treatment was necessary at that time. Because of disease progression a single course of chemotherapy was given in 1984. During the following year there was a constant decline of the WBC, accompanied by normalization of the immunoglobulins; both have remained stable ever since that time. However, there was still residual bone marrow infiltration, indicating persisting CLL. In 1993 cervical lymphadenopathy occurred with acute onset. A diagnostic lymphadenectomy revealed Hodgkin's disease of the nodular-sclerosing subtype. The patient was staged as II-III according to the Ann Arbor Classification and underwent radiation therapy. Cytogenetic examination of the bone marrow revealed a normal karyotype with an inversion of chromosome 9. This case demonstrates the rate coincidence of two lymphoproliferative disorders in the same patient. The clinical course and the immunologic findings of this patient are presented, together with a review of the literature.

Adult↗
PubMed1995

In vivo administration of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor increases neutrophil oxidative burst activity.

The influence of CSF therapy on the superoxide (O2-) releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) of neutrophils from 32 patients with testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was assessed: 8 patients were treated as control group without CSF therapy, 12 patients received GM-CSF, and 12 patients received G-CSF. To monitor the kinetics of the respiratory burst, leukocytes were collected before initiation of chemotherapy and ABMT, during CSF administration on days 1 and 3 after leukocyte recovery, and 7 days after leukocyte recovery (controls) or 3 days after the end of CSF therapy. Neutrophils from patients who received GM-CSF showed a significantly higher superoxide anion release compared with control patients (p < 0.001). O2- production in these patients was higher than that achieved by in vitro preincubation of neutrophils from control patients. Increased burst activity was seen only during infusion of GM-CSF and returned to pretherapeutic values after the end of GM-CSF administration. A similar but less pronounced increase was seen in patients who received G-CSF. In vitro preincubation of neutrophils from the same patients with GM-CSF, G-CSF, or TNF showed that O2- production by neutrophils from patients receiving GM-CSF could not be further enhanced, whereas O2- production by neutrophils derived from patients receiving G-CSF could be further augmented by TNF but not by GM-CSF. Interestingly, neutrophils from patients treated with GM-CSF but not those with G-CSF therapy retained a higher response to in vitro stimulation with GM-CSF or TNF after the end of CSF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Influence of in vivo administration of GM-CSF and G-CSF on monocyte cytotoxicity.

The influence of colony-stimulating factors (CSFs) on the monocyte functions of 32 patients with refractory testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was tested. Eight patients were treated as a control group without CSF therapy, 12 patients received recombinant human granulocyte-macrophage-CSF (rhGM-CSF), and 12 patients received recombinant human granulocyte-CSF (rhG-CSF). For the assessment of monocyte activation induced by CSF expression of major histocompatibility complex (MHC) class I and II antigens, production of tumor necrosis factor (TNF) and monocyte-mediated cytotoxicity against tumor cell targets were chosen. Monocytes from patients with GM-CSF therapy showed a significant increase in MHC class I and II antigen expression as compared to patients without CSF treatment (p < 0.001). A significant increase in the expression of MHC class I was seen in monocytes from patients under G-CSF treatment, whereas no change of class II antigens was noticed. Production of TNF and monocyte-mediated cytotoxicity against U937 tumor cells was significantly increased in monocytes derived from patients receiving GM-CSF, as compared to those from the control group, while no effect was detectable in monocytes from patients with G-CSF therapy. However, after in vitro stimulation with interferon-gamma (IFN-gamma), monocytes derived from GM-CSF as well as from G-CSF treated patients responded with a significantly higher TNF-production and cytotoxicity than monocytes from control patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Collection and long-term preservation of peripheral stem cells].

The methods of collection and storage of peripheral blood stem cells are described, and the harvesting after conditioning with cytokines and/or myelosuppressive therapy is discussed. It could be demonstrated that the combination of cytostatics and cytokines gives the best yield and enables to collect a sufficient amount of peripheral bloodstem cells for a successful engraftment after myeloablative therapy with only few aphereses.

Antineoplastic Agents↗
PubMed1994

Granulocytic sarcoma of the prostate as the first manifestation of a late relapse of acute myelogenous leukemia.

We describe a 68-year-old patient who developed granulocytic sarcoma of the prostate 9 years after complete remission following successful treatment of acute myelogenous leukemia (FAB, M2). PCR analysis of bone marrow samples in first remission and at the time of relapse detected an AML1/ETO rearrangement typical for AMLs with t (8;21). The CD56 antigen was not expressed on the leukemic cells. Systemic chemotherapy led to a short-lasting regression of the tumor, but the patient subsequently developed overt bone marrow relapse and died during chemotherapy. While granulocytic sarcoma as a primary manifestation of AML is well known, as the first manifestation of relapse it appears to be very uncommon.

Aged↗
PubMed1994

AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation.

The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of this method for monitoring and detection of minimal residual disease (MRD) in seven patients who reached a complete hematological remission (CHR) after chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood (PB) samples of five patients in first continuous complete remission (CCR) were still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66 months. Chemotherapy led to a reduction from first- to second-step PCR-positivity in three serially monitored patients. AML1/ETO mRNA was also detected in the PB of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM) showed identical results in all samples tested simultaneously. AML1/ETO fusion transcripts were neither found in the PB and BM of a healthy individual, nor in the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)-leukemia. Our results indicate the presence of cells carrying the AML1/ETO rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT for t(8;21)-positive AML. While this finding raises interesting questions about the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the prediction of impending relapse.

Adult↗
PubMed1994

Early detection of hematopoietic engraftment after bone marrow and peripheral blood stem cell transplantation by highly fluorescent reticulocyte counts.

At present, the appearance of neutrophils in the peripheral blood is considered to be the earliest sign of hematopoietic regeneration after myeloablative chemoradiotherapy. We studied erythroid regeneration in 27 allogeneic and 21 autologous marrow recipients using an automated reticulocyte counter employing a flow cytometric technique. Thereby, reticulocytes can be divided into a high, moderate and low fluorescent fraction according to RNA content. Marrow ablation caused an immediate and rapid fall in highly fluorescent reticulocytes (HFR) to zero in all patients. HFR reappeared after a median time of 7 days after allogeneic and 11 days after autologous marrow grafting. This was 7 and 2 days earlier than the appearance of first neutrophils. In allogeneic marrow recipients given erythropoetin after marrow infusion the median time to reach HFR of 0.2 and 0.5 x 10(9)/l was significantly shorter than time to reach similar absolute neutrophil counts (ANC). In allogeneic marrow recipients treated with G-CSF time to rise of HFR and ANC was almost exactly the same. Thus, automated flow cytometric reticulocyte counting allows early detection of hematopoietic regeneration and may be of clinical value for the early diagnosis of inadequate marrow function after marrow transplantation and the monitoring of erythroid regeneration under cytokine administration.

Adolescent↗
PubMed1993

A rare complication of a central venous catheter system (Port-a-Cath). A case report of a catheter embolization after catheter fracture during power training.

A 36 year old patient received an implantable central venous catheter system for a bone marrow transplantation. One year after the successful transplantation, embolization of the catheter was discovered by a routine x-ray three weeks after beginning of an exercise program with a spring expander including arm exercises. The catheter was removed without further complication via the vena femoralis. We assume that the cause for this incident was material fatigue due to pressure between clavicula and first rib possibly caused by strength training. We suggest as a consequence that patients with an implanted catheter system should before starting exercise consult a sports medicine specialist who would in turn cooperate with the specialist responsible for the catheter, so that an adequate and safe training program can be selected.

Adult↗
PubMed1993

[Collection and long-term preservation of peripheral stem cells].

The methods of collection and storage of peripheral blood stem cells are described and the harvesting after conditioning with cytokines and/or myelosuppressive therapy is discussed. It could be demonstrated that the combination of cytostatics and cytokines gives the best yield and enables to collect a sufficient amount of peripheral blood stem cells for a successful engraftment after myeloablative therapy with only few aphereses.

Antigens, CD↗
PubMed1992

Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.

Forty-five patients with myeloproliferative or myelodysplastic syndromes, treated with recombinant interferon-alpha (rIFN-alpha) for a minimum of 1 up to 4 years, were examined for the occurrence of thyroid autoimmunity. During treatment, the rate of thyroid autoimmunity rose to more than 20%. The decrease in severity and frequency of thyroid autoimmunity after withdrawal of IFN shows that this is a potentially reversible side effect. The key determinant for the manifestation of this IFN-related autoimmune phenomenon seems to be a predisposition for autoimmunity, since patients with initially detectable thyroid antibodies are prone to exacerbations of thyroid autoimmunity. Concurrent with thyroid autoimmunity, hypothyroidism occurred but did not correlate with the levels of thyroid antibodies, although severe hypothyroidism in two patients was accompanied by increased levels of thyroid antibodies. This investigation shows that thyroid autoimmunity and consecutively hypothyroidism must be expected in certain patients treated with rIFN-alpha during long periods. Furthermore, it may be assumed that IFN-alpha does not induce the development of autoimmunity, but rather enhances the levels of pre-existent thyroid antibodies.

Adult↗
PubMed1991

MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.

Adolescent↗
PubMed1991

Phase II study of amonafide in advanced breast cancer.

Twenty-eight patients with advanced breast cancer refractory to prior hormone and/or first-line chemotherapy (with or without anthracycline drugs) were treated with the investigational agent amonafide at a dose of 800 mg/m2 intravenously over 3 hours repeated every 4 weeks. Five objective tumour responses of 5.0 months' median duration were observed in the 20 patients without previous anthracycline exposure, including 1 CR. Leukopenia was the dose-limiting toxicity; though it was generally modest with the 800 mg/m2 amonafide starting dose, an initial dose reduction should be considered in patients with prior radiotherapy and/or bone marrow involvement. Other adverse reactions included nausea/vomiting (53%), phlebitis/erythema along the vein injected (7%), and mild neurotoxic symptoms during the drug administration such as headache, tinnitus, and diaphoresis (21%). Amonafide is an active compound for the treatment of patients with advanced breast cancer and should be considered for further evaluation and incorporation in combination chemotherapy.

Adenine↗
PubMed1991

Interferon in essential thrombocythaemia.

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.

Adult↗