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Biomedical subjects

W Linkesch

Publications and source records attributed to W Linkesch.

At least 37 records · Page 2Linked to original sources
PubMed2002

Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide.

OBJECTIVES: Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). PATIENTS AND METHODS: We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. RESULTS: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrhythmias were not observed. CONCLUSIONS: These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy.

Adult↗
PubMed2002

Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation.

We assessed long-term outcome in 155 patients who had undergone an allogeneic/syngeneic stem cell transplant (SCT) and were in complete remission for more than 2 years after transplant. Probability of late transplant-related mortality was 6%, and affected only patients with chronic graft-versus-host disease (cGVHD). Thirteen percent of patients experienced relapse. Overall survival projected at 10 and 15 years was 83% and 76%, respectively. Secondary malignancies occurred in two patients, 7.5 and 11 years after SCT. Three female and four male patients parented children 19 to 84 months after SCT. Quality of life (QoL) was assessed in a cross-sectional study by the means of a 30-item questionnaire (QLQ-C30) of the EORTC. The questionnaire was sent to 127 patients remaining alive and answered by 106 patients. Seventy-three percent reported a good to very good QoL within 5 years after SCT and 78% after this time point. However, patients with cGVHD had significant impairment of physical, role and social functioning and only 60% of them were fit for work. These results from long-term survivors show that high cure rates with good to very good QoL can be achieved by allogeneic or syngeneic SCT.

Adolescent↗
PubMed2001

Hepatic veno-occlusive disease in two patients with relapsed acute myeloid leukemia treated with anti-CD33 calicheamicin (CMA-676) immunoconjugate.

Monoclonal antibodies recognizing hematopoietic antigens are increasingly being used to target therapy directly at leukemic cells, with the aim of achieving sustained remission with little systemic toxicity. Administration of anti-CD33 calicheamicin immunoconjugate is commonly regarded as being safe, with only moderate systemic non-hematological side effects. We report on two cases of hepatic veno-occlusive disease in heavily pretreated patients presenting with relapsed acute myeloid leukemia (AML). Since significant liver toxicity prevented further specific therapy in both patients, we recommend that antibody therapy with anti-CD33 immunoconjugate should be applied with caution in patients presenting with risk factors for the development of hepatic veno-occlusive disease.

Acute Disease↗
PubMed2001

Cytomegalovirus diagnosis in renal and bone marrow transplant recipients: the impact of molecular assays.

BACKGROUND: Cytomegalovirus (CMV) infections are a major threat in transplant recipients. In recent years, new assays for routine CMV diagnosis, based on molecular techniques, have become available. OBJECTIVE: The impact of molecular assays for CMV diagnosis in transplant recipient was evaluated. STUDY DESIGN: A total of 51 transplant recipients were screened for CMV infection. Serological (AxSYM CMV IgG and recombinant CMV IgM assays), antigenemia, CMV DNA (qualitative in house PCR and the quantitative COBAS AMPLICOR CMV MONITOR Test), and CMV mRNA (NucliSens CMV pp67 Test) tests were compared. RESULTS: In 11/20 bone marrow transplant (BMT) recipients and 10/31 renal transplant (RTX) recipients there was no evidence of active CMV infection. Ten RTX recipients and one BMT recipient were antigenemia positive, 21 RTX and seven BMT recipients were PCR positive (qualitative CMV PCR). There were more BMT recipients CMV DNA positive in serum (7/21) than antigenemia positive (1/21). CMV mRNA was found positive in two BMT recipients (one case with no other evidence of CMV infection, the other one CMV DNA positive and antigenemia negative). The only antigenemia positive BMT recipient was found negative for CMV mRNA, but positive in all other tests. Eight RTX recipients were found positive for CMV mRNA. Six of them were also antigenemia positive and five of those were also found positive for CMV IgM. One CMV mRNA positive RTX recipient was CMV IgM positive but antigenemia negative and the other one CMV mRNA positive RTX recipient was found negative in all other tests. Two antigenemia positive RTX recipients were found negative for mRNA and CMV IgM. CONCLUSION: Antigenemia was found to be a good screening test for CMV infection in RTX recipients. In BMT recipients, tests based on molecular techniques appeared to be superior compared to antigenemia.

Adolescent↗
PubMed2001

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Adult↗
PubMed2001

Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

Aged↗
PubMed2000

Complete remission of generalized relapsed extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type of the gastrointestinal tract after high-dose chemotherapy and autologous peripheral stem cell transplantation.

Due to their homing properties, extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type remain localized for long periods of time, and therefore have an excellent prognosis. However, if generalization and/or transformation into a diffuse large-cell lymphoma occurs, the prognosis deteriorates and no established treatment concepts are yet available. We report about a 57-year-old female patient with relapsed transformed stage-IV extranodal MZBL of MALT type of the entire gastrointestinal tract who was successfully treated using salvage chemotherapy followed by BEAM conditioning [BCNU 1,3-bis-2-(chloroethyl-1-nitrosourea), etoposide, cytosine arabinoside, and melphalan] and autologous peripheral stem cell transplantation. Follow-up revealed a sustained complete remission for 22 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Acute myelofibrosis: multifocal bone marrow infiltration detected by scintigraphy and magnetic resonance imaging.

Acute myelofibrosis is a rare, malignant hematological disorder of unknown etiology with an inevitably fatal outcome. Here we present the study of a 63-year-old Caucasian man with acute onset of pancytopenia. Repeated bone marrow biopsies showed dense fibrosis and hypoplastic hematopoiesis raising various differential diagnoses of malignant and nonmalignant conditions. Bone marrow scintigraphy and magnetic resonance imaging (MRI) showed areas suggesting neoplastic infiltration, mainly in both femurs and tibias. Histological examination of a surgical biopsy of the left tibia revealed acute megakaryoblastic leukemia. As the patient refused polychemotherapy, therapy with interferon gamma was initiated but discontinued prematurely because of intolerable side effects. The presented case therefore suggests that the combination of bone marrow scintigraphy and MRI is a valuable diagnostic tool in patients presenting with myelofibrosis of unknown origin.

Acute Disease↗
PubMed2000

Treatment of patients with advanced chronic myelogenous leukemia with interferon-alpha-2b and continuous oral cytarabine ocfosfate (YNK01): a pilot study.

The efficacy of continuous oral cytarabine ocfosfate (YNK01) (300 mg/day) in combination with interferon alpha (IFNalpha, 5x10(6) IU/day) was evaluated in patients with advanced chronic myelogenous leukemia, who previously failed to respond to IFNalpha-based therapies. Dose escalations up to 900 mg YNK01 were allowed in patients who failed to respond. In view of our results, four patients developed a complete hematological response after YNK01 was started. Among those who initially responded to YNK01, one complete cytogenetic response was achieved 18 months later. Although the data are preliminary, this is the first study showing that continuous administration of YNK01 along with IFNalpha is effective in patients with advanced chronic myelogenous leukemia.

Adult↗
PubMed2000

Extramedullary T cell lymphoblastic transformation of chronic myeloid leukaemia successfully treated with matched unrelated donor bone marrow transplantation.

Chronic myeloid leukaemia (CML) inevitably terminates in blast crisis (BC) which is of myeloid phenotype in approximately two-thirds and B-lymphoid in one-third of patients. T cell BC is rare and associated with poor prognosis. We describe the case of a 48-year-old woman with extramedullary T cell lymphoblastic transformation. After treatment with combination chemotherapy she achieved a second chronic phase and underwent an allogeneic BMT from an HLA-matched unrelated donor. At 30 months follow-up she is still in complete molecular remission and in good clinical condition. We conclude that unrelated donor BMT should be considered as a therapeutic option for patients with extramedullary BC.

Blast Crisis↗
PubMed2000

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients.

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.

Adult↗
PubMed2000

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B.

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.

Administration, Oral↗
PubMed2000

[Stem cell transplantation in germ cell tumors].

High dose chemotherapy (HDCT) with autologous stem cell transplantation in patients with relapsed or refractory non-seminomatous germ cell tumors seems to be the only therapeutic option with curative intention. Evaluation of a scored risk profile before HDCT might significantly support the precise estimation of results after HDCT. Patients with a negative or low score could achieve long-lasting complete remissions or might be cured, whereas patients with absolutely refractory disease do not benefit from HDCT. Ongoing prospective randomised trials in Europe and USA comparing standard therapy with HDCT will hopefully contribute to the right therapeutic decision in the future.

Antineoplastic Combined Chemotherapy Protocols↗