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C Aul

Publications and source records attributed to C Aul.

At least 19 recordsLinked to original sources
PubMed2005

Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup.

The survival of patients with myelodysplastic syndromes is strongly affected by chromosomal abnormalities. Patients with an isolated del(5q31) have a favourable prognosis that worsens with the addition of another chromosomal abnormality. It has been reported that both patients with isolated del(5q31) and those with one single additional chromosomal abnormality achieve hematological and cytogenetic remissions with lenalidomide therapy. Whether this translates into improved overall survival of the patient population is unclear. We analysed data of 25 patients with myelodysplastic syndrome and complex chromosomal abnormalities including del(5q31) and show that their median survival is between 7 and 8 months, irrespective of the medullary blast count. Furthermore, we present data of a patient with complex karyotypic anomalies inclusive of del(5q31) treated with lenalidomide who achieved complete cytogenetic remission. This cytogenetic remission was diagnosed after 6 months, and the hematological response is ongoing at 9 months of therapy at a dose of 5 mg p.o. daily. We conclude that lenalidomide has the potential to induce sustained hematological and cytogenetic remissions in the poor prognosis MDS subgroup of del(5q31) patients with complex chromosomal anomalies and that this is likely to improve overall survival.

Adult↗
PubMed2005

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Adolescent↗
PubMed2005

[Anti-angiogenic therapy of a renal angiomyolipoma in a seriously disabled patient suffering from multiple sclerosis].

INTRODUCTION: Angiomyolipoma, although rare, belong together with oncocytomas to the most common benign renal neoplasms. Although angiomyolipoma is usually a non-invasive tumor that does not metastasize, chirurgical intervention, especially in case of large or enlarging tumors, is recommended due to their capacity to cause haemorrhage and other significant clinical complications. CASE REPORT: We report the case of a renal angiomyolipoma in a female patient seriously disabled by multiple sclerosis with reduced physical and nutritional condition. The woman already underwent a nephrectomy 20 years ago due to an angiomyolipoma of the opposite kidney. The patient received oral gefitinib at a dose of 500 mg/day for 28 days. By a four-weekly course of EGFR-inhibitor gefitinib (Iressa), we achieved a control of the angiomyolipoma and were able to prevent nephrectomy. CONCLUSIONS: The use of EGFR inhibitors, whose anti-proliferative activity in renal cell tumors derives not only from direct inhibition of cell proliferation, but also from the inhibition of angiogenesis, requires further investigation.

Administration, Oral↗
PubMed2005

High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study.

We conducted a randomised trial comparing an intensified versus a standard conditioning regimen for high-dose chemotherapy followed by autologous stem-cell transplantation in patients with multiple myeloma. In this study, 56 patients were randomly assigned for high-dose therapy with melphalan 200 mg/m2 or with idarubicin 42 mg/m2, melphalan 200 mg/m2 and cyclophosphamide 120 mg/kg. The primary objective was response rate. Acute toxicity, mainly because of infections, was higher in the intensified treatment arm with a treatment-related mortality of 20% versus 0% in the standard arm. This lead to the early discontinuation of the study. Response rates did not differ significantly between both treatment arms {intensified versus standard: complete response+near complete remission 50% [95% confidence interval (CI) 26-74%] vs. 33% (95% CI 17-55%), partial remission 35% (95% CI 16-61%) vs. 50% (95% CI 30-70%)}. After a follow-up of 5 years, the median time-to-progression and overall survival were not significantly different between both patient groups. Analysis restricted to patients surviving the first 100 d after transplant showed a better outcome for patients with >or=2 bad prognostic risk factors in the intensified treatment arm, however all treatment-related deaths occurred within this group of patients. In conclusion, intensified conditioning for high-dose therapy had intolerably high toxicity without improving outcome in patients with multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Autoimmune disorders in two patients with myelodysplastic syndrome and 5q deletion.

Autoimmune diseases occurring concurrently with myelodysplastic syndrome (MDS) with deletion del(5q) including band q31 are very rare and have only been reported twice in the medical literature. We present two additional cases, one patient with del(5q) and trisomy 21 who suffered from rheumatoid arthritis and one patient with isolated del(5q) and autoimmune hemolytic anemia. Both patients had mild leukopenia and severe transfusion-dependent anemia. The rheumatoid arthritis was treated with antirheumatics without additional immunosuppressive medication. Autoimmune hemolytic anemia was controlled with long-term steroid administration. This patient developed additional trisomy 21, 2 years after the initial diagnosis of del(5q). Contrary to previous reports on autoimmune disorders in MDS mentioning improvements of hematological function in response to steroid administration, neither of our patients had a hematological improvement under corticosteroids.

Adrenal Cortex Hormones↗
PubMed2004

[The competence network "acute and chronic leukemias"].

Leukemias are a challenge and a cost factor to society because of their frequency in all age groups. They also serve as a model for a variety of diseases and possess exemplary relevance for basic research and patient care. Leukemia research and therapy have achieved high standards and even a leading position in Germany with regard to clinical trials, standardization of diagnostics and molecular studies of prognostic factors, signal transduction and gene expression. Progress is hampered, however, by fragmentation of leukemia trial groups, diagnostic approaches and treatment research activities. A network was therefore created to integrate the leading leukemia trial groups on chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphatic leukemia (ALL), myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (CMPD) and their interdisciplinary partners (diagnostics, treatment research, biometry) in cooperation with basic research and pharmaceutical industry to foster advancements in leukemia-related research and health care through clinical trials, promotion of translational research, introduction of standards for diagnostics and therapy, and development of evidence-based guidelines. Achievements include establishment of central information, communication and management structures, creation of an AML intergroup comprising five study groups, formation of a myelodysplastic syndromes study group and establishment of platforms for diagnostics, genomics and proteomics, and medical informatics. Exchange of scientific progress is mediated by intra- and internet, bi-annual newsletters, regular project group meetings and annual network symposia. Already now, the network structures leukemia therapy and research in Germany and supports the spread of scientific excellence in the field of leukemias.

Acute Disease↗
PubMed2004

Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes.

Early plasmacytoid dendritic cell (pDC) leukemia/lymphoma has recently been described as a CD4(+)CD56(+) lineage negative malignancy with characteristic clinical, morphologic, immunophenotypic, and biological features. We present a case of a 72-year-old man who was diagnosed with isolated skin involvement 30 months ago and received numerous chemotherapy cycles that did not prevent three relapses of the disease, the last two involving the bone marrow. The bone marrow was nearly completely infiltrated with small- to medium-sized blasts displaying a high nuclear to cytoplasmic ratio, a cytoplasm with faint basophilia lacking granulations or Auer rods. Small vacuoles surrounding the nucleus were frequently observed. Flow cytometry showed CD4(+), CD56(+), CD45(+), CD38(+), HLA-DR(+), CD33(+), CD123(+), CD2(-), cyCD3(-), CD7(-), CD10(-), CD11b(-), CD13(-), CD14(-), CD16(-), CD19(-), cyCD22(-), CD24(-), CD34(-), CD57(-), CD61(-), CD64(-), CD65(-), cyCD79a(-), CD117(-), MPO(-), and TdT(-) population. At the second bone marrow relapse, CD117 was also positive. Our patient was initially treated with acute myeloid leukemia-type chemotherapy, later he was given acute lymphoblastic leukemia-type treatment, and at the last relapse he received CHOP chemotherapy. Each treatment led to rapid response of tumor manifestations with disease-free intervals of 7 months, 9 months, and 8 months, respectively. Although patients usually have an ominous prognosis, with only 25% living more than 24 months, our patient is alive after 30+ months and has again achieved complete remission after the last chemotherapy.

Aged↗
PubMed2004

[Clinical research in the "acute and chronic leukemias"competence network ].

Goal of the network is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among all major groups in Germany that deal with the leukemias in research and in patient care. In practice, cooperation between clinical groups and scientists in research institutes is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation and also increase information transfer from top research institutions to clinical translation. The network comprises more than 1400 participants in about 400 university centers, large community hospitals and specialty practices with functional communication structures, interdisciplinary cooperation and nation-wide logistics. The improved cooperation and the accelerated information transfer from the bench to the "bedside" results in an added value that ultimately results in improved survival results of patients and in superior competitiveness of involved research workers and clinicians. Sustainability is addressed by establishing a leukemia foundation to support long term financial coverage of the network and by negotiating a proposal for a European Network of Excellence against leukemia within the Sixth Framework Programme of the European Union.

Acute Disease↗
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31.

We analyzed data of 76 consecutive patients with myelodysplastic syndrome (MDS) and isolated del(5q) (n=66) or del(5q) plus one additional chromosomal abnormality (n=10) included in our MDS database over the last 26 years. The median age of our patient population was 66.8 years. The male to female ratio was 1:1.7. In all, 14 patients (18%) had advanced MDS with an increased medullary blast count. A total of 17 patients (22%) had significant dysplasia in the nonmegakaryocytic cell lines. Nearly half of the study population showed erythroid hypoplasia in the bone marrow. The projected median survival of patients with isolated del(5q) is 146 months for a median follow-up of 67 months. Patients with an increased medullary blast count and those with an additional chromosomal abnormality have a significantly shorter overall survival (24 and 45 months, respectively) than patients with isolated del(5q). We did not find survival differences for different cytogenetic breakpoints, nor did the amount of dysplasia have an impact on survival in our population. In total, 29 patients have died. Deaths occurred primarily due to transformation into acute leukemia, infection, or cardiac failure. Our data support the current definition of a separate entity of MDS with del(5q) that has been suggested by the World Health Organization.

Adult↗
PubMed2004

A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes.

Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+) months; five patients are in continuing response. In all, 23 patients suffered side effects > degrees II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.

Adult↗
PubMed2004

The 5q- syndrome.

The 5q- syndrome is a distinct hematological disorder with typical laboratory, morphological, cytogenetic, molecular, and prognostic features. It is defined as a myelodysplastic syndrome with a medullary blast count <5% and an isolated interstitial deletion of the long arm of chromosome 5, including bands q31-q33. The molecular basis of this disease has not yet been fully elucidated, but there is evidence that a commonly deleted region of 1.5 Mb harbors one or several tumor suppressor genes, the loss of which being the basic event leading to disease activity. The 5q- deletion has been demonstrated in very early hematopoietic precursors, including CD34+CD133+ and CD34+CD38-Thyl+ cells. Analysing data of 60 patients with the 5q- syndrome that were followed over a period of up to 28 years, we found a median age at diagnosis of 66.8 years and a female preponderance with a male to female ratio of 1:1.5. Anemia is usually macrocytic and combined with low reticulocyte counts and high erythropoetin levels. Three types of cytogenetic deletion are most prevalent: del(5)(q13q33), del(5)(q13q31) and del(5)(q22q33). The 5q- syndrome has a good prognosis with a median overall survival of 107 months at a median follow-up of 53 months, and a low probability of transformation to AML. An increase of the medullary blast count to > or =5% or the addition of one karyotypic anomaly severely reduces median overall survival. The most promising therapeutic approach is the novel thalidomide analogue CC5013 that is currently evaluated in an international phase II study.

Age Factors↗
PubMed2003

Fournier's gangrene.

Explore the source record for details and available documents.

Cord Blood Stem Cell Transplantation↗
PubMed2003

The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.

Acute Disease↗
PubMed2003

Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea.

The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.

Adolescent↗
PubMed2002

Evaluating the prognosis of patients with myelodysplastic syndromes.

One of the hallmarks of myelodysplastic syndromes (MDS) is their prognostic heterogeneity which complicates decision making regarding treatment for individual patients. The French-American-British (FAB) classification provides significant prognostic information, but carries the disadvantage of arbitrary demarcation of subgroups and overemphasis of morphological findings. In addition, there is considerable variation in survival and risk of acute myeloblastic leukemia (AML) development even within defined FAB subgroups, particularly in patients with refractory anemia with ring sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML). Over the last 2 decades, several research groups have tried to identify additional clinical, hematological, and cell biological parameters in order to more accurately predict the natural course of MDS. These investigations have clarified that the number and extent of peripheral blood cytopenias, the bone marrow blast count, and the cytogenetic pattern are the most powerful prognostic indicators in MDS. Recent efforts have been directed at constructing prognostic scoring systems. These scoring systems try to enhance the predictive power by combining several features of the disease, which have proved their independent prognostic weight on multivariate analysis. The International MDS Risk Analysis Workshop substantially advanced the prognostic categorization of MDS patients by proposing a new scoring system (International Prognosis Scoring System, IPSS) that can be successfully applied to risk assessment of newly diagnosed patients and will likely prove useful for the design and analysis of therapeutic trials in MDS.

Bone Marrow↗
PubMed2002

[Medicinal therapy of malignant lymphomas].

Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved.Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets. To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies.

Antineoplastic Combined Chemotherapy Protocols↗