D. Söhngen
University of Düsseldorf
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Annals of Hematology | 1997
D. Söhngen; C. Specker; D. Bach; B. M. E. Kuntz; M. Burk; Carlo Aul; Guido Kobbe; Axel Heyll; K. A. Hollmig; W. Schneider
Abstract Antibodies against factor VIII occur in about 15–35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrands disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2–128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.
Lupus | 1997
Ch Specker; J. Rademacher; D. Söhngen; M. Sitzer; I. Janda; M. Siebler; H. Steinmetz; Matthias Schneider
CNS involvement is one of the hallmarks underlying poor prognosis in SLE and for therapeutic strategies it is difficult to assess which patients are at risk. As detectability of cerebral microembolic signals (MES) using long-term transcranial Doppler ultrasonography (TCD) proved to be predictive of past and future thromboembolic events in patients with carotid artery stenosis, we investigated whether MES might be similarly useful in patients with antiphospholipid syndrome (APS). Our study population consisted of 46 SLE patients and five with primary APS (pAPS). Twelve of the 46 patients with SLE, 10 of them with secondary APS (sAPS), and four of five patients with pAPS had a history of cerebrovascular ischaemia (CVI). MES in the middle cerebral artery were detected in 14 of 16 patients with and in one of 35 without CVI (P < 0.001). Antiphospholipid antibodies (aPL) were positive in 12 of 15 patients with and 18 of 36 without MES, and the rate of MES correlated to the titre of aPL. MES from APS patients resembled in their energy distribution those from patients with symptomatic carotid disease and were significantly different from those associated with artificial heart valves. In conclusion, cerebral MES are detectable in APS patients and correlate with a history of CVI. Whether this innovative method may provide individual risk assessment in APS patients has to be addressed in prospective studies.
Annals of Hematology | 1999
Guido Kobbe; D. Söhngen; U. Bauser; Peter Schneider; Ulrich Germing; K. P. Thiele; Claudia Rieth; Ali Hünerlitürkoglu; J. Fischer; M. Frick; Peter Wernet; Carlo Aul; Axel Heyll
Abstract We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5–50 μg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 μg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 μg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2–5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2×106 CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 μg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2×106 CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 μg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 μg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.
Journal of Hematotherapy & Stem Cell Research | 2002
Thomas Südhoff; D. Söhngen
The role of leukocyte-endothelial cell interactions during granulocyte colony-stimulating factor (G-CSF)-induced stem cell mobilization is unclear. To examine endothelial activation during this process, we determined levels of circulating endothelial adhesion molecules in healthy donors undergoing G-CSF-mobilized stem cell collection. Plasma levels of soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were serially determined by enzyme-linked immunosorbent assays in 10 healthy donors during G-CSF-stimulated stem cell mobilization. There was a significant increase in plasma levels of all three endothelial adhesion molecules (sE-selectin, p = 0.01; sICAM-1, p = 0.003; sVCAM-1, p = 0.0002) between day 1 and day 5 of G-CSF stimulation, but only sVCAM-1 concentrations exceeded the range obtained from unstimulated controls in all stem cell donors. Increases of sCAM were accompanied by increased numbers of white blood cells and CD34(+) progenitors in peripheral blood. G-CSF-stimulated peripheral blood progenitor cells (PBPC) mobilization results in increased levels of circulating endothelial adhesion molecules that were most evident for VCAM-1 molecules. Because soluble VCAM-1 remains active in binding to the VLA-4 receptor on CD34(+) cells, it may reduce stem cell adhesiveness to endothelial cells and to bone marrow microenvironment.
Acta Neurologica Scandinavica | 1999
J. Rademacher; D. Söhngen; C. Specker; I. Janda; M. Sitzer
Objectives – We investigated whether the detectability of microembolic Doppler signals (MES) in the intracranial circulation may help to define the individual cerebrovascular risk in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS). Material and methods – Retrospective cross‐sectional study of 70 patients with SLE with or without APS, and 30 controls with a history of cerebral ischemia of unknown cause. Of all patients, 38 had a clinical history of APS and 32 did not. Results – 15 patients with APS (39%) showed MES. In contrast, all patients without APS and 29 of 30 controls were microemboli‐negative. MES were more strongly associated with cerebrovascular symptoms than with APS, antiphospholipid antibodies, or cardiac pathology. The time elapsed since the last ischemic cerebrovascular symptom was significantly shorter in microemboli‐positive patients than in microemboli‐negative patients (P<0.001). Conclusion – MES may be related to disease activity in patients with SLE and APS. Their detection may help to assess individual cerebrovascular risk and contribute to therapeutic decision making and therapeutic monitoring.
Annals of Hematology | 1994
Axel Heyll; Carlo Aul; F. Gogolin; V. Runde; D. Söhngen; G. Meckenstock; H. H. Wolf; J. Zahner; M. Burk; M. Winkelmann; W. Schneider
SummaryConventional-dose Ara-C (200 mg/m2 d 1–5) combined with idarubicin (12 mg/m2 d 1–3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60–75) with AML according to the FAB criteria (M1n=3, M2n=10, M4n=6, M5n=2, M6n=2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.
European Journal of Haematology | 2009
Thomas Südhoff; M. Heins; D. Söhngen; Viola Lenz; Artur Wehmeier; G. Meckenstock; W. Schneider; Hans Reinauer; Axel Heyll; Carlo Aul
Abstract: Veno‐occlusive disease (VOD) of the liver is a frequent and life‐threatening complication of BMT. Recently, successful treatment by t‐PA has been reported but has been compromised by fatal bleeding events. Therefore, t‐PA application should be restricted to patients with severe VOD. However, moderate and severe forms of VOD are difficult to distinguish in early stages. We analyzed plasma levels of cross‐linked fibrin degradation products (D‐dimer) and soluble endothelial adhesion molecules such as sE‐selectin, sVCAM‐1 and sICAM‐1 in 10 consecutive patients undergoing allogeneic BMT to evaluate their use in identifying severe forms of VOD. During the observation period, 4 episodes of VOD occurred, 2 of which were fatal due to early onset of multiorgan failure. Concentrations of D‐dimer generally increased after transplantation. However, there was an additional significant increase in D‐dimer levels during severe VOD. Thus, D‐dimer levels above 1000 μg/1 were only found in 2 cases with severe VOD and fatal outcome. When compared with bilirubin concentrations substantial increases of D‐dimers appeared earlier during the course of severe VOD. In contrast, VOD episodes were not accompanied by significant increases in sE‐selectin, sVCAM‐1 and sICAM‐1 levels. It is concluded that measurement of D‐dimer concentrations may aid accuracy to the early diagnosis of severe VOD.
American Journal of Hematology | 1998
Guido Kobbe; Ullrich Bauser; Claudia Rieth; Ali Hünerlitürkoglu; D. Söhngen; M. Aivado; Carlo Aul; Axel Heyll
The therapeutic benefit of G‐CSF in the treatment of acute lymphoblastic leukemia has been well established. G‐CSF has been used to shorten neutropenia induced by conventional dose cytotoxic chemotherapy and allogeneic bone marrow transplantation. Recently autologous peripheral blood progenitor cell transplantation has been explored to treat high‐risk ALL. Several in vitro studies suggest that subpopulations of lymphoblasts express G‐CSF receptors. Furthermore, enhanced growth of Ph+ ALL cells expressing myeloid antigens stimulated by G‐CSF has been demonstrated in vitro. However, the clinical relevance of these findings has been questioned. We report a patient with my+Ph+ALL in whom the administration of G‐CSF after high‐dose Cytarabin and Mitoxantrone led to a significant mobilization of leukemic cells and contamination of the stem cell harvest during cytologic marrow remission. Am. J. Hematol. 58:330–333, 1998.
Leukemia Research | 1992
G. Meckenstock; C.H. Fonatsch; Axel Heyll; E.M. Schneider; G. Kögler; D. Söhngen; Carlo Aul; W. Schneider
Abstract Striking numerical and structural chromosome abnormalities (-Y, +8, i(7q), del(10)(q24), and del(11)(q21)) were detected by cytogenetic analysis in a patients bone marrow with morphological features of both acute lymphoblastic leukemia and myelodysplastic disorder. Surface marker analysis characterized blast cells to be CD2 − CD7 + CD3 − CD4 − CD8 − expressing γ/δ-T-cell receptor antigen and coexpressing CD11b and CD16. Exhibiting an identical phenotype as the leukemic cells, a prominent γ/δ-TCR + lymphocyte population was found in the bone marrow as well as in the peripheral blood. Cells of the latter compartment coexpressed CD56 and HLA-DR antigens and exhibited nonspecific cytotoxic activity. In the bone marrow cells NSCA could be induced after stimulation with interleukin 2 in vitro . Morphological, immunological, and cytogenetic findings suggest that γ/δ-T-ALL emerged from a myelodysplastic disorder after sequential steps of malignant transformation. Leukemic cells with “mixed lineage” character may provide evidence for a common progenitor cell in the bone marrow. Assuming that the leukemic cells represent the malignant counterpart of normal CD3 + γ/δ-TCR + cells the results may contribute to our understanding of the origin and differentiation as well as the possible steps of malignant transformation of a γ/δ-TCR + lymphocyte population.
Journal of Molecular Medicine | 1991
D. Söhngen; W. Schneider
Thrombocytopenia is the most common cause of bleeding tendency, and, if due to impaired platelet production, is best treated by platelet transfusions. Prophylactic transfusions for asymptomatic patients should be considered if platelet count is below 20,000/microliters. However, if bleeding occurs or surgery is inevitable, platelet count should be maintained above 50,000/microliters. The benefit of platelet transfusions has to be balanced against risks like fever, infections and haemolysis. The effectiveness of platelet transfusions should be examined after 1 and 24 hrs by measuring the corrected count increment (CCI). Not only alloimmunization is a reason for unsatisfactory platelet increments. A poor CCI can also be due to fever, sepsis, hepato-splenomegaly or special drugs, which must be taken into account when assessing the demand for platelet transfusions.SummaryThrombocytopenia is the most common cause of bleeding tendency, and, if due to impaired platelet production, is best treated by platelet transfusions. Prophylactic transfusions for asymptomatic patients should be considered if platelet count is below 20000/μl. However, if bleeding occurs or surgery is inevitable, platelet count should be maintained above 50000/μl. The benefit of platelet transfusions has to be balanced against risks like fever, infections and haemolysis.The effectiveness of platelet transfusions should be examined after 1 and 24 hrs by measuring the corrected count increment (CCI). Not only alloimmunization is a reason for unsatisfactory platelet increments. A poor CCI can also be due to fever, sepsis, hepato-splenomegaly or special drugs, which must be taken into account when assessing the demand for platelet transfusions.