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Biomedical subjects

W Pönisch

Publications and source records attributed to W Pönisch.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO).

PURPOSE: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). PATIENTS AND METHODS: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. RESULTS: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. CONCLUSION: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.

Adult↗
PubMed2006

[Late effects after chemotherapy].

Today, about 60% of adult patients and 80% children diagnosed with cancer will survive 5 years after diagnosis. Approximately two thirds of cancer survivors will experience at least one late effect, and about one third severe or life threatening late effects. The aim of cancer treatment today is to cure the malignant disease but at the same time, to minimize the incidence of post-treatment complications. In the current overview we summarize, based on the most recent publications, typical late effects in cancer survivors.

Adult↗
PubMed2004

Transmission of donor illness by stem cell transplantation: should screening be different in older donors?

With increasing donor age, the potential of transmitting diseases from donor to recipient reaches new dimensions. Potentially transmittable diseases from donors include infections, congenital disorders, and acquired illnesses like autoimmune diseases or malignancies of hematological or nonhematological origin. While established nonmalignant or malignant diseases might be easy to discover, early-stage hematological diseases like CML, light-chain multiple myelomas, aleukemic leukemias, occult myelodysplastic syndromes and other malignant and nonmalignant diseases might not be detectable by routine screening but only by invasive, new and/or expensive diagnostic tests. In the following article, we propose recommendations for donor work-up, taking into consideration the age of the donors. In contrast to blood transfusions, stem cells from donors with abnormal findings might still be acceptable for HCT, when no other options are available and life expectancy is limited. This issue is discussed in detail in relation to the available donor and stem cell source. Finally, the recommendations presented here aim at harmonized worldwide work-up for donors to insure high standard quality.

Age Factors↗
PubMed2003

Hematopoietic cell transplantation from related and unrelated donors after minimal conditioning as a curative treatment modality for severe paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days -4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day -3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH.

Adolescent↗
PubMed2002

Filgrastim mobilization and collection of allogeneic blood progenitor cells from adult family donors: first interim report of a prospective German multicenter study.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.

Adolescent↗
PubMed2001

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Adolescent↗
PubMed1999

[Pyoderma gangrenosum and portal vein thrombosis in a 33-year-old female patient].

HISTORY AND CLINICAL FINDINGS: The diagnosis of pyoderma gangraenosum (PG) was made in a 33-year-old woman with ulcerative (palm-sized) skin changes and pain of the lower leg that had developed over two weeks and was accompanied by fever (39 degrees C). Treatment with prednisolone and azathioprine was initiated. As soon as the medication was reduced new skin changes developed. Two months after onset of the illness she had to be hospitalized because of fever, epigastric pain on pressure and deteriorating general condition. Physical examination provided no significant further information. LABORATORY RESULTS: The differential count demonstrated leucocytosis (15.5 Gpt/l) with a marked monocytosis (25%) as well as anaemia (haemoglobin concentration 5.2 mmol/l). C-reactive protein was elevated (120.20 mg/l). Thromboplastin time was 60%, D-dimer 1000 micrograms/l, thrombin-antithrombin-III complex 9.7 micrograms/l. ADDITIONAL INVESTIGATIONS: Sonography and computed tomography of the upper abdomen revealed splenomegaly, ascites, thrombosis of the portal, splenic and superior mesenteric veins. Bone marrow puncture showed marked increase in blasts (14%) and monocytes (10%). TREATMENT AND COURSE: The findings indicated chronic myelomonocytic leukaemia with PG and the described venous thromboses. The cutaneous changes completely receded on administration of hydroxyurea (1.0 g/d). Other causes of the skin eruption were excluded. Phenprocoumon (INR between 2 and 3) was given in treatment of the thromboses. CONCLUSION: When PG is diagnosed, intensive search for an underlying cause must be undertaken, because of its frequent association with serious systemic disease. Only early specific treatment will improve the skin condition.

Adult↗
PubMed1998

Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure.

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.

Adult↗
PubMed1994

[Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

Autopsy↗
PubMed1991

[Immunohistologic investigations of paraffin-embedded lymph nodes after bone marrow transplantation in autopsy samples].

A histological and immunohistochemical analysis of paraffin-embedded lymph nodes from 31 autopsies after bone marrow transplantation (BMT) was performed (20 allogeneic, 10 autologous, 1 syngeneic). Monoclonal antibodies against CD 45RB, CD 20, CD 21, CD 35. CD 43, CD 45RO, CD 76 and Ki-B3, and antisera for detection of S 100-protein and immunoglobulin isotypes were used. None of the lymph nodes showed a regular reconstitution. The lymphoid cells, scattered in a diffuse pattern, were mainly CD 43-positive. Most of them also expressed the CD 45RO antigen. CD 20- and Ki-B3 positive lymphoid cells were nearly absent within the first 100 days after BMT. After that time B cell follicles were detectable in a few cases. Surprisingly, in nearly all cases with infectious complications, numerous plasma cells could be found. The origin of this plasma cells is discussed.

Antibodies, Monoclonal↗
PubMed1990

T-cell depletion and haematological side effects of two cytotoxic monoclonal antibodies.

We investigated two cytotoxic monoclonal antibodies of BL-series (BL-IIIB4 and BL-IIG2) according to T-lymphocyte depletion from bone marrow. Both antibodies work together with human complement similar Campath-1, which was tested parallelly. The extent of T-cell depletion is about 95% for all three antibodies. On the other hand the haemopoietic side effects tested by CFU-GM recovery and LTBMC are for the BL-antibodies not as strong as for Campath-1, especially in view of LTBMC. T-cell regeneration could be shown in long term cultures. Our results indicate a possible suitability of the two investigated antibodies for T-cell depletion of bone marrow.

Antibodies, Monoclonal↗
PubMed1989

[Results of therapy of 100 patients with acute leukemia--a retrospective unicenter 5-year analysis].

The results of therapy in 100 patients who newly fell ill (68 AML, 32 ALL) with acute leukaemia were evaluated (1981 to 1985). The 5-year-survival chance of all patients is 15% for AML, 18% for ALL, first of all it is depending on the degree of remission obtained. The CR rate is nearly 43% (AML) and 66% (ALL), respectively, shows a dependence upon age and is impaired above all by a high early death rate (supportive therapy). With increasing aggressiveness the results of the remission induction therapy improve, as it becomes clear in a comparison with an evaluation of patients 1965-1980 (CR: 15-32%). Also in the postremission therapy the results of intensive forms of therapy are more favourable: 4 years recurrence-free survival after CR in autologous bone marrow transplantation 50%, in allogenic bone marrow transplantation 40%, in cyclic chemotherapy 17%, in oral permanent therapy 0%. Starting from these findings the present conception of the therapy of acute leukaemias is discussed in connection with the literature.

Adolescent↗
PubMed1989

Allogeneic bone marrow transplantation for leukaemia and aplastic anaemia. Results of the Leipzig BMT Group.

In acute leukaemias there was a stable plateau in the survival curve at 45% after two years if grafted in first complete remission (n = 20) but only 13% of the patients are disease-free alive if grafted in a more advanced stage of the disease (n = 8). In 16 patients transplanted for chronic myeloid leukaemia the overall survival is 40%, in cases with graft-versus-host disease (GVHD) prevention by cyclosporine survival rate could be improved. Only 8 patients with severe aplastic anaemia, partially in low performance status were able to be transplanted; three died of infections, another by acute GVHD. The fatal complications in our study characterize the international well-known major problems in BMT: GVHD, interstitial pneumonitis, infections, graft failure in aplastic anaemia and recurrence of leukaemia, especially in more advanced leukaemia stage.

Anemia, Aplastic↗
PubMed1989

Immune recovery following bone marrow transplantation.

83 patients undergoing allogeneic or autologous BMT because of haematologic malignancies have been studied before and after transplantation at different intervals. The determinations consisted of lymphocyte counts, E-rosetting, lymphoblastic response, evaluation of serum immunoglobulin levels, skin testing, and in a smaller part of the patients surface marker studies using monoclonal antibodies of the BL-series. At first after BMT the lymphocyte and T cell counts went to normal between 4-18 weeks post transplant, about 4 weeks earlier in autologous than in allogeneic BMT. T suppressor cells showed an early increase compared to T helper cells which normalized much slower about 6 months after BMT. Lymphoblastic responses, however, tended to normal not before the second half of the first year both in autologous and allogeneic transplantation. Skin test reactivity became normal during the 2nd and 3rd year posttransplant, which was more complete in autologous than in allogeneic BMT. The IgG and IgM levels were depressed for half a year and IgA levels for 2 years. The most striking aspect was the multiphase course of lymphoblastic response in every individual patient. We suggest this to be the expression of sequential differentiation of donor lymphocytes.

Anemia, Aplastic↗
PubMed1989

Lethal complications in 30 patients after allogeneic BMT (BMT) and autografted (ABMT) patients (1980-1986) examined by autopsy.

Lethal and accompanying complications from 29 allogeneic, 8 autologous, and 1 syngeneic transplanted pts., died between 1980 and 1986 at the BMT-Center Leipzig were revisited. An important problem was that of systemic and local infections. We observed a predominance of bacterial and fungal infections within the first 3 weeks p.t., and later on a period of predominantly virus-associated infections. The most common early death (up to 3 months p.t.) was related to ICP, as a rule caused by CMV. GvHD was a common finding at autopsy, and GvHD of the bowel seems to facilitate infectious inflammations of the bowel. There was a positive correlation between severe GvHD and the occurrence of ICP. Neither of the died BMT pts. showed signs of relapse. After ABMT ICP did not occur. The lethal complications were septicaemia, local infections, relapse and haemorrhagic diathesis. A toxic effect of DMSO in 3 pts. must be taken into account. In conclusion, a rather small number of lethal factors indicates the steps in improving results of transplantation in the future.

Adolescent↗
PubMed1988

[Testing of acute myeloid leukemia of humans using monoclonal antibodies BL-DR, BL-M/G, BL-T2 and BL-Ig-L/1].

The leukemic blasts of 22 patients with acute myelocytic and myelomonocytic leukemia were tested by indirect immunofluorescence with the monoclonal antibodies BL-DR (directed against HLA-DR-antigens), BL-M/G (react with both granulocytes and monocytes), BL-T2 (pan-T-lymphocyte-antibody CD 5), and BL-Ig-L/1 (anti-light-chains-antibody). The leukemic blasts showed no crossreaction with BL-DR and BL-Ig-L/1. Both the antibodies BL-DR and BL-M/G reacted mainly with the acute myelomonocytic leukemias FAB M4 and only seldom with the acute myelocytic leukemias FAB M1, M2, and M3. The antibodies BL-DR and BL-M/G are able to confirm the diagnosis of acute myelomonocytic leukemia and to classify some previously unclassifiable leukemias.

Antibodies, Monoclonal↗
PubMed1988

[Use of monoclonal antibodies in the diagnosis of acute leukemia].

Immunological analysis has demonstrated the heterogeneity of acute lymphoblastic leukemia (ALL). The use of classical immunological methods and monoclonal antibodies against human lymphoid cell surface antigens have made it possible to subdivide ALL into five major subclasses: null ALL, common ALL, T-ALL, pre-B-ALL and B-ALL. We have studied in this report 8 cases of adult ALL diagnosed on morphological and cytochemical criteria. Some conventional markers and a panel of monoclonal antibodies have been used to analyse the differentiation of those patients' blast cells. In a second part we report two cases in which myeloid and lymphoid cell markers were observed simultaneously when 22 patients with acute myeloid leukemia were phenotyped according to the French-American-British (FAB) classification system.

Antibodies, Monoclonal↗