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Biomedical subjects

W Wilmanns

Publications and source records attributed to W Wilmanns.

At least 127 records · Page 7Linked to original sources

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.

Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.

Adult↗

Enhanced endogenous leukotriene biosynthesis in patients treated with granulocyte-macrophage colony-stimulating factor.

The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is being used in clinical trials for its potential in the treatment of hematopoietic insufficiency due to various causes. Involvement of leukotrienes in the effects of GM-CSF is suggested by analytical and pharmacologic evidence obtained in vitro. However, until now no data in support of a role of leukotrienes in GM-CSF action in vivo have been presented. In the present investigation this question was approached by measurement of endogenous cysteinyl leukotriene formation in patients treated with the cytokine for cytopenia induced by cytostatic drugs or for refractory anemia with excess of blasts (RAEB). Endogenous cysteinyl leukotriene formation was assessed by determination of urinary leukotriene metabolites using combined high-performance liquid chromatography and radioimmunoassay analysis. After GM-CSF administration a distinct increase in urinary cysteinyl leukotrienes was found in the cytopenic and the RAEB patients that ranged from 2.3- to 57-fold and 2.4- to 333-fold, respectively. In the cytopenic patients the increase in leukotriene production was correlated to an expansion of peripheral blood leukocytes; RAEB patients responded to GM-CSF with enhanced leukotriene biosynthesis even if the peripheral leukocytes decreased, possibly due to an abnormal number and/or irritability of leukotriene-producing cells. The increase in endogenous leukotriene production during therapy with GM-CSF may indicate that leukotrienes play a role in GM-CSF action in vivo.

Adolescent↗

Cytogenetic and molecular analysis of a "masked" Philadelphia chromosome in chronic and blastic phases of chronic myeloid leukemia.

A "masked" Philadelphia chromosome (Ph), t(1;22;9)(p32;q11;q34), was found in the bone marrow and peripheral blood cells of a patient with chronic myeloid leukemia (CML) during the chronic and blastic phases of the disease. As an additional change, a reciprocal translocation t(12;13)(p13;q14) was observed in the blastic phase. Southern blot analysis showed a rearrangement of the breakpoint cluster region (bcr). Northern blot analysis with a c-abl probe showed an abnormal 8.5 kb c-abl RNA transcript in addition to the normal 6- and 7-kilobase (kb) c-abl species. Thus, the results demonstrate the presence of a c-abl/bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t(9;22)(q34;q11) of CML.

Blast Crisis↗

Possibility to improve preservation of whole blood by leukocyte-depletion before storage.

In order to evaluate the influence of leukocytes in whole blood on the standard blood bank conditions for storage, we compared several parameters of red cells, leukocytes and platelets in leukocyte-rich and leukocyte-poor whole blood over a storage period of 5 weeks. The leukocyte-depleted units were prepared by filtration with a leukocyte trapping filter (Sepacell R500A). Our data indicate improved storage conditions, made evident by significantly lower cell damage: smaller increases of elastase, beta-thromboglobulin and lactate dehydrogenase in leukocyte-depleted blood. This improvement was achieved in a simple two-bag system using only filtration, without addition of rejuvenating solutions. In addition, this procedure allows greater flexibility in the use of filtrated blood for transfusions.

Adenosine Triphosphate↗

Clinical, biochemical and cytokinetic parameters for distinguishing smouldering and rapidly proliferating variants of acute leukaemia.

In a retrospective study, 10 patients with smouldering leukaemia (SML) were examined between 1982 and 1987. These patients typically showed the morphological criteria of acute myelogenous leukaemia (greater than 30% blasts in the bone marrow) in most cases together with a long survival time (median 16 months; 5 patients more than 22 months; 5 patients between 2.3 and 6.3 months) without the use of aggressive chemotherapy. At initial diagnosis the blast cell populations of patients with SML were characterized by significantly reduced cytosolic thymidine kinase activity (TK), thymidine-incorporation (dTR) and deoxyuridine incorporation (dUR) into DNA as well as reduced amounts of DNA-synthesizing S-phase-cells (%S) in the bone marrow (BM), compared to those patients with a rapidly proliferating acute myelogenous leukaemia (AML) and to healthy individuals. None of the SML-patients showed clinical symptoms such as night-sweat, weight-loss, hepato- and splenomegaly or lymphadenopathy at initial diagnosis. For characterization of SML vs AML we recommend the use of the biochemical parameter TK activity and the observed absence of the above-mentioned clinical symptoms. The transition to the rapidly proliferating type of AML can be recognized by an increase in the values of the biochemical and cytokinetic parameters. The blast count in the bone marrow is not suitable as a diagnostic criterion for the definition of SML vs AML or its transition to the rapidly proliferating type of AML.

Adolescent↗

Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study.

From July 1986 to July 1989, 40 patients (92% pretreated) with deep-seated, advanced soft tissue sarcomas (STS, 25 patients), Ewing's sarcomas (ES, eight patients), osteosarcomas (OS, three patients) and chondrosarcomas (ChS, four patients) were treated at the University of Munich in a protocol involving regional hyperthermia (RHT) combined with ifosfamide plus etoposide. A total of 265 RHT treatments (mean, 6.6 RHT per patient) were applied including 33 pelvic, four extremity, and three abdominal sites. The mean tumor volume was 537 cc (range, 50 to 2,980 cc). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1 to 5), etoposide (100 mg/m2, days 1, 3, and 5), and mesna (300 mg/m2 x 4, days 1 to 5) with RHT given only on days 1 and 5 in repeated cycles every 4 weeks. Acute toxicity consisted primarily of pain (57%) combined with local discomfort within the annular phased array applicator (AA) of the BSD hyperthermia system (BSD Medical Corp, Salt Lake City, UT). The average maximum systemic temperature was 37.4 +/- 0.5 degrees C, and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. Detailed thermal mapping by invasive thermometry was performed in all patients. In 38 assessable patients, the overall objective response rate was 37%: six complete responses (CRs), four partial responses (PRs), and four favorable histologic responses (FHRs) (95% confidence limits, 22% to 54%). Complete responders are alive and disease-free at 40, 35, 23, 19, 19, and 8 months. Of patients with PR and FHR, two died from metastatic disease after 4 and 17 months and one died from other disease after 27 months. The remaining five patients are stable at 37, 25, 21, 13, and 8 months. Eleven patients showed no change (NC), and 13 patients showed local tumor progression (PD). The mean observation time for all patients was 11.6 months. The time-averaged temperatures (Ts) of all RHT treatments calculated as 20% (T20), 50% (T50), or 90% (T90) of measured tumor sites differed significantly between responders and nonresponders (T20, P = .003; T50, P = .006; and T90, P = .004; respectively). These data support activity for ifosfamide-etoposide combined with RHT in pretreated patients with advanced sarcomas.

Adolescent↗

[Normal immune function in centroblastic-centrocytic and centroblastic lymphoma].

We tested in vitro lymphocyte reactivity using 5 mitogens and 9 antigens, measured lymphocyte and lymphocyte subpopulation counts, granulocyte chemotaxis and adherence in 10 patients with centroblastic-centrocytic lymphoma (CB-CC), 7 patients with centroblastoma (CB) and 88 healthy controls. The control group could be divided into 3 clusters with significantly different lymphocyte reactivity by means of cluster and discrimination analysis (BMDP2N): 21 high-, 18 medium- and 49 low responders. Comparing lymphocyte reactivity of CB-CC and CB patients to each of the 3 immunofunctional different control groups yielded the surprising result that both malignant lymphomas are equivalent to the low responding control group and show a low, but still normal in vitro immune function.

Adult↗

[Normal immune function in highly malignant non-Hodgkin's lymphomas].

We performed lymphocyte transformation tests using 14 different mitogens and antigens, determined T-cell- and T-cell subpopulation counts (CD3, CD4, CD8), the CD4/8 ratio, granulocyte chemotaxis and granulocyte adherence in 88 healthy controls, 8 patients with immunoblastoma (IB) and 6 patients with lymphoblastoma (LB). Using cluster and discrimination analyses (F-test; t-test) according to the programs of the UCLA (BMDP2N) the control group (n = 88) could be divided into 3 groups with significantly different lymphocyte responses to mitogenic and antigenic stimulation (21 high-, 18 medium, and 49 low responders). Comparing the lymphocyte reactivity of IB and LB patients to these immunofunctional different clusters we found a complete accordance of the lymphoma patients to the healthy low responder group.

Adult↗

Chemotherapy of invasive thymoma. A retrospective study of 22 cases.

The authors report on combination chemotherapy in 22 patients (seven men, 15 women; age 20-67, median 38.5 years) with incompletely resected invasive thymoma. Twelve of 22 patients have had prior radiotherapy of the tumor (four of 12 local failure, eight of 12 remote metastases). By subsequent chemotherapy five of 12 obtained complete remission (CR). One of them died by relapsed tumor, another by an intercurrent infection. At 5 years after diagnosis the survival rate of the 12/22 patients was 33% (Kaplan-Meier). Ten of 22 patients received chemotherapy as primary treatment of incompletely resected thymoma. Four of 10 obtained CR. One of them was lost during follow-up, the others received adjuvant irradiation of the mediastinum and are free of disease. Two of ten obtained partial remission (PR), but relapsed within 6 months after chemotherapy. At 3 years after diagnosis the survival rate of the 10/22 patients was 34%. Thirteen of 22 patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP/bleomycin as first chemotherapeutic regimen. Five of them achieved CR. Cyclophosphamide, vincristine, and prednisone (COP) or COP plus procarbazine (COPP) was administered to six of 22. Three of them obtained a CR and one a PR. In an alternating manner COPP and Einhorn regimens were given to two of 22, one of which had a CR. In one of 22 the doxorubicin, bleomycin, cisplatin, prednisone (BAPP) regimen was followed by a PR. The authors conclude that combination chemotherapy is effective in the first-line postsurgical treatment of incompletely resected thymoma and also in the treatment of local or metastatic relapses after radiotherapy.

Adult↗