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Biomedical subjects

T Büchner

Publications and source records attributed to T Büchner.

At least 181 records · Page 10Linked to original sources
PubMed1984

[Combined therapy with AMSA and etoposide (VP 16-213) in refractory acute myeloid leukemia. A phase I study].

In a phase I study the combination of AMSA and etoposide was applied to 12 patients with intensively pretreated, refractory AML to evaluate the basis for a subsequent phase II study in terms of drug dosage and timing. Each treatment cycle consisted in a 5-day regimen of AMSA 210 mg/m2/d days 2, 3 and 4. Etoposide was administered on days 1 and 5 with a constant loading dose of 100 mg/m2 by an 1-h infusion followed by a 23-h infusion, the dose of which was escalated in 3 steps from 110 mg/m2 to 200 mg/m2 and 230 mg/m2. In 18 treatment cycles the recommended dosage for a subsequent phase II study was found to be 660 mg/m2 etoposide per cycle together with 630 mg/m2 AMSA per course. Main side effects were nausea and vomiting as well as mucositis; 1 patient developed a severe intrahepatic cholestasis. In 11 from 16 evaluable treatment cycles a significant reduction of bone marrow blasts was observed with a mean cytoreduction rate of 0,26 log10/d. 4 patients, 3 of whom were primarily resistent to 2 TAD induction courses, achieved a partial remission.

Aminoacridines↗
PubMed1984

Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults.

One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c-ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

Acute Disease↗
PubMed1983

Immunotherapy in the treatment of acute myelogenous leukemia (AML): rationale, results and future prospects.

Patients with AML in complete remission (CR) are immunosuppressed; remission lymphocytes of at least a part of the patients are able to recognize autologous leukemic blasts; the CR represents a minimal residual disease. Thus, important conditions for a potentially successful active immunotherapy are given. Results of most earlier randomized trials on immunotherapy revealed some, but limited benefit with respect to survival. Encouraging effects, however, have been achieved by immunizing CR patients with high-dose neuraminidase-treated allogeneic blasts. Because these data have not been confirmed until now we recently initiated a randomized study utilizing identical treatment protocols. The preliminary results of the ongoing study still do not allow to draw any firm conclusions. Specific monoclonal antibodies or autologous cytotoxic T-cells may be useful tools for future immunotherapy of AML.

Animals↗
PubMed1983

[Recruiting patients and results of a preliminary study on the therapy of acute lymphatic leukemia and acute undifferentiated leukemia in adults].

The aim of the study was to improve remission quality through application of an intensified induction therapy successful in childhood ALL; in a modified form for patients of 15-35 years and in a reduced form for patients of greater than 35-65 years with ALL or AUL. The 8-week induction therapy consists of two phases. In phase I, prednisone, vincristine, daunorubicin, and L-asparaginase are given and in phase II, cyclophosphamide, cytosine-arabinoside, and 6-mercaptopurinee. As CNS-prophylaxis, intrathecal methotrexate, and CNS-irradiation with 24 Gy are used. After 3 months a re-induction therapy similar to the induction therapy is given with dexamethasone and adriamycin instead of prednisone and daunorubicin and without L-asparaginase. Maintenance therapy with 6-mercaptopurin and methotrexate follows over a period of 2 years. Since the formation of the study group in 1979 up to 30.06.81, 170 patients from 25 hospitals with newly diagnosed ALL or AUL were treated according to the protocol. Up to 30.11.81, 162 patients had completed treatment and were evaluable. Of these, 77.8% achieved complete remission, 80.7% in the age group 15-35 years and 68.3% in the age group greater than 35-65 years. The median survival time for all patients was 24 months and for the 126 patients with complete remission the median has not yet been reached (last observation 31 months). The median remission duration is 20 months. Prognostic factors for remission duration are (1) the number of chemotherapy courses required to reach complete remission, (2) the immunological subtype, (3) age and (4) initial leukocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

[The Münster study of intensive induction and consolidation therapy without maintenance therapy of acute myeloid leukemia. Results of 93 patients--cellular determinants for response and length of remission].

A 9-day high-dose 3-drug induction regimen including ARA-C, DNR, and TG at special time sequencing was given to 93 patients with AML, 15-74 (median 52) years old. After 1-2 courses for remission induction and, if possible, 2 identical courses of consolidation, no further therapy was applied during remission. Complete remission (CR) was achieved in 71% of all patients and in 74% of responders by 1 course only. Median remission duration is at 1 year with 13 patients in continuous CR for 13-38 (median 24) months. Patients completing consolidation reached a median remission duration of 22 months and those with rapid response to 1 induction course and with complete consolidation 38+ months. Patients monitoring included bone marrow DNA-histograms by flow cytometry, blood counts, percentage, and absolute number of blasts in bone marrow and LDH in serum. Among pretherapeutic parameters only LDH (inversely) correlated with CR duration. In contrast during early therapy rapid blast reduction, decrease of S-phase-index and of LDH as well as short recovery time of platelets and neutrophils predicted for low risk (when high risk included non-response and early relapse). Thus, monitoring of early cellular response parameters reflecting cellularity and proliferation seems to provide important individual determinants of therapeutic outcome.

Adolescent↗
PubMed1983

[Comparison of the therapeutic efficacity of 2 induction protocols in acute myeloid leukemia using exact quantification of bone marrow cellularity].

Using a recently developed technique for the determination of the pure bone marrow cell count per mm3 bone marrow, two different induction regimens for AML were compared for their efficacy, i.e. the therapy induced cytoreduction. In both protocols cytosine arabinoside, daunorubicin and 6-thioguanine were applied at comparable doses but different schedules. In both regimens a blast cell reduction of more than 2.0 log10 within the first 5 to 6 days of therapy strongly correlated (p less than 0.001) with the achievement of an adequate blast clearance in the marrow and complete remission (n = 18), while an inadequate blast cell reduction was revealed in all patients with a cell kill of less than 2.0 log10 (n = 9). Total cytoreduction on day 5 or 6 of therapy was comparable for both protocols. However, on one protocol a continuous logarithmic blast cell reduction was found while the cell kill followed a biphasic function on the other regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Cell kinetics in acute leukemia: a critical reevaluation based on new data.

The current study was undertaken to compare biopsy and aspiration sampling techniques for reliable cell kinetic analysis in acute leukemia and to reevaluate the clinical significance of cell kinetic data in this disease. Ad 1: One hundred forty-three paired simultaneously taken marrow aspirates and Jamshidi biopsies from 61 patients with acute nonlymphocytic leukemia (ANLL) were compared by means of flow cytometry (FCM) for cellular DNA and RNA measurements, autoradiography for 3H-TdR labeling index and liquid scintillation counting for 3H-TdR uptake. Aspirates were found unreliable for pretreatment evaluation and for monitoring of drug induced cell kinetic perturbations due to contamination with peripheral blood. Aspiration should, therefore, be replaced by marrow biopsy which provides reliable sampling of bone marrow for cell kinetic studies. Ad 2: FCM S-phase index determined from biopsy material was not found predictive for therapeutic response in 43 patients with ANLL treated with two different induction regimens. In one of the two protocols, changes in FCM S-phase index after 48 hours continuous infusion of cytosine arabinoside correlated significantly with clinical response and nonresponse, respectively.

Biopsy↗
PubMed1982

Bone marrow biopsy instead of 'marrow juice' for cell kinetic analysis. Comparison of bone marrow biopsy and aspiration material.

Since cell kinetic bone marrow studies have so far exclusively been carried out on aspiration material and have yielded inconsistent or even contradictory results, we investigated the adequacy and reliability of aspirates for cell kinetic analyses in comparison to biopsies. Paired samples of bone marrow (133) were taken simultaneously by aspiration and Jamshidi biopsy from 48 patients with acute leukemias and 67 patients with non-leukemic disorders. Cell kinetic analysis by (1) flow cytometry (FCM) of cellular DNA and RNA content, (2) autoradiography for [3H]TdR pulse labelling indices and (3) liquid scintillation counting of [3H]TdR uptake revealed significantly higher values in biopsies (p less than 0.001) exceeding the corresponding results from aspirates on average by factors of 1.65 for FCM S-phase index, 1.90 for G0/1 cells with high RNA content, 1.82 for [3H]TdR LI and 1.90 for [3H]TdR uptake. In more than 70% of all samples results from biopsies were 1.1-11.4 times higher, indicating that aspirates were equivalent to biopsies in fewer tan 30% of cases. Cell kinetic analysis in vitro blood/biopsy mixtures and measurements of DNA synthesis rate in corresponding aspirates and biopsies revealed that these discrepancies are due to the contamination of aspirates with non-proliferating nucleated blood cells. Biopsy, however, was found to provide representative and reproducible sampling of marrow for cell kinetic studies and should replace the presently used aspirate already characterized as "unreliable marrow juice" by Dameshek et al. in 1937 [18].

Acute Disease↗
PubMed1982

Multicentre study on intensified remission induction therapy for acute myeloid leukemia.

In a cooperative study at 13 centres in the Federal Republic of Germany, 213 adult patients with AML were treated for remission induction by a 9-day regimen consisting of cytosine arabinoside, daunorubicin and thioguanine (TAD) according to previously described sequencing. Complete remission was achieved in 70% of all patients. Complete remission rate was 57% in the 49 patients 60 years of age and older and 74% in the 164 patients under 60 years. Sixty-eight per cent of all complete remissions and 75% of those in the higher age group were induced by one induction course. Median survival was 10 months for all patients treated and 16 months for responders. Median remission duration was 13 months with 72 patients still in continuous remission for 1-31 months. Remission duration was not significantly different for patients treated either by monthly maintenance therapy or induction type consolidation without further therapy. However, patients completing two consolidation courses had a significantly longer remission duration of 22 months. Compared to similar multicentre studies on AML therapy the intensified induction regimen applied in this study shows an improvement even in older patients.

Adolescent↗
PubMed1982

Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia.

A new technique is introduced for determining the number of bone marrow cells per cubic millimeter marrow, providing an accurate and objective means for quantitating therapy-induced cytoreduction. The method requires a correction for admixed peripheral blood in bone marrow aspirates to measure the fraction of remaining pure marrow. While cell kinetic differences between blood, aspirates, and biopsies identify the proportion of contaminating blood cells, the ratio of red cell hematocrits in blood and aspirate gives the volume of trapped blood. By combining both procedures, bone marrow cell counts per unit volume pure marrow result (BMC/cu mm BM), which were found highly reproducible. Blast cell counts (BMBC/cu mm BM) were obtained by additional morphological differentiation. BMC and BMBC/cu mm BM were monitored in 16 patients with acute nonlymphoblastic leukemia treated with daunorubicin, cytosine arabinoside, and 6-thioguanine in combination and in 4 patients with end-stage acute leukemias and non-Hodgkin's lymphomas during high-dose thymidine therapy. Total and daily therapy-induced cytoreduction rates were significantly greater (P less than 0.01) in responders than nonresponders to either regimen. Changes in BMC/cu mm BM were also found representative for changes in BMBC/cu mm BM, since the majority of bone marrow cells were blasts. In acute leukemia. BMC/cu mm BM thus provides accurate and objective measurements of treatment efficacy in vivo and after short periods of drug exposure. Differences in cytoreduction rates within the group of responders also suggest possible prognostic implications.

Acute Disease↗
PubMed1981

Intensified remission induction therapy for acute nonlymphocytic leukemia (ANLL). Treatment report on 60 patients.

Sixty patients with ANLL were given intensified remission induction therapy consisting of thioguanine, cytosine arabinoside and daunorubicin (TAD). The mean age of patients was 47.6 years (range 18 to 74 years). Basing on leukemic cell kinetic data time sequencing of drugs was different from the original TAD protocol. Complete remission (CR) waa achieved in 43/60 patients (72%) with 10 CR in 15 patients over 60 years of age. Seventy-nine percent of the CR were induced by one cycle vs thirty percent reported from the original TAD regimen. The major cause of induction failure--in ten of the 60 patients--was thrombocytopenia refractory to platelet transfusions. Persisting leukemia after two induction cycles was documented in only two patients. Median remission duration by life table analysis is 10 months with 17 patients in continuous CR for 1+ to 22+ months.

Acute Disease↗
PubMed1978

[Peripheral microthrombotic purpura associated with acute promyelocytic leukemia in pregnancy. A light and electron microscopic study].

A case is presented of a pregnant patient in the 28th week of gestation with promyelocytic leukemia and an unusual thrombohemorrhagic skin lesion. Ultrastructural examination revealed a microthrombotic purpura. Reduced coagulation factors increased during heparin treatment. The exacerbation of disseminated intravascular coagulation is explained by a hypercoagulable state in pregnancy in association with the as yet unknown etiology of "promyelocytic fibrinopathic leukemia".

Adult↗