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T Büchner

Publications and source records attributed to T Büchner.

At least 145 records · Page 8Linked to original sources
PubMed1989

Accidental overdose of mitoxantrone in three patients.

Mitoxantrone is a new effective antineoplastic agent with activity against a wide range of tumors. Compared with the anthracycline drugs doxo- and daunorubicin, it exhibits a clearly lower toxicity and, most importantly, a reduced cardiotoxicity. The analysis of the side-effects recorded after accidental overdosage of the drug gives additional insight into its tolerability. Here we describe our observations in three patients who inadvertently received 100 mg m-2 (two pts) and 183 mg m-2 (one pt) as single slow bolus injections. The main side-effects were moderate nausea and vomiting, shaking chills, and profound but reversible neutro- and thrombocytopenia. There was no immediate cardiac toxicity. One patient with extensive previous daunomycin exposure developed congestive heart failure after 4 months. Two patients were not evaluable for late cardiac complications because of early death due to tumor progression.

Adult↗
PubMed1989

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia.

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

Adult↗
PubMed1988

[Clinical course and risk factors in patients with generalized mycoses].

A retrospective analysis of the clinical course of disseminated fungal infections in 32 patients revealed 25 cases of candidiasis, 5 patients with aspergillosis, and 2 with mixed fungal infections. All patients had undergone cytostatic therapy for malignant hematological diseases as the predisposing risk factor for fungal infection. 30 patients had severe granulocytopenia (less than 500/cmm). In addition, 30 patients had received broad spectrum antibiotics and 16 had been treated with corticosteroids. 17 of 32 patients were treated systemically with antimycotic drugs for proven fungal infection. No antimycotic agents were given to 15 patients because fungal infections were diagnosed only on post mortem examination. 19 patients succumbed to overwhelming disease, including 5 in spite of antimycotic therapy. Patients in whom systemic candidiasis was detected after recovery of granulocytopoeisis had a better prognosis than patients who developed systemic fungal infections during the period of ongoing severe granulocytopenia.

Adult↗
PubMed1988

High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application (S-HAM) indicating a high antileukemic activity in refractory acute leukemias.

In an attempt to further improve on the encouraging results achieved by high-dose cytosine arabinoside (HD AraC) and mitoxantrone (HAM) in refractory acute leukemias, a timely modified sequential schedule of both drugs was developed (S-HAM) and applied to 13 patients with far advanced acute leukemias, 8 of whom had been treated with the original HAM protocol before. Based on the cell kinetic and pharmacokinetic rationale outlined by Capizzi et al., HD AraC 3 g/m2 was applied every 12 h on days 1 and 2 followed by mitoxantrone 10 mg/m2/day on days 3 and 4. After 3 days without therapy the identical sequence was repeated on days 8 and 9 (HD AraC) and 10 and 11 (mitoxantrone), respectively. Of the 13 patients 9 (69%) achieved a complete remission, 2 were resistant and 2 were early deaths. Six of the 8 patients with prior HAM treatment obtained a further complete remission with S-HAM. In 2 of these patients a longer remission was induced by S-HAM than by the preceding original HAM treatment. Although these data are preliminary and need confirmation on larger numbers of patients, they strongly suggest a high antileukemic activity of the S-HAM protocol which may even be superior to the previously used HAM regimen.

Adolescent↗
PubMed1988

[Intensive combined therapy for high-risk ALL patients].

In the risk-adapted multicenter trial (02/84) for adult ALL the effectiveness of a consolidation therapy consisting of VM26 and Ara-C for high-risk patients was tested. Out of a total of 442 patients in the study, 79.2% achieved a complete remission. For the 182 high-risk patients the median remission duration is 17 months and the probability of being in continuous complete remission (CCR) is 34%. Improved results were found for elderly ALL patients between 35 and 65 years of age, whose median remission duration and CCR rate are 19 months and 40% respectively, compared to 15 months and 26% in the former study 01/81. The consolidation therapy has apparently also benefited patients with the immunological subtype c-ALL, for whom the CCR rate at 3 years is 53% in comparison to the previous value of 34%.

Adolescent↗
PubMed1988

Human recombinant granulocyte macrophage colony stimulating factor (GM-CSF) treatment of patients with acute leukemias in aplasia and at high risk of early death.

In the first clinical study on GM-CSF in acute leukemias continuous infusion of the growth factor is given to patients in aplasia and at high risk of early death due to age over 65 years and/or intensive chemotherapy for resistance or relapse. Among 6 patients (4 AML, 2 ALL) receiving a total of 7 courses two died too early to contributing adequate data. Three patients and 4 courses showed earlier neutrophil recovery than related control groups and a fourth patient with secondary AML showed a neutrophil recovery time in the normal range, but much shorter than her platelet and reticulocyte recovery. No evidence was obtained so far for leukemic regrowth in these patients including blood and bone marrow cytology, monitoring of DNA aneuploidy by flow cytometry and clonogenic cells by colony assays. Thus, GM-CSF may be useful for rescue after intensive chemotherapy of AML and ALL and may not necessarily increase the risk of leukemia progression.

Aged↗
PubMed1988

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗
PubMed1987

Tumor heterogeneity in osteosarcoma as identified by flow cytometry.

Measurements of the cellular DNA content by flow cytometry were carried out in 25 untreated osteosarcomas to identify the frequency of DNA aneuploidies and heterogeneous DNA stemlines in relation to histopathology. Analyzing multiple specimens from each single tumor (2-16; median, 4), highly malignant osteosarcomas were found to express DNA aneuploidies in 18 of 21 cases (86%) with multiple aneuploid DNA stemlines in 10 cases (48%). In three paraosteal osteosarcomas, no DNA aneuploidy was detected and a significantly lower proportion of cells in S-phase was observed as compared to the highly malignant osteosarcomas (mean 8.6% vs. 18.8%; P less than 0.05). Like in the paraosteal osteosarcomas, no DNA aneuploidy and a low fraction of cells in S-phase was found in the predominant cell population of one of the very rare sclerosing small cell osteosarcomas, which also revealed a second DNA stemline with a DNA index of 2.0. These results demonstrate a high degree of DNA stemline heterogeneity in highly malignant osteosarcomas. The data emphasize the usefulness of DNA measurements for the characterization of bone tumors and indicate the possibility of discriminating highly malignant from low-grade osteosarcomas.

Aneuploidy↗
PubMed1987

Postinduction and preremission chemotherapy alternatives for adult AML: three multicenter studies of the AML Cooperative Group.

Major chemotherapeutic alternatives for AML have been implemented and compared in three multicenter studies, including a total of 877 adult patients of all ages. The results strongly suggest that myelosuppressive postinduction treatment is a prerequisite for the achievement of long-term remissions. In addition, it was possible to establish an important antileukemic effect of monthly maintenance chemotherapy. Initial results from an intensive two-course preremission therapy concept revealed good practicability and acceptable toxicity, as well as promising response and remission durations by this new approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Neuraminidase-treated allogeneic blasts for maintenance in acute myelogenous leukemia: results of a prospective randomized trial.

Between July 1, 1981, and July 1, 1985, 167 patients with acute myelogeneous leukemia (AML) were treated with one or, if necessary, two courses of a modified TAD regimen (TAD9) for induction. 96 patients (58%) achieved a complete remission (CR); 62 achieved CR after one and 34 patients after two courses of TAD9. 29 patients (17%) were considered early deaths, and 42 patients (25%) nonresponders. For CR maintenance 64 patients were eligible according to protocol criteria; 33 patients were randomized to chemotherapy, only, (CT) by monthly courses of cytosine arabinoside (ARA-C) alternatingly combined with daunorubicin or thioguanine or cyclophosphamide, while 31 patients were randomized to receive immunotherapy in addition to chemotherapy (CIT) by intradermal injections of 10(10) neuraminidase-treated viable allogeneic blasts per immunization interspersed between the CT courses. Maintenance therapy was given for up to 3 years. The median survival in CT patients is 23 months, while in CIT patients the median has not been reached after 54 months; corresponding median relapse-free survival is 15 months for the CT patients as opposed to 40 months for the CIT group. The differences are not significant. Comparing CT with CIT, the survival data show a persistent trend in favor of CIT; under the conditions of the study, however, a substantial benefit of immunotherapy may be restricted to a certain subset of patients with low risk for early relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

High-dose cytosine arabinoside and mitoxantrone (HAM) for the treatment of refractory acute lymphoblastic leukemia.

In a clinical phase-II study 11 patients with refractory ALL were treated with high-dose AraC and mitoxantrone in combination (HAM). Refractoriness was defined as: 1. primary resistance against the BMFT induction protocol; 2. first relapse with non-response to the B-ALL/NHL regimen as salvage treatment; 3. second and subsequent relapses. Therapy consisted of HD-AraC 3 g/m2 every 12 h by a 3-h infusion on days 1-4 and mitoxantrone 10 mg/m2/d on days 2-6. Seven of the 11 patients achieved a complete remission, 1 patient was refractory against 2 HAM cycles and 3 patients died during bone marrow aplasia. Toxicity was acceptable, consisting mainly of nausea and vomiting, mucositis and diarrhea. One patient who had completed the prophylactic CNS treatment with intrathecal MTX and cranial irradiation immediately before entering the HAM protocol developed severe signs of cerebral toxicity. These data indicate a significant activity of HAM in refractory ALL and suggest that the combination should be applied at earlier stages of ALL treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Alternatives and further development of therapy of acute myeloid leukemia in adults. Update of West German multicenter studies].

The 1982 randomized, multicenter trial on adult-AML in West Germany revealed a superiority of remission duration (p = 0.004) and survival (p = 0.06) for patients receiving monthly myelosuppressive maintenance chemotherapy after TAD9-induction and consolidation as compared to patients without maintenance. In the 1985 pilot study double induction as a new approach followed by consolidation and monthly maintenance in patients up to 60 years of age was found well practicable, with 77% complete remissions and 12% early deaths in 81 patients. In addition preliminary remission duration and survival at 1 1/2 years appear favorable.

Adolescent↗