[Reduplication behavior of chromosomes of group D (13-15) and identification of the extra-chromosome in trisomy D].
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Chromosomes↗
Biomedical subjects
T Büchner
Publications and source records attributed to T Büchner.
Treatment of refractory acute myeloid leukemia with mAMSA and VP 16-213 in combination: results of a clinical phase I/II study.
Twenty patients with refractory AML were treated with mAMSA and VP 16-213 in combination to assess the toxicity and anti-leukemic activity of the two-drug regimen. Refractoriness was defined according to the response to induction therapy consisting of 6-thioguanine, cytosine arabinoside and daunorubicin (TAD9) and the duration of the preceding remission. Patients were eligible for AMSA/VP 16-213 if they were primary non-responders against two TAD9 induction courses, had early relapses within the first six months, were nonresponders to one additional TAD9 course at later relapses or were at second or subsequent relapses. Therapy consisted of a five-day course of mAMSA 210 mg/m2/d on days 2, 3 and 4. VP 16-213 was applied on days 1 and 5 by a 1-h infusion of 100 mg/m2 followed by a 23 h infusion, the dosage of which was escalated in three steps from 110 mg/m2 over 200 mg/m2 to 230 mg/m2 in subsequent patients. Even at the highest dose of VP 16-213, toxicity was mild to moderate except for mucositis of grade III after two cycles and severe intrahepatic cholestasis in one case. Four of the 20 patients died within the first three weeks after the onset of treatment and were not evaluable for the assessment of antileukemic efficacy. From the remaining 16 patients five achieved partial remissions while no complete remission was obtained. Four of the five PR occurred in the eight patients with primary TAD9 resistance. These data indicate that AMSA/VP 16-213 reveals a moderate toxicity only, and that the combination may not be completely cross-resistant with TAD9. The overall anti-leukemic activity is limited however, and seems inferior compared to other presently available salvage regimens in refractory AML.
Adult↗
Subcutaneous low dose arabinosyl-cytosine and oral idarubicin in high risk adult acute myelogenous leukemia.
In order to further explore low dose chemotherapy for high risk acute myelogenous leukemia (AML), low dose Ara-C and oral idarubicin (LAI) were given to 33 patients of 24-84 (median 66) years with AML after myelodysplastic syndrome (MDS) (12 patients), refractory AML (13 patients), and AML with contraindications to intensive chemotherapy (8 patients). Patients received 1 to 4 cycles of Ara-C 10 mg/m2 q 12 h s.c. inject. on days 1-14 and idarubicin 20 mg/m2/d orally days 3, 4, 5. Three Three patients attained complete remission, four patients partial remission and one patient minor response, whereas 11 patients succumbed to early mortality from hemorrhage (two patients) and/or infections (10 patients). Three of 13 patients with heavily pretreated refractory AML went into remission compared to 3/12 with AML after MDS and 1/8 with AML and contraindications against intensive treatment. Median duration of CR is 102 (70-488 +) days. Thirty-two of 33 patients developed grade 4 hematological toxicity requiring platelet transfusions. The non-hematologic toxicity was acceptable. LAI provides a standardized therapeutic option especially for heavily pretreated patients with AML.
Administration, Oral↗
[Detection of aberrations in the karyotype of children with acute leukemia: a comparative analysis of cytogenetics and flow cytophotometry].
In the present study a comparative analysis of DNA flow cytometry and cytogenetics was performed in 257 children with acute leukemias to evaluate the comparability of both techniques for the detection of karyotype aberrations. DNA aneuploidies were detected in 88 (34%) patients while cytogenetic anomalies were revealed in 96 (37%) cases. From 76 patients (30%) with cytogenetically inevaluable metaphases 26 (35%) expressed aneuploid DNA stemlines. 67 (79%) of the 85 patients with normal karyotypes or normal modal chromosome numbers had a DNA index of 1.0 while DNA aneuploidies were identified in 18 cases (21%). 4 of 30 patients (13%) with pseudodiploid karyotypes revealed aneuploid DNA stemlines. While aberrations of the chromosome number by 1-3 chromosomes were combined with DNA aneuploidies in 9 of 35 cases (26%) only, all 31 patients with higher numeric chromosome changes also had aneuploid DNA stemlines. These data indicate that cytogenetics and DNA flow cytometry are complimentary methods for the detection of karyotype aberrations and should therefore be applied simultaneously.
Child↗
[DNA aneuploidy in children with acute leukemia: I. Incidence and clinical significance within the scope of the BFM studies].
Analyses of the cellular DNA content were carried out in 226 patients with acute lymphoblastic leukemia (ALL) and in 61 children with acute myeloid leukemia (AML) to assess the incidence and clinical significance of DNA aneuploidies. All children were treated within the BFM studies ALL 79/81 and 81/83 as well as AML 78 und 83. DNA aneuploidies were identified in ALL in 39,8% and in AML in 36,1% of cases. Within the ALL group a significantly higher rate of aneuploid DNA stemlines was observed for non-T/non-B ALL with 44,1% as compared to T-ALL with 14,3% (p less than 0,01). In AML the morphologic subgroups M 1/2 revealed a lower frequency of 21,7% DNA aneuploidies than M 4/5 leukemias with 44,4%. The rates of complete remissions were not different between patients with and without DNA aneuploidy neither in ALL nor in AML. In the study ALL 79/81, however, a tendency towards longer remissions for patients with DNA aneuploidy was found (p = 0.053) which could not be confirmed at present by the study ALL 81/83. In both ALL trials patients with the lowest pretherapeutic risk-score revealed the highest rate of aneuploid DNA stemlines.
Aneuploidy↗
[DNA aneuploidy in children with acute leukemia: II. Correlation with the phenotype of blasts, clinical picture and course of disease].
Analysis of the cellular DNA content was carried out in 162 children with ALL and 34 children with AML admitted to the university children's hospital Münster between 1979 and 1984. DNA aneuploidies were identified at a similar frequency in ALL (40%) and AML (44%). However, the degree of DNA aneuploidies (DNA-index) was significantly lower in aneuploid AML (median 1.09) than in aneuploid ALL (median 1.19). We found a significantly lower incidence of DNA-aneuploidies in T-ALL (3/21; 14%) as compared to non-T/non-B-ALL (60/137; 44%). No differences were found between children with and without DNA aneuploidy in PAS score and TdT activity. In non-T/non-B-ALL DNA aneuploidy is highly correlated with a long pretherapeutic history, with a low WBC and blast count and with a low serum LDH. Under the conditions of the ALL protocols BFM-79/81 and 81/83 no difference in the remission rate was found between the two patient groups. However, more relapses occurred so far within the group of children without DNS aneuploidy.
Acid Phosphatase↗
[Periprosthetic mineral density in cement-free hip replacement arthroplasty].
SUBJECT: We analysed the periprosthetic bone mineral density (BMD) in a prospective longitudinal study over two years after operation and in a separate cross-sectional study more than five years after implantation of cementless total hip arthroplasty (CLS-stem, Mecron threaded acetabular cup) by using dual-energy X-ray absorptiometry (DEXA). MATERIALS AND METHODS: In n = 53 patients (29 women, 24 men) we analysed the periprosthetic BMD prospectively in certain periods. All patients had an uncomplicated postoperative course and good clinical outcome (Merle d'Aubigne score > 12). In the cross-sectional study we analysed 23 patients (13 women, 10 men). Regions of Interest (ROI) were defined according to Gruen et al. for the periprosthetic femur and to De Lee and Charnley for the periprosthetic acetabulum. RESULTS: BMD significantly decreases in the periprosthetic femur as well as in the periprosthetic acetabulum during the first three months. In men BMD reaches its lowest values between six months (femur) and one year (acetabulum) after operation and then increases to 96.2% at the femur and 93.8% at the acetabulum. In women BMD decreases during the entire follow-up to 89.4% at the periprosthetic femur and 80.0% at the periprosthetic acetabulum. In the proximal zones 1 and 7 of the femur and the cranial-medial zone II of the acetabulum we observed the highest decrease of mineralisation. More than five years after implantation of the prosthesis BMD in the femur showed only little changes. On the other side BMD around the threaded acetabular cup significantly decreased to 67.4% in women and 79.1% in men. CONCLUSION: The results reflect the different stress on the periprosthetic bone after implantation of the prosthesis and fit to earlier reported good clinical results of the CLS-stem and to increased loosening rate of threaded acetabular cups after five years. Analysing changes of mineralisation in cementless total hip arthroplasty DEXA together with the analization scheme according to Gruen at the femur and to De Lee and Charnley at the acetabulum is a useful method and has been reliable in clinical practise.
Absorptiometry, Photon↗
Expression of the stem cell factor receptor C-KIT (CD117) in acute leukemias.
BACKGROUND AND OBJECTIVE: The receptor for stem cell factor (CD117) is the gene product of the c-kit proto-ontogene. Together with its ligand, the stem cell factor (SCF), it plays an important role in hematopoiesis. In this study, we review the cellular distribution of CD117 in normal hematopoiesis and in hematopoietic malignancies focusing on the differential expression in subtypes of acute leukemias. EVIDENCE AND INFORMATION SOURCES: This review is based on a literature search in the Medline database, personal publications and results obtained as a reference laboratory of the German AML-BFM, AMLCG and ALL multi-center therapy studies. STATE OF THE ART AND PERSPECTIVES: Membrane expression of CD117 can be found on leukemic blasts from approximately 60% of adult and childhood AML patients, often associated with an immature immunophenotype (CD34). Moreover, AML with t(8;21) are frequently CD117 positive. Despite earlier reports, most recent studies have not been able to demonstrate any significant prognostic impact of CD117 expression in either childhood or adult AML. A small proportion of T-lineage ALL (9%), mainly consisting of immature pro-T/pre-T-ALL, is CD117 positive. CD117 expression is rare in B-cell-precursor-ALL and occurs in less than 3% of cases. CD117 in combination with other antigens might facilitate the immunologic characterization of acute leukemias, especially those of myeloid and early T-cell origin.
Acute Disease↗