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Biomedical subjects

W Hiddemann

Publications and source records attributed to W Hiddemann.

At least 397 records · Page 22Linked to original sources
PubMed1987

Cytostatic effects in osteosarcomas as detected by flow cytometric DNA analysis after preoperative chemotherapy according to the COSS 80/82 protocol.

A total of 20 highly malignant osteosarcomas were studied by DNA flow cytometry after preoperative chemotherapy according to the COSS 80/82 protocol to assess their nuclear DNA content and the impact of chemotherapy on DNA ploidy and proliferation. Of the cases studied, 70% revealed aneuploid DNA stem lines with a median value of 1.67, and a median S-phase proportion of 16.1%. These data differed substantially from the results of a preceding study on untreated osteosarcomas revealing a higher frequency of DNA aneuploidy, higher DNA indices, and higher proportions of cells in S-phase. The pretreated tumors also showed a distinct relation between DNA content and the grade of tumor regression. No aneuploid DNA stem line was found in the responder group-I, whereas group-V (osteosarcomas with more than 50% viable tumor tissue) consisted almost completely of aneuploid DNA populations; all tumors with more than 2 DNA aneuploids were found in the latter group. All populations with a DNA index (DI) over 2.0 were found in the nonresponder groups IV and V, where all DNA aneuploids had an S-phase above 12%. No differences in DNA ploidy or proliferation were found in the various histological subtypes of pretreated osteosarcomas. These data indicate that flow cytometric DNA measurement in osteosarcoma may not only serve as a tumor marker, but also support the evaluation of morphologically established regression grades, thereby verifying the patient's prognosis: a high DI (over 2.0), a high number of DNA aneuploids (more than 2), and a high proliferation (S-phase above 12%) seemed to indicate a poor regression of the primary lesion, which may offer a pretherapeutic way of prognostic evaluation.

Adolescent↗
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↗
PubMed1987

Combined chemotherapy with m-amsacrine in high-risk patients with acute non-lymphocytic leukemia.

Thirteen patients (7 male, 9 female) aged 22-71 years (means = 55 years) with acute non-lymphocytic leukemia and contraindications for anthracyclin therapy were treated with combined chemotherapy using m-amsacrine primarily or in relapse. The main reasons for avoiding cardiotoxic substances were overt cardiac insufficiency and former administration of daunorubicin with more than 540 mg/m2 body surface area. Amsacrine was combined with 6-thioguanine, VP 16-213 and cytosine arabinoside in conventional or high dosage. Eight out of 13 patients (62%) achieved complete remission after one or two courses of chemotherapy. One patient showed partial remission and could be brought into complete remission with another chemotherapy using high-dose ara-C and mitoxantrone. Three patients died in aplasia after chemotherapy and 1 other patient had to be regarded as a complete non-responder. Remission duration and survival time for the 8 successfully-treated patients so far is 1-12 months; however, medians have not yet been reached, since only one of the eight patients relapsed after 6 months of complete remission. These data indicate a high efficacy of m-amsacrine in combined chemotherapy for acute non-lymphocytic leukemia in high-risk patients with contraindications for anthracyclins.

Acute Disease↗
PubMed1987

High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia.

In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy.

Adolescent↗
PubMed1987

High-dose cytosine arabinoside in combination with mitoxantrone for the treatment of refractory acute myeloid and lymphoblastic leukemia.

In the present study 55 patients with refractory acute myeloid leukemia (AML) (n = 44) and acute lymphoblastic leukemia (ALL) (n = 11) were treated with high-dose cytosine arabinoside (HD-ara-C) and mitoxantrone (HAM) to assess the toxicity and antileukemic activity of the two-drug combination. All patients had received a standardized first-line therapy according to the corresponding multicenter trials of the German AML and ALL cooperative groups and were considered refractory to conventional treatment. Therapy consisted of HD-ara-C 3 g/m2 every 12 hours on days 1 to 4; mitoxantrone was started at 12 mg/m2/d on days 3, 4, and 5 and was escalated to four and five doses of 10 mg/m2/d on days 2 to 5 and 2 to 6. From the 44 patients with AML, 24 (54%) achieved a complete remission, two a partial remission, and five were nonresponders. Thirteen patients died of infections (n = 11), pericardiac effusion, or acute cardiomyopathy. In refractory ALL, seven of 11 patients (64%) went into a complete remission, one patient was resistant, and three patients were early deaths. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. More severe CNS symptoms were encountered during five treatment courses. The median time to complete remission was 36 days. Excluding five patients who underwent bone marrow transplantations, the median remission duration was 4.5 months in AML and 2.3 months in ALL. The median survival time was three months for all patients and nine months for responders only. These data emphasize a high antileukemic activity of HAM in refractory AML and ALL and support the incorporation of the HAM regimen into first-line treatment.

Adolescent↗
PubMed1986

DNA stemline heterogeneity in colorectal cancer.

The current study was carried out on 88 colorectal carcinomas to assess the degree of intratumor heterogeneity as reflected by multiple aneuploid DNA stemlines and their relation to tumor stage and morphologic differentiation. Each tumor was segregated into an average of nine specimens (3-15), which were analyzed separately. DNA aneuploidies were identified in 72 cases (82%), 29 revealing multiple aneuploid DNA stemlines with up to four aneuploid subpopulations. In 10 of the 29 carcinomas with DNA stemline heterogeneity, a ratio of 2:1 was calculated from the different DNA indices, possibly indicating that the additional DNA stemline emerged from the first one by doubling its DNA content. No correlation was found between the overall frequency of DNA aneuploidies or heterogeneous DNA stemlines and the tumor stage according to Dukes' staging. Well-differentiated carcinomas tended to express aneuploid DNA stemlines more frequently than moderately or poorly differentiated tumors, although the morphologic intratumor heterogeneity did not correspond to the appearance of multiple aneuploid DNA stemlines. These data indicate a high degree of intraneoplastic diversity in colorectal cancer and emphasize the usefulness of DNA analyses for the quantitative assessment of tumor heterogeneity.

Aneuploidy↗
PubMed1986

DNA aneuploidies in adult patients with acute myeloid leukemia. Incidence and relation to patient characteristics and morphologic subtypes.

Analyses of the cellular DNA content were carried out by flow cytometry (FCM) in 148 adult patients with acute myeloid leukemia (AML) to assess the incidence of DNA aneuploidies and its relation to patient characteristics and morphologic subtypes. DNA aneuploidies were found in 54 of 131 patients with de novo AML (41.2%) and in 4 of 17 patients with AML after preleukemic syndromes. Subclassification according to morphology revealed the lowest rate of DNA aneuploidies in M1 leukemias (25%) and a significantly lower degree of DNA aneuploidy in M1 and M2 cases as compared to M4 and M5 subtypes (P less than 0.05). Within the group of M4 and M5 leukemias, patients less than or equal to 40 years of age had a higher frequency of aneuploid DNA stemlines (71.4%) than older patients (33.3%) (P less than 0.025). No differences between patients with and without DNA aneuploidy were identified for the initial leukocyte count, serum LDH, bone marrow S-phase index, bone marrow cell count/mm3 bone marrow nor the initial response to the induction regimen of 6-thioguanine, cytosine arabinoside, and daunorubicin (TAD). For remission duration a tendency towards a higher proportion of lung remissions was observed in patients with DNA aneuploidy.

Adolescent↗
PubMed1986

Frequency and clinical significance of DNA aneuploidy in acute leukemia.

Analyses of the cellular DNA content were carried out in 446 patients with newly diagnosed acute myeloid (AML) and lymphoblastic (ALL) leukemias in order to assess the frequency of DNA aneuploidies and its relation to immunologic and morphologic subtypes as well as its prognostic relevance. Based on high resolution FCM analyses and standardized reference measurements, DNA aneuploidies were identified at a similar frequency in children and adults with AML (38.0% and 40.0%) and ALL (40.0% and 37.4%). In AML aneuploid DNA stemlines were significantly less frequent in FAB-M 1 cases as compared to the other morphologic subtypes (p less than 0.05), whereas the degree of DNA aneuploidy was significantly lower in M 1 and M 2 leukemias as compared to the M 4 and M 5 subgroups (p less than 0.05). In ALL non-T/non-B and C-ALL revealed a higher frequency of DNA aneuploidies than T- and Null-ALL cases (p less than 0.05). No differences in the response to induction therapy were found between patients with and without DNA aneuploidy in children or adults with AML or ALL. In the childhood ALL trial BFM 79/81, however, a significantly higher frequency of long term remissions was observed in children with DNA aneuploidy (0.91 versus 0.66 at five years, p = 0.053). A similar though not significant tendency was also revealed from the AML studies BFM 78 in children and 78/81 in adults. In the subsequent studies these differences could not be confirmed at present, possibly because of the considerably shorter observation time.

Adult↗
PubMed1986

[Acute myeloid leukemia (AML) in adults. Further development of therapy based on clinical phase II and phase III studies].

By a review of relevant clinical studies on adult AML no substantial progress can be seen in the eighties so far. After the development of successful chemotherapy regimens during the seventies, further improvement can only be expected in small steps. Clinical studies, therefore, should concentrate on the analysis of the different components and new elements of treatment in order to utilize and combine them more effectively. For this purpose, a standardization of treatment and, for many aspects, a randomized comparison is inevitable. Thus, the role of monthly maintenance as well as of a special type of immunotherapy could be elucidated for the first time by our multicenter trial.

Adult↗
PubMed1986

High-dose cytosine-arabinoside and mitoxantrone in refractory acute myeloid leukemia: a clinical phase I/II-study.

In a multi-institutional study 26 patients with refractory acute myeloid leukemia were entered into a phase I/II study of HD-ara-C and mitox. HD-ara-C 3 g/m2 q 12h was given by 3h infusion on days 1-4. Mitox was started at 12 mg/m2/d on days 3, 4 and 5, and escalated to 4 and 5 doses of 10 mg/m2/d on days 2-5 and 2-6, respectively. From 24 patients presently evaluable for response, 12 achieved a CR and 2 a PR. 7 patients died of infectious complications within the first 4 weeks of treatment while persistent AML was found in 3 cases. Except for one death, possibly related to acute cardiomyopathy, toxicity was mild to moderate consisting of nausea and vomiting, mucositis and diarrhea. These data indicate a high anti-leukemic activity of HD-ara-C/mitox in AML refractory against conventional chemotherapy.

Anthraquinones↗
PubMed1985

Biological characterization of human bone tumors. VII. Detection of malignancy in a giant cell tumor of bone by flow cytometric DNA-analysis.

The biological behavior of giant cell tumors of bone often cannot be definitively evaluated by light and electron microscopical criteria. As DNA aneuploidy was found to be a highly sensitive marker of malignant cells, we have analyzed this descriptive parameter in 4 giant cell tumors of bone by flow cytometry. Three of the four cases were non-metastasizing giant cell tumors, the fourth was a clinically malignant neoplasm presenting extensive visceral metastases four years after first diagnosis. Neither light- nor electron microscopical findings provided unequivocal criteria for defining the biological dignity of the four tumors. DNA aneuploidies were identified in the metastasizing case only, whereas the three clinically benign tumors showed a unimodal euploid DNA distribution. Thus flow cytometric DNA analysis is an additional diagnostic tool for the detection of malignancy in giant cell tumors of bone.

Adult↗
PubMed1985

Thymus carcinoid.

A carcinoid of the thymus was studied by light- and electron-microscopy, immunohistology and flow-cytometry. The tumor showed a ribbon- and festoon-like growth-pattern with foci of necrosis, invasion of vessels and infiltration of mediastinal lymph nodes. The cytoplasma of the tumor-cells contained neuroendocrine granula and immunohistochemistry of ACTH was positive. The tumor-cells were connected by desmosomes, correlating to a pre-keratin positive immunohistology. In flow-cytometry the tumor-cells showed a near haploid DNA aneuploidy which is an extremely rare finding in solid tumors and in the few cases described indicative for treatment resistance.

Carcinoid Tumor↗