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Biomedical subjects

D Hoelzer

Publications and source records attributed to D Hoelzer.

At least 325 records · Page 18Linked to original sources
PubMed1986

Age adapted induction and intensified consolidation therapy in acute myelogenous leukemia.

52 patients entered a study for remission induction and intensified consolidation in AML. Group I (age less than or equal to 50 years) received a combination of DNR, ara-C and VP16-213 for induction and early consolidation and HDara-C/DNR for late consolidation. Of 34 evaluable patients (25 first diagnosis, 9 first relapse), 27 achieved CR. 13 patients received 1-2 courses of HDara-C/DNR. Toxic symptoms of HDara-C/DNR were severe myelosuppression, infections, skin reactions, diarrhea and hepatotoxicity. CNS toxicity was not observed. 2 patients died from infection. The duration of granulocytopenia (less than 500/microliter) was 7-43 days (range) and of thrombocytopenia (less than 25,000/microliter) 5-34 days (range). Patients of group II (age greater than 50 years) received a modified regimen with reduced toxicity. Their number is too small for evaluation as yet.

Aclarubicin↗
PubMed1986

Treatment of AIDS-related Kaposi's sarcoma with recombinant gamma-interferon.

Four patients with the acquired immunodeficiency syndrome and Kaposi's sarcoma were treated with subcutaneous human recombinant gamma-interferon at a dosage of 200 micrograms = 2 X 10(6) U twice daily for at least 28 days. While the dosage of interferon was well tolerated, progressive disease was observed in all four patients studied. These results might be due to the selection of the patients presenting advanced stages (3 out of 4) with recurrent disease after previous chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Mixed megakaryocytic-granulocytic differentiation during diffusion chamber culture of peripheral blast cells from the blast crisis of chronic myelocytic leukemia.

Morphologically and cytochemically undifferentiated peripheral blast cells from three patients in blast crisis of Ph'-positive chronic myelocytic leukemia were analysed morphologically, immunologically and cytogenetically prior to and during in-vivo diffusion chamber culture (DC) to investigate their differentiation capacity. In two patients immunological markers characteristic of the megakaryocytic lineage were found on the original cells, but lineage-specific differentiation markers were absent on the blast cells of the third patient. During DC culture multilineage differentiation capacity could be demonstrated immunologically and morphologically in all three patients with expression of megakaryocytic and granulocytic markers as well as terminal differentiation along these lineages. Cytogenetic analysis prior to and during DC culture provided evidence that the cells differentiating in culture were derived from the blast crisis clones and that the event leading to blast crisis might have occurred in a pluripotent precursor cell which retained its differentiation capacity along several lineages.

Adult↗
PubMed1985

Megakaryocytic cells in mixed haemopoietic colonies (CFU-GEMM) from the peripheral blood of normal individuals.

The cellular composition of mixed haemopoietic colonies CFU-GEMM from the peripheral blood of normal individuals was investigated using both an improved in vitro culture assay and a monoclonal antibody reactive with the earliest megakaryocytic precursor cells. The frequency of CFU-GEMM was found to be 22 +/- 7/ml blood (mean +/- SE; n = 8) and 4.9 +/- 1.8/10(6) mononuclear cells. Double-labelling of single colonies with monoclonal antibodies against megakaryocytic as well as granulocytic cells revealed that only 18% of mixed colonies from the peripheral blood contained megakaryocytic cells as compared to 87% of mixed colonies from the bone marrow, while no difference existed with regard to granulocytic cells. It is concluded that circulating multilineage progenitor cells either require different culture conditions to express their megakaryocytic component or, alternatively, that the circulating pluripotent stem cell pool mainly consists of bipotent rather than multipotent progenitor cells.

Blood Cell Count↗
PubMed1985

Megakaryocytic differentiation capacity of human pluripotent bone marrow progenitor cells CFU-GEMM in vitro after cryopreservation.

The effect of cryopreservation on the pluripotent haemopoietic progenitors CFU-GEMM as well as on the megakaryocytic (CFU-Mk), erythroid (BFU-E) and granulocytic-monocytic (CFU-GM) progenitor cells was analyzed. Progenitor cell recovery after freezing, as determined in 5 experiments, averaged 89% for CFU-GEMM (range: 63% - 194%), 85% for CFU-Mk (range: 62% - 96%), 92% for BFU-E (range: 43% - 174%) and 60% for CFU-GM (range: 31% - 93%). Immunological analysis of individual mixed colonies using a double labelling immunoalkaline phosphatase slide technique and monoclonal antibodies against megakaryocytic and granulocytic cells revealed megakaryocytic cells in more than 79% (range: 73% - 94%) and 84% (range: 75% - 87%) of mixed colonies before and after freezing, respectively. Our results indicate that cryopreservation of human bone marrow cells does not alter the megakaryocytic differentiation capacity of the haemopoietic progenitor cells CFU-GEMM and CFU-Mk in vitro.

Bone Marrow Cells↗
PubMed1985

[Therapeutic results in acute myelogenous leukemia in the years from 1970 to 1982].

In a retrospective study, three groups of patients with acute myeloid leukaemia were analyzed in respect to the outcome of remission induction therapy: group I (vincristine, daunorubicin and prednisone) was treated between 1970 and 1976, group II (daunorubicin and cytosine-arabinoside) between 1976 and 1980 and group III (daunorubicin, cytosine-arabinoside, 6-thioguanine and consolidation therapy with cyclophosphamide, vincristine, cytosine-arabinoside and prednisone) between 1980 and 1982. Complete remissions were achieved in 49% (group I), 46% (group II) and 65% (group III) of the patients (p greater than 0.05, chi-square test). The mortality rate of the remission induction therapy was significantly reduced from 27% in group I to 15% and 13% in group II and III, respectively (p less than 0.05, chi-square test). The median remission duration increased significantly from four months (group I) to nine months (group III) (p less than 0.05, log-rank test). The long term results were about the same in the three groups. After three years, the proportion of patients being still in first remission was less than 10% in group I and II 13% in group III.

Adolescent↗
PubMed1984

Low-dose Ara-C in the treatment of acute leukemia. Cytotoxicity or differentiation induction?

The differentiation inducing effect of low-dose Ara-C on human myeloid leukemic cells was studied in two patients with subacute myelocytic and subacute myelomonocytic leukemia in vivo and in vitro. By continuous i.v. administration of 10 mg Ara-C/m2 over 12 h daily for 12 or 20 days complete remissions were obtained in both patients with normalization of the incidence of the committed progenitor cells BFU-E and CFU-C in the marrow while the incidence of pluripotent CFU-GEMM remained subnormal. Parallel cultures of the patients' bone marrow cells in diffusion chambers (DC) implanted in mice demonstrated a clear cytotoxic effect of low-dose Ara-C. The greater increase of granulopoietic cells within DC in the Ara-C exposed group than in control mice after the end of drug administration is, in addition, an indication for differentiation induction by this kind of Ara-C therapy.

Adult↗
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↗
PubMed1984

Growth kinetics of CFU-GEMM, BFU-E, and CFU-C in diffusion-chamber cultures of normal human bone marrow cells.

The proliferation and differentiation of human pluripotent hemopoietic precursor cells CFU-GEMM as well as of the committed precursors BFU-E and CFU-C within conventional diffusion chambers (DC) was studied. Low-density human bone marrow cells from eight normal donors were cultured in DC implanted into 750-rad-preirradiated mice. Cells harvested from DC after 1-14 days were assayed for the content of CFU-GEMM, BFU-E, and CFU-C. The mean number of progenitor cells inoculated per DC on day 0 was 59 (range 12-144) for CFU-GEMM, 367 (range 165-878) for BFU-E, and 632 (range 122-1168) for CFU-C. After an initial decrease in the number of all progenitors, an increase of CFU-GEMM was observed in five out of eight experiments and in the number of BFU-E and CFU-C in seven and five experiments, respectively. The assessment of the percentage of precursor cells sensitive to ara-C demonstrated a rise in the proportion of cells in S phase after implantation into DC consistent with reentry into active proliferation. From the observed behavior of the CFU-GEMM it is concluded that the earliest detectable human precursor cells do proliferate within DC.

Bone Marrow Cells↗
PubMed1983

Chronic myelocytic leukaemia: cytogenetical studies on haemopoietic colonies and diffusion chamber cultures.

In 20 patients with chronic myelocytic leukaemia in the chronic phase or in blast crisis, several in vitro (CFU-C, BFU-E) and in vivo (diffusion chamber) culture techniques were used to demonstrate the existence of a still diploid cell clone. In 4 out of 12 patients in the chronic phase, Ph1-negative metaphases were found in the various cultures for haemopoietic progenitor cells but not in the standard suspension cultures used for cytogenetics. However, all the 8 patients investigated during blast crisis had only Ph1-positive and other abnormal clones, indicating the loss of the diploid clone during progression of the disease.

Acute Disease↗
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

[Phase II study of AMSA in adults with acute therapy-refractory leukemias].

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.

Adolescent↗