[Hormone therapy of metastatic breast carcinoma].
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Aminoglutethimide↗
Biomedical subjects
C G Schmidt
Publications and source records attributed to C G Schmidt.
Bone marrow transplantation for chronic granulocytic leukaemia.
Twenty-one patients with chronic granulocytic leukaemia underwent marrow transplantation. The donors were human-lymphocyte antigen-identical siblings in 19 cases. In the remaining 2 cases the donor was a parent in one and an identical twin in the other. The preparatory regimen included cyclophosphamide and 8.6 Gy total body irradiation given at either a dose of 0.1 Gy/min or 0.04 Gy/min. Five patients were in the accelerated phase of the disease, one was in remission following blast crisis, and the rest were all in the chronic phase. After chemotherapy and irradiation, all patients received bone marrow transplants. To date, nine patients are still alive, with a median survival of 64 days (range 28-683 days). One patient continued to have leukaemic cells and in another, the leukaemia recurred 18 months following transplantation. Interstitial pneumonitis was the cause of death of eight patients (38%). Graft-versus-host disease occurred in ten patients (47%).
Adolescent↗
[Chemotherapy of advanced lymphogranulomatosis. Results of MOPP/COPP treatment at the West German Tumor Center, Essen].
Between 1968 and 1979, a total of 271 patients with advanced Hodgkin's disease received as first systemic chemotherapy MOPP (mechlorethamine [nitrogen mustard], oncovin [vincristine], procarbazine and prednisone) or COPP (as above, but cyclophosphamide instead of nitrogen mustard). In 162 of the 271 patients (60%) full remission was achieved. Demonstration of systemic signs, bioptically confirmed bone-marrow infiltration and suboptimal cytostatic dosage correlated significantly with a lower full-remission rate. A significant trend towards a lower remission rate was demonstrated for stage IV disease, in patients with lymphocyte-poor or unclassified Hodgkin's disease and in those older than 30 years. A five-year recurrence-free period was achieved in 75.5% of patients: stage of the disease and bone-marrow infiltration had a clear influence on recurrence-free survival rate. The results show that 50% of patients with advanced Hodgkin's disease can be cured by chemotherapy.
Adult↗
Marrow transplantation for pancytopenia in dyskeratosis congenita.
A 33-year-old man with dyskeratosis congenita received a marrow transplant to treat severe pancytopenia. The graft was successful-, but the patient developed severe acute graft-versus-host-disease grade IV and died 51 days postgrafting. - The outcome of transplantation in dyskeratosis congenita is compared to that in Fanconi's anaemia due to the resemblance of both diseases in some aspects.
Adult↗
Ph-positive CML in a family with a constitutional Robertsonian translocation 14;15.
A patient with CML in chronic phase was admitted to our center for bone marrow transplantation. Cytogenetic analysis of bone marrow cells revealed a Ph chromosome due to a standard t(9;22) and a Robertsonian t(14;15). This Robertsonian translocation was also found in PHA-stimulated lymphocytes of the patient's sister, the donor of the bone marrow. A chromosome study of the whole family proved the constitutional character of the t(14;15) abnormality and showed that it was inherited from the father's side. All family members were phenotypically normal with normal mental status. Female carriers of the t(14;15), as well as wives of male carriers, had a high incidence of miscarriages and early death of their offspring. The occurrence of Ph-positive CML in a patient with a Robertsonian t(14;15) might indicate increased risk for the development of leukemia in patients with this constitutional chromosome abnormality. This assumption however, is limited by the rarity of the Robertsonian translocations.
Adult↗
Chemotherapy of metastatic seminoma.
Response to chemotherapy and survival was retrospectively analyzed in 28 patients with bulky retroperitoneal and disseminated seminoma treated between 1977 and 1983. The median age was 41 years (range: 23-52). All patients had histological evidence of pure testicular seminoma, however, 14 patients revealed moderate increases of human beta-chorionic gonadotropin levels. Prior radiotherapy had been given to 9/28 (32%) patients. Treatment consisted of at least four courses of simultaneous or sequentially alternating therapy with cisplatin, vinblastine, bleomycin plus/minus adriamycin (PVB +/- A), administration of ifosfamide or combination therapy with ifosfamide/cisplatin (IFS/DDP) or ifosfamide/etoposide (IFS/ETP). Twenty-five of 28 patients (89%) achieved a complete (CR), and 3/28 patients a partial remission. Relapse occurred in 1/8 CR patients after adjuvant postchemotherapeutic irradiation, and in 1/11 patients without any further radiotherapy. So far, 23/28 patients (82%) are free of disease after a median follow-up of 28+ (14+----82+) months. Marked myelosuppression was observed in previously irradiated patients, mainly after PVB +/- A therapy. In two patients, transient nephrotoxicity developed after PVB and IFS/DDP, respectively. After PVB +/- A chemotherapy, three patients revealed polyneuropathy, paralytic subileus and bleomycin-induced pneumonitis, respectively. In conclusion, the present series suggests a high probability of continuous CR in even bulky retroperitoneal and widespread metastatic seminoma. So far, no definite conclusions can be made on the therapeutic superiority of one of the different chemotherapeutic regimens used. However, this preliminary experience suggests that the combination of ifosfamide and etoposide or cisplatin may prove less toxic than sequentially alternating or simultaneous PVB +/- A chemotherapy.
Adult↗
[Complication-free pregnancy following bone marrow transplantation for severe aplastic anemia].
A bone marrow transplant had to be performed in a woman of 25 years of age because of severe aplastic anaemia. Immunosuppressive conditioning treatment consisted of 50 mg/kg cyclophosphamide given for four consecutive days. Regular menses reappeared already after four months. Pregnancy was confirmed after a year that resulted in giving birth to a healthy child in the 38th week of pregnancy via Caesarean section.
Adult↗
Late relapse of acute nonlymphoblastic leukaemia 6 years following allogeneic bone marrow transplantation.
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Adult↗
[High-dose cytarabine treatment in acute leukemias and leukemic meningiosis: clinical aspects and pharmacokinetics].
Clinical reports concerning the therapeutic effects of high dose Cytosine arabinoside (HD Ara-C) in meningeal leukemia are relatively rare. Pharmacokinetic studies, however, have indicated potentially effective concentrations of Ara-C in cerebrospinal fluid (CSF) during and after high-dose infusions of the drug given intravenously. In this report, the treatment results of HD Ara-C in 14 patients with refractory or relapsed acute leukemia are presented including those of 2 patients with meningeal leukemia. In these 2 patients as well as in 1 patient without central nervous system (CNS) leukemia, Ara-C and Ara-U concentrations in CSF and plasma were measured during a 6-day therapy with HD Ara-C (3 g/m2 q 12h 12 X). Ara-C and Ara-U levels were determined on Days 3 and 6 of therapy, each at the end of a 3-h i.v. infusion of the drug. In the 14 patients (8 with AML, 6 with ALL) treated, a total number of 17 treatment cycles were given for remission induction with doses of Ara-C ranging from 1-3 g/m2 q 12 h 6-12 X. A complete remission rate of 47% was achieved. The duration of remission ranged from 1 to 6 months. Of the 2 patients with CNS leukemia, 1 patient achieved complete remission both in CSF and in bone marrow, the other patient only in CSF. The mean concentration of Ara-C in CSF was 903 ng/ml with a ratio of 0.38 to that in plasma. Ara-C and Ara-U did not appear to accumulate in CSF or in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Treatment of hairy-cell leukemia with recombinant leukocyte A interferon.
A 29-year-old male patient with hairy-cell leukemia was referred for bone marrow transplantation. For tumor mass reduction a treatment with recombinant leucocyte A interferon was started. A complete remission could be achieved in the third month of treatment and no adverse side effects were observed. The patient refused bone marrow transplantation and a relapse was diagnosed 51 days after discontinuation of interferon therapy. Treatment of hairy-cell leukemia with recombinant leukocyte A interferon seems to be a promising approach.
Adult↗
Ferritin--a tumor marker in myeloid leukemia.
High serum ferritin levels without any correspondence to the amount of total body storage iron have been found in patients with leukemia. Investigating 96 adults with different types of leukemia, we found that serum ferritin can be used as a tumor marker in myeloid leukemias. Extremely high serum ferritin levels were seen in acute myeloblastic leukemia before treatment and in blastic crisis of chronic myeloid leukemia (ie, 21-fold increased serum ferritin concentrations). Patients with acute myeloblastic leukemia in complete remission had their ferritin concentrations decreased to normal. A relapse of the disease was paralleled by a repeated increase of serum ferritin level. In patients with chronic myeloid leukemia during the chronic phase we found normal serum ferritin concentrations, whereas blast crisis was associated with highly raised serum ferritin levels. We conclude that serum ferritin concentration must be valued as a clinically useful tumor marker in these types of leukemia, exhibiting a helpful and simple parameter in monitoring the activity of the disease.
Ferritins↗
[Effect of antineoplastic agents and ionizing radiation on a human testicular cancer heterograft].
Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease.
Animals↗
[Bone marrow transplantation in panmyelopathies and leukemias with special regard to gnotobiotic measures].
Bone-marrow transplantations were performed in 71 patients, 11 with panmyelopathy, 17 with recurrence of acute leukaemia, 25 with acute leukaemia and remission, 18 with chronic myeloid leukaemia. The transplantation was allogenic in 67, autologous in 2, isologous in 2. Eight patients each survived in the panmyelopathy and chronic myeloid leukaemia groups. In the group of patients with acute leukaemia only one patient of those in a recurrence survived the transplantation for several years, but after 6 years there was another recurrence. Of the 20 patients with acute myeloid leukaemia who received the transplantation during their first remission, 11 are still alive. Retransplantation because of the recurrence was employed in one case each of acute and chronic myeloid leukaemia. Main cause of death was interstitial pneumonia with an overall risk of 23%. Only 5% of patients developed severe acute graft-versus-host reaction, grades III-IV. The low incidence of this reaction is possibly due to the strict gnotobiotic measures which in most of the patients led to decontamination of the intestinal tract.
Adolescent↗
Vindesine/cisplatin chemotherapy in relapsed or primarily resistant small-cell carcinoma of the lung.
Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3-4 mg/m2) and cisplatin (60-100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the "less-than-complete-remission" group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.
Adult↗
[Biological effect of recombined leukocyte alpha-2-interferon in metastasizing colorectal cancers].
High-dosage recombinant alpha 2 interferon ( rIFN -alpha 2) was used for treatment of 12 patients with metastatic adenocarcinoma of the colon or rectum. In a prospective randomised fashion either 50 X 10(6) E/m2 as 30-minute infusion on 5 consecutive days four-weekly or 20 X 10(6) E/m2 subcutaneously thrice weekly were administered. No significant regression of the tumour could be observed. Treatment side-effects such as fever, shivering and fatigue were so pronounced particularly after subcutaneous administration that no patient could be treated for longer than 8 weeks. According to these findings single use of rIFN -alpha 2 does not seem to be of use for treatment of metastatic colorectal carcinomas. Subcutaneous administration is associated with considerable side-effects which subjectively in the majority of patients were considered intolerable.
Adenocarcinoma↗
Predictive tests in cancer chemotherapy. A reappraisal.
The evolution of medical oncology so far owes much to the preclinical and clinical development of antineoplastic agents. Prognostic factors and empiric treatment strategies have guided the clinician in his choice of drugs. In the light of increasing ethical restrictions met with phase I-II clinical trials and major advances in propagating human tumor cells outside the donor patient, a reappraisal of predictive tests in cancer chemotherapy is warranted. Among 'short-term assays' only the determination of steroid-hormone receptor content in tumor tissues has gained clinical acceptance, whereas other methods still suffer from theoretical or practical shortcomings. Both the human tumor stem cell assay and the xenograft model have revealed unique patterns of sensitivity for each individual tumor line. While interindividual heterogeneity among tumors sharing a common site of origin justifies efforts to develop predictive tests, microheterogeneity among tumor samples from the same donor patient limits the potential of this approach. Predictive tests should be performed in conjunction with clinical trials to ensure optimal extraction of information. As additional prognostic factors, they should in the near future accelerate drug development and reduce the hazard of unnecessary drug toxicity without therapeutic benefit.
Animals↗
SCE and cell cycle studies in leukemia.
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Bone Marrow↗
Macromolecular DNA-damage in murine and human leukemic and lymphoid cells after in vitro exposure to ASTA Z 7557 (INN mafosfamide).
Cyclophosphamide (CPA) is widely used against leukemic and lymphoproliferative diseases, but in vitro studies on response to this agent so far have been limited to instable derivatives with poor galenic properties. ASTA Z 7557 is a newly synthesized "activated cyclophosphamide" that circumvents the need for hepatic activation and has good stability. The critical cytotoxic lesions after exposure to bifunctional alkylating agents presumably are DNA interstrand crosslinks (ISC). We have, therefore, examined the formation and apparent removal of ISC after in vitro treatment with ASTA Z 7557 by use of the highly sensitive alkaline elution technique. Survival of murine L1210 cells was determined after 1 hour in vitro exposure with a D 37 value of 5.7 micrograms/ml (from the initial shoulder part of the survival curve) and a Do value of 1.5 micrograms/ml (from the exponential part of the curve). Previous labelling of L1210 cells by 125IUdR simplified the alkaline elution procedure but there was some cytotoxicity of the radiochemical itself with a reduction of cloning efficiency from 77% to 61%. The maximum of ISC was observed at 6 h after initiation of treatment with much of the damage apparently removed at 24 h. The simultaneous presence of DNA single strand breaks (SSB), however, confounds the analysis of DNA damage at 24 h and early cytolysis and unaided death of human lymphocytes often preclude the analysis of macromolecular damage at this time. Human peripheral blood cells isolated from patients with leukemic or lymphoproliferative diseases showed a remarkable heterogeneity with regard to the formation of ISC at 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗