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Biomedical subjects

R Becher

Publications and source records attributed to R Becher.

At least 127 records · Page 7Linked to original sources

Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia.

A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.

Adult↗

Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia.

In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.

Acute Disease↗

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↗

Chromosome changes in a secondary lymphoma.

A case of probable secondary lymphoma, poorly differentiated lymphocytic lymphoma (PDLL), is described in which two chromosomal translocations were observed, i.e., t(10;19)(q11;q13) and t(1;6)(q21;p11.1-2). A consistent numerical aberration was monosomy of chromosome #21. Accumulation of more data on secondary lymphomas is necessary in order to reach a general conclusion as to whether or not there are any nonrandom chromosomal aberrations that differentiate primary from secondary lymphomas.

Adenocarcinoma↗

[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↗

Combination chemotherapy (VAC/FMC) with immunostimulation in metastatic breast cancer: a randomized study comparing different times and routes of administration of Corynebacterium parvum.

From January 1978 to December 1980, 222 patients with metastatic breast cancer were included into a prospective multicenter trial. All patients were treated once a month with six cycles of VAC- (vincristine, adriamycin, cyclophosphamide) chemotherapy, followed by FMC (5-fluorouracil, methotrexate, cyclophosphamide) until progression was documented. By random assignment, the patients received immunostimulation with Corynebacterium parvum (CP) by one of four methods: subcutaneous (SC) on either day 1 or day 14, intravenous (IV) on either day 1 or day 14. The 214 evaluable patients were equally distributed to the four arms. The rates of complete or partial response to VAC/FMC plus CP did not differ significantly between the treatment groups. Of our patients, 22-33% were definite treatment failures. The Kaplan-Meier curves of duration of remission (medians 14 vs. 9 vs. 13 vs. 11 months) did not differ significantly. Only small differences in survival were noted among the four study groups (medians 15.4 vs. 17.5 vs. 17.2 vs. 13.0 months). However, complete and partial responders lived significantly longer (Log rank test P = 0.008), when CP was given on day 14 by the SC rather than IV route (29+ vs. 14.3 months). Patients in the four study groups were treated with virtually identical doses of VAC/FMC chemotherapy. Patients receiving CP intravenously on day 14 experienced significantly lower mean leukocyte counts than patients in the other groups. Many patients suffered from high temperature (requiring treatment with antipyretics) and severe gastrointestinal toxicity, particularly when CP was given IV on day 1 together with the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Clonal evolution with isodicentric Ph1 chromosome in Ph1-positive CML: karyotypic conversion after bone marrow transplantation.

Clonal chromosomal evolution was observed in a 16-year-old boy suffering from Ph1-positive CML. An isodicentric Ph1 chromosome appeared 20 weeks after the initial diagnosis. At that time an allogeneic bone marrow transplantation was performed. Thereafter, during an observation period of more than 13 months, chromosome analyses showed neither the Ph1 chromosome nor the abnormal isodicentric variant. Close cytogenetic monitoring is suggested to reveal early unfavorable prognostic signs of the onset of blast crisis before it becomes evident in the bone marrow morphology.

Adolescent↗

A high-resolution study of chromosome changes in a human prostatic carcinoma cell line (LNCaP).

A high-resolution study of chromosomal rearrangements in a human prostatic cancer cell line, LNCaP, has been performed. The cytogenetic analysis revealed a pseudodiploid karyotype and the presence of seven marker chromosomes resulting from five aberrational events. The analysis of four clones derived from the original line showed a near-tetraploid chromosome number and the presence of the same seven markers observed in the original line. This is the first complete description of karyotypic rearrangements in a prostatic cancer cell line.

Cell Line↗

Sister chromatid exchange in normal and Ph1-positive leukemic cells after mitomycin-C treatment in vitro.

The sister chromatid exchange (SCE) frequency was investigated in normal bone marrow and Ph1-positive cells of chronic myelocytic leukemia (CML) patients with and without mitomycin-C (MMC) treatment in vitro. Even though the spontaneous SCE frequency was found to be significantly lower in CML cells, the absolute SCE values after MMC treatment did not differ between leukemic and normal cells, and this seems to indicate an equilization of SCE rates. However, the fact that leukemic cells with lower spontaneous SCE rates need a further increase of SCE to reach values equal to those of normal cells might indicate a somewhat higher susceptibility of leukemic cells to DNA damage by MMC. This interpretation appears to be confirmed by the fact that the inhibition of cellular proliferation at higher MMC doses considerably reduced the number of leukemic cells that was able to divide twice during a given culture time.

Adolescent↗

Sister chromatid exchange levels and cell cycle time in human bone marrow cells and lymphocytes.

The frequency of sister chromatid exchange (SCE) and the cell-cycle-specific pattern of mitoses were analyzed at the same time in normal bone marrow cells and lymphocytes of six healthy donors. The SCE frequency was found to be significantly higher in lymphocytes. The cell-cycle-specific pattern revealed significantly shorter cell cycle times for normal bone marrow cells as compared with those of phytohemagglutinin (PHA) stimulated lymphocytes. Chromosomes of bone marrow metaphases displayed a more contracted morphology.

Adolescent↗

Chromosome changes in soft tissue sarcomas.

An analysis of chromosome aberrations in human tumors was performed in 29 cases of soft tissue sarcoma. The tumor tissues were disaggregated with collagenase and the cells cultured for 2-3 days. Analyzable metaphases were obtained in 15 cases, 4 of which showed only normal karyotypes. The remaining 11 tumors showed various numerical and structural abnormalities in their karyotypes: 8 tumors were near-diploid and the remaining 3 were near-triploid. G- and Q-banding analyses revealed clonal abnormalities in the 11 cases with the presence of marker chromosomes; 15 different chromosomes were involved in chromosome rearrangements, chromosomes 1 and 2 being the most frequently affected. Because of the heterogeneity of the tumor group investigated (neurogenic sarcoma, 2 liposarcomas, neurofibrosarcoma, synovial cell sarcoma, fibrosarcoma, mesothelioma, leiomyosarcoma, rhabdomyosarcoma, Ewing's sarcoma, and hemangiopericytoma), it was impossible to reach any conclusion on the specificity of the cytogenetic abnormalities for a particular tumor type.

Adult↗