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Biomedical subjects

J Mittermüller

Publications and source records attributed to J Mittermüller.

33 records · Page 2Linked to original sources

[Listeriosis in malignant diseases].

Listeriosis occurred in two patients, a 46-year-old woman and a 41-year-old man, in the course of an underlying malignant disease. The woman had a metastasizing pancreatic apudoma, requiring partial pancreas resection with splenectomy. After the end of cytostatic treatment she developed headaches and fever up to 40 degrees C. Listeria monocytogenes was demonstrated in the blood and cerebrospinal fluid. She went into coma on the day after hospital admission and, despite antibiotic administration, she died on the fourth day of treatment. The 41-year-old man was suspected of having an angioimmunoblastic lymphoma. Severe haemolytic anaemia (haemoglobin 4.4 g/dl) was treated with glucocorticoids, massive blood transfusions and splenectomy, at first without success. During immunosuppressive treatment with prednisone and cyclophosphamide the haemoglobin rose. But he was still feverish with nocturnal sweating. Neurological symptoms of motor aphasia, cranial nerve deficits and incomplete hemiparesis rapidly developed. Computed tomography revealed a focus in the internal capsule. Blood culture grew Listeria. The focal encephalitis healed with minor sequelae after antibiotic treatment. Both patients had hypogammaglobulinaemia, but no granulocytopenia. It is stressed that listeriosis should be included in the differential diagnosis in cases of septicaemia or cerebral infection occurring in the course of malignant disease.

Adult↗

Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.

From July 1986 to 1990, 65 patients with deep-seated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40 patients) had received ifosfamide-containing drug regimens before entering the RHT study, 26% (17 patients) were pretreated by surgery and/or radiation and 12% (8 patients) were treated primarily. A total of 426 RHT treatments (mean 6.6 RHT/patient) were applied predominantly within the pelvic region (82%) bearing relative large tumours (mean volume 500 cm3). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1-5), etoposide (100 mg/m2, days 1, 3, 5) and 2-mercaptoethanesulphonic acid (mesna; 300 mg/m2 x 4, days 1-5) with RHT only given on days 1 and 5 in repeated cycles every 4 weeks. Detailed thermal mapping by invasive thermometry was performed in all patients. In 61 patients evaluable for tumour control the overall objective response rate including 9 complete responders (CR), 4 partial responders (PR) and 8 patients with favourable histological response (FHR) was 34% (95% confidence limits, 23%-46%). Following CR, the patients are alive and remain disease-free (mean disease-free survival 15.6 months). Of the patients with PR and FHR, 3 died from metastatic and/or local disease after 4, 17, and 39 months, and 1 patient died from other disease (acute myelocytic leukemia) after 27 months. The other 8 patients remain stable at 29, 25, 17, 11, 10, 8, 7, and 6 months. Twenty-two patients revealed no change and 18 patients showed local tumour progression (PD). Side-effects of RHT were tolerable and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. By analysis of temperature parameters, the time-averaged temperatures of all RHT treatments calculated for 20% (T20), 50% (T50) or 90% (T90) of measured tumour sites differed significantly between responders (CR + PR + FHR) and non-responders (PD), respectively (T20, P = 0.001; T50, P = 0.0005; T90, P = 0.0001). the data further support a strong potential for ifosfamide plus etoposide combined with RHT in pretreated patients with advanced sarcomas.

Adolescent↗

Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.

Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.

Adult↗

Improved survival following HLA-incompatible bone marrow transplantation. Munich Cooperative Group of Bone Marrow Transplantation.

In most centers allogeneic bone marrow transplantation is restricted to patients with HLA-identical siblings as donors. We have transplanted 16 patients with marrow of donors other than HLA-identical siblings. Seven patients were grafted in the years 1978 until 1984. Six died of transplant complications and one of recurrent leukemia. More recently 9 patients were transplanted following an improved immunosuppressive conditioning treatment derived from experimental studies in dogs. Four are alive and in continuous remission between more than 2 months and 2 years. 5 patients died, 3 from fungal infections, one from recurrent leukaemia and one early from endothelial leakage syndrome. Our results indicate that intensified immunosuppressive conditioning may improve the results of marrow transplantation from HLA-haploidentical donors.

Adolescent↗

Myeloablative conditioning for marrow transplantation in myelodysplastic syndromes and paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are disorders of pluripotent stem cells resulting in haematopoietic insufficiency which can be cured by marrow transplantation. The extent of myeloablative conditioning necessary for elimination of the non-malignant and premalignant clones is not known. We report our results of marrow transplantation with and without myeloablative conditioning in two patients with PNH and seven patients with MDS. Conditioning was not used in a patient with PNH and a monozygotic twin as donor. In this patient the disease remained unchanged. Myeloablative treatment with busulphan (BUS) in addition to immunosuppression with cyclophosphamide (CY) was used for conditioning in a patient with PNH and a 2-year-old boy with chronic myelomonocytic leukaemia (CMML). Fractionated total body irradiation (FTBI) and CY was used in six patients with refractory anaemia with excess of blasts (RAEB) and RAEB in leukaemic transformation (RAEB-T). Haematopoiesis was fully restored in all patients conditioned with myeloablative treatment except for a patient in leukaemic transformation with myelofibrosis and a HLA-DR-incompatible donor. Chimerism was complete in all patients except for the 2-year-old boy conditioned with BUS and CY. Our results and those reviewed in the literature indicate that myeloablative conditioning with either BUS or FTBI is advantageous for marrow transplantation in PNH and MDS.

Adult↗

Epstein-Barr virus-positive recipient type B-cells survive in a "complete chimera" after allogeneic bone-marrow transplantation.

Latency of Epstein-Barr virus infection may be generated by surviving immortalized B cells or by continuous re-infection. EBV-positive B-cell tumors have been found following bone-marrow transplantation (BMT) and were of donor type in the few cases investigated. We established a B-cell line from the bone marrow of a patient in complete remission following allogeneic BMT for aplastic anemia 18 months post-grafting. Differences in sex and isoenzymes allowed an exact determination of chimerism in our case. While the patient showed persistent complete chimerism of all cell lineages, cells grown in culture were of recipient type. They expressed B-cell markers, showed a monoclonal rearrangement of the immunoglobulin genes and carried EBV-associated antigens. As direct preparations of cells from the patient did not contain detectable recipient-type cells, it appeared likely that small numbers of EBV-transformed B cells of the recipient survived for long periods in this patient. For the development of secondary B-cell neoplasms in vivo, additional patho-physiological steps like severe graft versus host disease or T-cell suppression are obviously required because the patient was still free of lymphoma 3 years post-grafting.

Acid Phosphatase↗

In vivo differentiation of leukaemic blasts and effect of low dose Ara-C in a marrow grafted patient with leukaemic relapse.

The possible induction of differentiation of leukaemic cells by low dose cytosine arabinoside (Ara-C) was studied in an human chimaera with leukaemic relapse. A 35-year-old woman had been grafted with bone marrow from her HLA identical sister and developed a leukaemic relapse of the host type demonstrated by typing phosphoglucomutase 1 isoenzymes. Before treatment with low dose Ara-C only leukaemic cells and a part of the mature granulocytes were of host type. Lymphocytes, platelets and erythrocytes were still of donor type. The leukaemic cells and the mature host type granulocytes disappeared and the patient went into complete remission after treatment with low dose Ara-C. The results indicate that (a) the leukaemic blasts could differentiate in vivo into mature granulocytes, (b) leukaemic transformation was limited to granulopoiesis, and (c) low dose Ara-C acted as a cytotoxic drug instead of inducing differentiation of host type granulopoiesis.

Adult↗

Cytotoxic action of low dose Ara-C. Investigations in a marrow grafted patient with relapse.

A 35-year-old woman relapsing from acute myeloid leukemia (AML) after a bone marrow transplantation (BMT) achieved complete remission by low dose Ara-C treatment. Phosphoglucomutase 1 (PGM 1) isoenzyme analysis gave evidence for complete chimerism before relapse, whereas relapsing leukemia was autochtonous. Low dose Ara-C treatment cleared the marrow of leukemic blasts and reestablished normal in vitro growth patterns of myelopoiesis. Disappearance of autochthonous cells and regrowth of transplanted hematopoiesis was shown by PGM 1 isoenzyme analysis. Thus, low dose Ara-C exerted its action--at least in this patient--by cytotoxic mechanisms.

Adult↗

Genetic study of orosomucoid by isoelectric focusing and immunoprinting in patients with carcinoma.

The carbohydrate moiety of the orosomucoid (ORM) molecule shows microheterogeneity [1] and the pteridine-containing variant seems to be tumor-specific [2-4]. However, there also exists a genetic (protein-related) polymorphism coded by the ORM1 and ORM2 loci on chromosome 9 [5, 6]. To investigate the relationship between ORM1 gene products and the development of carcinoma, we analyzed the ORM1 phenotypes of desialated sera from 125 patients with carcinoma. The allele frequencies were estimated for ORM1*F1 0.556, ORM1*F2 0.012 and ORM1*S 0.432. In comparison to healthy individuals from the same geographical area [6] the ORM1 S phenotypes are significantly more frequent in carcinoma patients. The patients' sera frequently showed additional ORM-positive proteins which focused slightly cathodically to the ORM 2 A band. These proteins may represent posttranslational modifications of the ORM1*S allele product. Whether these modifications are tumor-specific and related to the carbohydrate moiety of the molecule must be confirmed in further studies.

Alleles↗

Repeated blast crisis (BC) of changing morphology, immunologic phenotype and cytogenetics in chronic myeloid leukemia (CML).

The clinical course of a 66 year old male with CML who experienced several " relapse " BC of changing morphology, immunologic phenotype and cytogenetics is reported. The first BC was of lymphoblastic phenotype, the second of myeloid, the third again of lymphoblastic, and the fourth, terminal BC was not further characterized or treated. Whereas a phenotypic switch from lymphoblastic to myeloid has been documented twice, the sequence of myeloid followed by a lymphoblastic BC has, to our knowledge, not been reported so far. Lymphoblastic BC responded to a combination of vindesine/prednisone and 6-mercaptopurin. Myeloid BC was controlled by an AML-type induction regimen consisting of daunorubicin and cytosine arabinoside. This unusual case demonstrates that relapse BC is not necessarily of the same morphologic and phenotypic lineage as the preceding BC. Moreover, treatment should be adjusted to the predominant cell type in order to prolong survival.

Aged↗