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Biomedical subjects

C Clemm

Publications and source records attributed to C Clemm.

At least 55 records · Page 3Linked to original sources

Spontaneous Epstein-Barr virus transformed B-cell line sharing the identical immunoglobulin gene rearrangement with acute myeloid leukemia.

Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.

Adult↗

Time-effect relationship of chromosome aberrations in peripheral lymphocytes after radiation therapy for seminoma.

The time-effect relationship of dicentrics and cells containing unstable chromosome abnormalities (Cu cells) was studied in peripheral lymphocytes of 40 blood samples from 23 patients suffering from seminoma during a time period of 0-1720 days after radiation therapy. Nine patients were studied before treatment. Since the half-time for the disappearance of damaged cells from circulating blood is an increasing function of post-exposure time it can only be expressed as a differential value. The present model discriminates between the mean lifetime m for lymphocytes and a parameter q which is the differential half-time for the decline of damaged cells immediately after exposure (t = 0). If the time t is short compared with m the decline is asymptotically time-hyperbolic rather than exponential and can be described by q only. According to recalculations of previous data, comprising 30 years post exposure, m approximates 10 years. Differential half-times can be derived for any time post treatment within the analysed time period for the decline of the incidence of dicentrics. For example at the end of therapy (t = 0) the differential half-time was calculated to be 0.4 years and at 1720 days post exposure 3.6 years resulted. The corresponding values for the percentage of Cu cells cannot be derived for t = 0; at 1720 days 3.9 years resulted.

Adult↗

Significance of salvage lymphadenectomy in the therapeutical concept of advanced nonseminomatous germ cell tumors.

A retrospective study reports 65 patients with metastatic disease from nonseminomatous germ cell testicular tumors who underwent a salvage lymphadenectomy either to remove a residual mass or to confirm a complete clinical response after polychemotherapy. Scarring was found in 23 patients (35%), differentiated teratoma in 25 patients (39%) and residual cancer in 17 patients (26%). Of the 12 patients staged as complete responders 2 were found to have cancer, 4 teratoma and 6 fibrosis. Neither tumor markers nor CT scan could accurately predict which patients with residual masses would have cancer, mature teratoma or necrosis. Thus needle biopsy or limited resection is inadequate in its ability to detect persistent vital tumor. After a follow-up of 10-106 months 49 patients (75%) are living with no evidence of disease. 12 patients (19%) died of tumor progress. The most critical prognostic determinant was the nature of the tissue resected. 21 (91%) of 23 patients with only fibrous or necrotic elements are living with no evidence of disease. However, of 17 patients with persistent cancer in the resected tissue only 8 patients (47%) fared well. Our experience confirms the original concept which called for postchemotherapeutic tumor surgery in all patients who demonstrated either a partial or complete clinical response.

Adult↗

Combination chemotherapy with vinblastine, ifosfamide and cisplatin in bulky seminoma.

Since 1982, 24 patients with bulky seminoma were treated with the VIP-regimen consisting of vinblastine 6 mg/m2 days 1+2, ifosfamide 1.5 g/m2 days 1-5, cisplatin 20 mg/m2 days 1-5. One patient showed primary progression, another patient partial remission, and one patient died during the first cycle. All the other patients had complete remission (21/24 = 87%), which was documented histologically in 9 patients. One patient relapsed but obtained complete remission after repeated treatment. Thus 21 patients are currently living without disease after a median observation time of 30+ months. Bone marrow toxicity was severe, leading to dose reduction in more than 50% of the patients. No other severe side effects were observed. We conclude that the regimen is highly effective in bulky seminoma. Reduction of the vinblastine dose is recommended because of bone marrow toxicity.

Adult↗

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↗

[Value of preoperative thrombocyte marking in patients with idiopathic thrombocytopenic purpura].

51Cr-platelet kinetic studies were performed in 77 patients with idiopathic thrombocytopenic purpura. The sequestration site was splenic for 63, splenic/hepatic for 7 or hepatic for remaining 7 patients. In 20 patients platelet survival was extremely shortened to 0-3 h, whereas only 26 patients had a survival time of more than 24 h. Those patients with low platelet counts also had a very short platelet survival time, whereas patients with higher platelet counts (greater than 50 x 10(9)/l) had longer platelet survival times. 51 patients (66%) were splenectomized following the kinetic studies. 25 patients who had a splenic sequestration site had normalized platelet counts and 6 patients had platelet counts between 80-149 x 10(9)/l 12 months after splenectomy (i.e. in 92% of cases with splenic sequestration site a full or partial remission). Of the 11 patients with a hepatic or splenic/hepatic sequestration site, 2 patients had full remission, 1 partial remission, 3 patients had minimal improvement and 5 other patients were treatment failures in respect to the splenectomy.

Adolescent↗

Lymphangiomyomatosis: a report of three cases treated with tamoxifen.

Three cases are reported of lymphangiomyomatosis with pulmonary and abdominal manifestations. Two had a chylous pleura effusion, while the third presented a retroperitoneal manifestation, which was completely resectable. Antiestrogen therapy with tamoxifen was administered in all three cases. Two patients died of pulmonary progression after 4 months of therapy. The third is still alive, with stable disease for more than 6 years, and has been receiving tamoxifen for 66 months. These observations indicate that antiestrogen treatment may be as effective as oophorectomy when started at an early stage of the disease.

Abdominal Neoplasms↗

Benefit and costs of follow-up programs in nonseminomatous germ cell tumors of the stages IIb-IV: the Munich experience.

Since 1979 we have seen 197 patients with nonseminomatous germ cell tumors (NSGCT) of the stages IIb-IV. 185 of these are evaluable (3 lost to follow-up, 9 still in treatment). The majority of the patients was given platinum-vinblastine-bleomycin treatment (PVB). 138/185 (74.6%) have achieved a first complete remission (CR), and 131/185 (70.8%) are currently found with no evidence of disease (NED). All patients in CR have been followed by physical examinations, blood chemistry including tumor markers, and chest X ray (years 1 and 2: 8 times; year 3: twice; years 4 and 5: twice) and by abdominal computer tomography (CT; years 1 and 2: 6 times; year 3: twice; years 4 and 5: twice). So far this follow-up procedure has been performed for a total of 326 patient years costing approximately $215,000. 18/138 patients (13%) were found in the first relapse. 13/18 could achieve a 2nd CR under salvage therapy. 2 of these patients were found in a 2nd relapse and 1 of these was brought into a third CR. 1 patient died in CR from reasons unrelated to NSGCT. The 20 first and second relapses were detected with clinical symptoms (6 times), chest X ray (6 times), abdominal CT (5 times), and tumor marker elevation (3 times). This represents 14 relapses detected by follow-up examinations without clinical symptoms. Only 1/6 patients complaining of clinical symptoms as a first sign of the 1st recurrence achieved a second CR, and 5/6 died of progressive disease, whereas all 12 patients with first relapses detected without clinical symptoms during follow-up could be brought into second CR. Although this is a retrospective analysis and 3/6 patients with symptomatic relapses had additional brain lesions, these data, with due caution, tend to argue in favor of close follow-up programs with monitoring additional to physical examination for patients with NSGCT in CR. Furthermore, 15/18 first relapses (83%) were found within the first 2 years and 3/18 later. Since all 3 patients detected with a late recurrence achieved a second CR, at least 5 years of follow-up seem justified.

Cost-Benefit Analysis↗

Vinblastine-ifosfamide-cisplatin treatment of bulky seminoma.

Eighteen patients with pure seminoma in advanced Stages IIC-IV of disease were treated with VIP combination chemotherapy consisting of vinblastine (6 mg/m2, days 1 and 2), ifosfamide (1.5 g/m2, days 1 to 5), and cisplatin (20 mg/m2, days 1 to 5). Eleven patients had Stage IIC, four had Stage III, three had Stage IV, and two had primary extragonadal seminoma. Primary histologic diagnoses were typical seminoma in 15 patients and anaplastic seminoma in three patients. Human chorionic gonadotropin (HCG) levels were elevated to 350 U/1 in eight patients; alpha-fetoprotein (AFP) levels were always normal. No primary lymphadenectomy was carried out. Seven of 18 patients had prior radiotherapy and were treated because of relapse or progression. There was one early death and one patient has not yet completed therapy. Of 16 evaluable patients, 14 reached complete remission (CR) (88%), which was documented surgically in six cases, whereas in the non-pretreated group, all nine patients reached CR and in the pretreated group, CR could be induced in five of seven patients (71%). The remission duration ranged from 6+ to 41+ months (median, 29+ months). No relapse has occurred. The bone marrow toxicity of VIP was remarkable. Because of leukopenia below 1000/mm3 and/or thrombopenia below 50,000/mm3, dose reduction and interval prolongation were necessary in 10 of 16 patients, especially in all those who were pretreated. Even though it is not superior to other platin-based regimens, VIP chemotherapy is highly effective in bulky seminoma with and without prior radiotherapy.

Adult↗

[The Munich follow-up program in advanced non-seminoma testicular tumors. Benefits and costs].

Results in 185 of 197 patients with non-seminomatous testicular tumours treated since 1979 were retrospectively analysed. Most of them had been given chemotherapy according to the PVB schedule. In 138 patients (75%) a first complete remission was achieved, and 131 (71%) are currently disease-free. All patients in complete remission were entered in a follow-up programme consisting of physical examination, laboratory tests including tumour markers, chest X-ray and abdominal CT. A total of 326 patient-years of follow-up has so far been carried out at a cost of DM 650,000. A first relapse was detected in 18 patients (13%); 13 of them reached a second remission after further treatment. The 20 first and second relapses were detected by clinical symptoms (n = 6), chest X-ray (n = 6), abdominal CT (n = 5), or a rise in tumour markers (n = 3). Only one of six patients in whom clinical symptoms were the initial evidence of a first relapse, obtained a second complete remission. The five others in this group died of progressive disease. In contrast, all the twelve patients whose first relapses were detected by follow-up investigations in the absence of clinical symptoms, obtained second complete remission. 15 of the 18 first relapses were detected within the first two years. All three patients with late relapses were brought into second complete remissions. On this evidence, follow-up for at least five years appears justified.

Follow-Up Studies↗

Missing Y chromosome in 2 patients with chronic myelocytic leukemia.

2 cases of chronic myelocytic leukemia (CML) without Y chromosome are reported. One is a 45-year-old man with Philadelphia-positive CML, and the other a 74-year-old patient with Philadelphia-negative CML. Cytogenetic analysis of bone marrow and peripheral blood cultures with and without PHA stimulation was carried out. The Philadelphia-positive patient died after 15 months, whereas in the case of the Philadelphia-negative patient, the survival time of 27 months exceeded the median survival time usually reported for Philadelphia-negative CML patients, thus indicating a prognostic relevance of the missing Y chromosome.

Aged↗

Clonogenic assays and engraftment in allogeneic bone marrow transplantation.

The significance of clonogenic assays for determining the hematopoietic potential of bone marrow grafts is still a matter of controversy. We determined the number of myeloid (GM-CFU), early erythroid (BFUe) and mixed (CFU-GEM) clones in 23 consecutive allogeneic bone marrow grafts. The growth of GM-CFU was stimulated by placental-conditioned medium, whereas both phytohemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) and 'pluripoietin' from the 5637 cell line served as equally efficient stimulators of BFUe and CFU-GEM growth. Plating efficiency (e.o.p.) of GM-CFU and numbers of myeloid and mixed progenitors transplanted per kg body weight were significantly lower in those patients who died in the aplastic phase 2-6 weeks postgrafting (n = 4). These data show that low numbers of clonogenic cells, in particular GM-CFU, indicate a higher risk of death from infection following bone marrow transplantation (BMT) and argue for a contribution of GM-CFU in the seeding of an aplastic bone marrow.

Anemia, Aplastic↗

Hyperdiploidy of 54 chromosomes with double Ph1 chromosome in lymphoid chronic myelocytic leukemic blast crisis.

Cytogenetic analysis of bone marrow cells in a 40-year-old man revealed a mosaic of two cell lines during blast crisis: one diploid with typical Ph1 chromosome (46 XY Ph1) and one with hyperdiploidy of 54 chromosomes with double Ph1 chromosome, trisomy 4, 6, 8, 18, 21 and duplication of the sex chromosomes X and Y. Immunological characterization showed common acute lymphoblastic leukemia antigen in 90% of the blasts. In spite of intensive chemotherapy the patient died in a third blast crisis 15 months after the first blast crisis, 3 months after successfully treated central nervous system relapse.

Adult↗

[Bleomycin-induced pulmonary infiltrations in the treatment of testicular cancer].

Under Cisplatinum/Vinblastine/Bleomycin treatment six of 82 patients with nonseminomatous testicular cancer developed a Bleomycin-induced pulmonary toxicity. After a total Bleomycin dose of 300-360 mg all six patients showed multiple nodular densities near the pleura in the basal lung areas on the computed tomographic scanning (CT). Disseminated interstitial infiltrates, mostly in the lower lung fields were spontaneously observed by means of chest X-rays in only one case. In two other cases only minimal changes were found retrospectively. In five cases the diffusion capacity did not decrease significantly. Diffusion capacity, vital capacity and oxygen fell significantly in only one case. The latter was also the only patient showing clinical symptoms. The lung changes were completely reversible in four patients 4-6 months after cessation of Bleomycin. In two patients there were reversible residual changes after a timespan of 20 and 24 months. Two patients received no further antineoplastic treatment, two were under maintenance therapy, two under further induction chemotherapy because of the assumption of lung metastases. None of the six patients show any evidence at present of testis tumor (observation period 17-34 months). It can be difficult to distinguish between Bleomycin-induced lung damage and tumor metastases by radiological means. We were able to differentiate by observing the clinical course of the six patients. In case of doubt a histological examination is strongly recommended.

Adult↗

[Differential diagnostic problem of distinguishing pulmonary infiltrates following bleomycin therapy from metastases].

Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest x-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases.

Adult↗

Plasma exchange and concomitant therapy in TTP.

Since plasma exchange was introduced in the management of thrombotic thrombocytopenic purpura (TTP) in 1977, patient survival rate has increased from 10 to 80%. However, approximately 50 subsequent case reports in the literature provide no consensus as to the optimal therapy. We review here 4 episodes of TTP in 3 patients. In all cases, treatment was started with intensive FFP plasma exchange combined with administration of antiplatelet agents and corticosteroids. Remission was achieved in 3 out of 4 episodes although all required individualization of the medication regimen. In the remaining patient, cytotoxic therapy (vincristine) and ultimately splenectomy were required to achieve stable remission. The variable clinical response to these therapeutic protocols indicates that TTP may not represent a single homogeneous disease entity but rather may involve various underlying pathologies. We conclude that the most effective present therapy for the management of TTP is daily plasma exchange with fresh frozen plasma infusions combined with antiplatelet agents and steroids. Vincristine and splenectomy should only be employed if this protocol proves ineffective.

Adolescent↗