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Biomedical subjects

H Löffler

Publications and source records attributed to H Löffler.

At least 163 records · Page 9Linked to original sources

Classification of malignant cardiac tumors with respect to oncological treatment.

Because of the small incidence of primary cardiac neoplasms there have been no randomized clinical trials to establish rational therapeutic strategies. Surgery is the first choice of therapy in all patients with small cardiac neoplasms. But it is not known whether adjuvant chemotherapy may be benefitial in patients in whom "curative" surgery has been performed. Chemotherapy must be considered as the first choice of therapy in primary cardiac tumors with extracardiac metastases. Combination of several agents is more effective than single-agent therapy. Radiation should be applied in less sensitive tumors only if surgery is not feasible and prior chemotherapy has failed. In patients in whom cardiac surgery was performed with a curative aim, chemotherapy but not radiation is the adjuvant therapy of choice. Patients with metastatic tumors to the heart should be treated according to the established rules for the involved tumor. Therapeutic strategy depends on the kind of tumor and the cardiac structure involved. Tumor spread to the pericardium will cause pericarditis or pericardial effusion up to pericardial tamponade. Instillation of tetracyclines, isotopes and chemotherapeutic agents in the pericardial space have been successfully applied to prevent recurrent effusion. Radiation did prolong life in patients with pericardial metastases as compared with repeated pericardiocentesis. Additional cardiac damage may be induced by radiation as well as by drugs. A trial with chemotherapy can be useful in all sensitive cardiac tumors.

Antineoplastic Combined Chemotherapy Protocols↗

[Clonality and stem cell defects in the molecular pathology of chronic myeloproliferative disorders].

The chronic myeloproliferative disorders (CMD) are characterized by sustained or progressive proliferations of bone marrow cells, affecting one or more lineages in varying combinations. They are classified in 4 subgroups but transitional forms and transformations among the different entities are common. Analysing RFLPs and methylation patterns of X-chromosomal genes we could show, that in each entity granulocytes as well as bone marrow cells are of monoclonal origin. These findings support the view that all forms of CMD have in common that they arise from a multipotent hematopoietic stem cell. CML can be differentiated from all other forms of CMD by the Philadelphia-chromosome which on the molecular level has been revealed as bcr-abl gene junction. We investigated 258 cases of CMD for rearrangement of the bcr gene and found that it selectively occurred in CML. The methods applied can be of diagnostic value in differentiating reactive from neoplastic proliferations by analysis of clonality, and in differentiation of CML from other types of CMD by detection of the bcr-rearrangement.

Bone Marrow↗

Pharmacokinetics of auranofin a single dose study in man.

Three days after cholecystectomy 7 patients were given a single dose of auranofin (5 tablets Ridaura = 4.35 mg gold). Gold was detected in samples of blood, plasma, urine, bile and feces. The determinations were carried out using instrumental neutron activation analysis. The mean gold concentrations reached maximum in blood and plasma after 2 h and in urine and bile after 16 h. The mean terminal half-lives were 7.6 days (blood), 15 days (plasma) and 6.5 days (bile). Cumulative amounts of gold excreted in bile, urine, and feces were 1.6, 4 and 40%, respectively.

Aged↗

Appearance of a transient inv(14)(q11q32) in a case of B cell chronic lymphocytic leukemia.

The inv(14)(q11q32) has been reported to be a specific chromosome aberration in T-cell chronic lymphocytic leukemia (T-CLL) and different types of T-cell lymphomas. Here, the first case of B-CLL with a clonal inv(14)(q11q32) in a phytohemagglutinin-stimulated bone marrow culture is presented. In a subsequent study 9 months later, tetradecanoyl-o-phorbol-13-acetate stimulated blood and bone marrow cultures revealed a clone with a t(1;11)(p13.2;q23.1) and an aberrant chromosome 17.

Aged↗

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia.

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

Adult↗

[Induction of remission in severe lupus erythematosus by intensified therapy].

11 patients with severe SLE were treated with plasmapheresis and subsequent pulse cyclophosphamide. In all patients rapid improvement was observed. After another 6 months of immunosuppression any treatment was withdrawn. The remissions remained stable in 6/8 patients during the follow-up period of 7-33 (mean: 21) months.

Cyclophosphamide↗

Does active rheumatoid arthritis affect intestinal iron absorption?

One of the causes of anaemia in rheumatoid arthritis is thought to be defective iron absorption. In this study the 59Fe absorption in patients with active rheumatoid arthritis is measured and correlated with the results for bone marrow iron stores (and in some cases with the iron stores in the terminal duodenum), which were assessed simultaneously with semiquantitative methods, and with the serum ferritin concentration. In 11 patients with rheumatoid arthritis and increased bone marrow iron stores, iron absorption was decreased. In five patients it was normal and in three further patients, whose bone marrow iron stores were depleted, iron absorption was maximally increased. According to the results both intestinal malabsorption and defective iron absorption can be excluded as causes.

Adult↗

[Intensive combined therapy for high-risk ALL patients].

In the risk-adapted multicenter trial (02/84) for adult ALL the effectiveness of a consolidation therapy consisting of VM26 and Ara-C for high-risk patients was tested. Out of a total of 442 patients in the study, 79.2% achieved a complete remission. For the 182 high-risk patients the median remission duration is 17 months and the probability of being in continuous complete remission (CCR) is 34%. Improved results were found for elderly ALL patients between 35 and 65 years of age, whose median remission duration and CCR rate are 19 months and 40% respectively, compared to 15 months and 26% in the former study 01/81. The consolidation therapy has apparently also benefited patients with the immunological subtype c-ALL, for whom the CCR rate at 3 years is 53% in comparison to the previous value of 34%.

Adolescent↗

Comparison of cyclophosphamide, cytarabine, and etoposide as immunosuppressive agents before allogeneic bone marrow transplantation.

Etoposide and cytarabine have been shown to exert high antileukemic activity and are currently under study as preparatory agents before allogeneic bone marrow transplantation. However, data concerning their engraftment-promoting potency are scarce. Therefore, we tested these agents in LEW rats receiving a myeloablative dose of busulfan followed by transfer of F1 (CAP X LEW) marrow, which is unable to induce a graft-v-host reaction (GVHR). Since busulfan by itself has only minor immunosuppressive potency, graft rejection ensues unless etoposide, cytarabine, or cyclophosphamide provide additional immunosuppression to facilitate durable engraftment. Before allogeneic bone marrow transplantation in humans, 120 mg/kg of cyclophosphamide, 60 mg/kg of etoposide, or 900 mg/kg of cytarabine are the standard doses given in conjunction with total body irradiation. Seventy-five percent of these doses administered in addition to busulfan resulted in rejection rates of 75% for cytarabine and 58% for etoposide, respectively, whereas no rejections were observed with cyclophosphamide. These data indicate that etoposide and cytarabine are inferior to cyclophosphamide in their rejection-preventing potential. Using either of these agents as substitutes for cyclophosphamide before allogeneic bone marrow transplantation may increase the risk of graft rejection in HLA-mismatched bone marrow transplantation and, in case of HLA identity, if T-depleted marrow is administered.

Animals↗

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗

Application of a microseparation technique allowing for extensive marker studies on small bone marrow specimens.

The characterization of surface and intracellular markers of hematopoietic cells by immunocytochemical methods is widely used. While examination of cells of the peripheral blood can easily be performed, investigations of bone marrow cells can be hampered by technical difficulties in labeling routine marrow smears or by limited size of specimens required for cytocentrifugation. A simple and highly efficient method for isolation of bone marrow cells by a microseparation technique is described. Only two to three drops of a routine bone marrow aspirate are necessary for preparation of up to 100 cytocentrifuge slides thereby exceeding separation efficiency of conventional gradient centrifugation by three- to more than four-fold. The application of the method for marker studies on normal marrow and marrow from patients with hematologic malignancies is exemplified.

Antibodies, Monoclonal↗

Postinduction and preremission chemotherapy alternatives for adult AML: three multicenter studies of the AML Cooperative Group.

Major chemotherapeutic alternatives for AML have been implemented and compared in three multicenter studies, including a total of 877 adult patients of all ages. The results strongly suggest that myelosuppressive postinduction treatment is a prerequisite for the achievement of long-term remissions. In addition, it was possible to establish an important antileukemic effect of monthly maintenance chemotherapy. Initial results from an intensive two-course preremission therapy concept revealed good practicability and acceptable toxicity, as well as promising response and remission durations by this new approach.

Antineoplastic Combined Chemotherapy Protocols↗