Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma.

Background: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback.

Incidence of viral markers and evaluation of the estimated risk in the Swiss blood donor population from 1996 to 2003.

Among the well known transfusion-associated risks, the transmission of pathogenic viruses is regarded as one of the most serious. Over the past two decades, a series of overlapping safety procedures have been successively implemented to minimise this risk. It is now generally considered that the risk of transmitting viral infections via blood products is very low in developed countries.

Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK).

Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML).

Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia.

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML.

MTS1 expression and prognosis in acute myeloid leukemia.

MTS1, a tumor suppressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol.

Evidence for persistence of human parvovirus B19 DNA in bone marrow.

A nested polymerase chain reaction assay (nPCR) was used to investigate the potential of human parvovirus B19 DNA to persist in blood or bone marrow samples obtained either from blood donors or cadaveric bone donors or from patients presenting with clinical signs of parvovirus B19 infection. The presence of parvovirus B19 specific antibody in blood was tested by enzyme immunoassay (EIA). B19 virus genome was not detected in any blood sample of 115 blood donors, of whom 92 (80%) had anti-B19 IgG antibody only as an indication of past infection.

Five putative drug resistance parameters (MDR1/P-glycoprotein, MDR-associated protein, glutathione-S-transferase, bcl-2 and topoisomerase IIalpha) in 57 newly diagnosed acute myeloid leukaemias. Swiss Group for Clinical Cancer Research (SAKK).

Unlabelled: Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myeloid leukaemia (AML) from a Swiss Phase III multicentre study (SAKK 30/85), we measured the m-RNA expression of the genes from the multidrug resistance gene 1 (MDR1), the multidrug resistance associated protein (MRP), glutathione-S-transferase (GST) pi, bcl-2 and topoisomerase (topo) IIalpha. P-glycoprotein (p-gp) was measured by Western blot, and GST activity by functional assays. To analyse progression-free (PFS) and overall survival (OS), parameters were prospectively divided into "low" and "high" groups, according to their median values (exceptions: MDR1 and p-gp).

Post-remission therapy of adult acute myeloid leukaemia: one cycle of high-dose versus standard-dose cytarabine. Leukaemia Project Group of the Swiss Group for Clinical Cancer Research (SAKK).

Background: Intensification of post-remission therapy improves the cure rate of acute myeloid leukemia (AML) but is often accompanied by unacceptable toxicity. From 1985 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial to evaluate the effectiveness of one single postremission course of high-dose cytarabine (HDAC) in terms of leukaemia-free and overall survival in adults with de novo AML.

Patients And Methods: Adult (15-65 years) AML patients in remission after two induction courses were randomly assigned to one consolidation course either with standard (SDAC: 100 mg/sqm 24 hours infusion over seven days) or with high-dose cytarabine (HDAC: 3000 mg/sqm every 12 hours as one-hour-infusion for six days).

Intensive induction/consolidation therapy without maintenance in adult acute lymphoblastic leukaemia: a pilot assessment. Working Party on Leukaemia of the Swiss Group for Epidemiologic and Clinical Cancer Research (SAKK).

Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy.

Factors associated with transfusion requirements during treatment for acute myelogenous leukemia.

Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia.

[Therapeutic plasmapheresis--a critical review in the light of the current literature].

For centuries it has been the dream of many physicians to cure illnesses by eliminating disease provoking substances which are thought to circulate in the human body. Technical developments during the past 20 years have made therapeutic plasma exchange (TP) a useful procedure for clinical application. Because of the lack of well controlled studies the true benefit of the method remains speculative in many clinical situations.

[Action of various growth factors on bone marrow cultures in acute myeloid leukemia (ALM)].

In an attempt to detect residual leukemic cells during remission, we examined differences in the stimulatory capacity of colony stimulating factors (CSF) added to agar cultures of AML patients at diagnosis/relapse (group I) and in remission (II), or of normal controls (III). Supernatant from the human bladder carcinoma cell line 5637 and human recombinant granulocyte-macrophage-CSF were compared with supernatant from human placenta as standard. Group I showed wide patient-to-patient variations.

Relapse cell population differs from acute onset clone as shown by absence of the initially activated N-ras oncogene in a patient with acute myelomonocytic leukemia.

We have conducted a follow-up study of a patient with myelomonocytic leukemia exhibiting an N-ras mutation (Gln61----Lys61) using the polymerase chain reaction method and synthetic oligonucleotide hybridization probes. This method allowed us to detect as little as 3% of N-ras-mutated cells within a population. When the patient went into clinical remission, the mutation became undetectable.

Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.

DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT transitions in codon 12 and one CAA----AAA transversion in codon 61. One case exhibited homozygosity for the mutation.

Long-term results of two Swiss AML studies.

The Swiss group for clinical cancer research (SAKK) completed two first line protocols for the treatment of acute myelogenous leukemia (AML). In the first protocol (SAKK AML 74, from August 1974 to April 1977; 107 patients) the effectiveness of immunization with viral oncolysate during maintenance treatment was tested. After successful induction treatment, the patients were randomized in two groups: Group A: monthly maintenance chemotherapy for 2 years and group A+IT, which received the same maintenance chemotherapy regimen plus, on day 15, injection of viral oncolysate.

Efficacy and clinical cross-resistance of a new combination therapy (AMSA/VP16) in previously treated patients with acute nonlymphocytic leukemia.

We investigated the tolerance, efficacy, and clinical cross-resistance of a new combination chemotherapy in 38 patients with previously treated acute myeloblastic leukemia (AML). It consisted of 120 mg2/d 4'(9-acridinylamino) methanesulfon-m-Anisidide (m-AMSA) in a one-hour infusion and 80 mg/m2/d etoposide (VP-16) in a 24-hour infusion, both administered for 5 days. The first 27 patients also received vinblastine, 6 mg/m2 on day 8, but this therapy was discontinued because of intestinal complications.

[Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody].

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL.

Heterogeneity of Ia antigen expression on myeloblastic leukaemias: correlation with stage of maturation defined by cytochemical markers.

The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS-D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15-100%): the MS2 group of 14 cases with 10-70% NCAE positive cells (SB: 65-100%) and the MS3 group of 11 cases with 70-100% NCAE positive cells (SB: 89-100%). Ia expression was determined by complement-dependent cytotoxicity, immunofluorescence and immunoperoxidase methods.

Phase-I trial of 4-demethoxydaunorubicin in acute leukaemias.

Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin. Dosages were escalated from 7 mg/m2/d to 15 mg/m2/d for 3 consecutive days. One patient achieved a partial remission and antitumor activity was seen in most other patients.

Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival.

To investigate the value of maintenance chemotherapy after early consolidation treatment, an attempt was made to induce remission in 162 previously untreated patients, age-range 7-65 years (median 43). The 74 patients who were still in remission after early consolidation treatment (given for 3-5 months) were assigned to either maintenance chemotherapy every 8 weeks for 2 years or to observation only. After a median observation period of 44 months there was no difference between the groups in duration of remission or survival.

[Unrecognized atypical tuberculosepsis in generalized hematologic neoplasms].

Differential diagnosis and therapy of 4 cases (3 of acute myelogenous leukemia and 1 of Hodgkin's disease, stage IVB) of septic exacerbation of febrile course in generalized hematologic neoplasms under intensive treatment are described. The infectious process of 3 cases was confirmed as generalized tuberculosis only at autopsy. The incidence in over 250 patients (1973-1979) was 1.

[Diagnostic and therapeutic importance of splenectomy in patients with non-Hodgkin's lymphoma].

Whereas the contribution of exploratory laparotomy in Hodgkin's disease is well characterized, its value in Non-Hodgkin lymphoma (NHL) is not yet defined. This retrospective analysis of 31 cases is a contribution to the ongoing discussion. Laparotomy/splenectomy (LS) was done in 17 patients for diagnostic reasons and in 14 with therapeutic intent.