R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group.

BACKGROUND: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. METHODS: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. RESULTS: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P=0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P=0.02). CONCLUSION: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

[Hydroxyurea-induced leg ulcers in patients with chronic myeloproliferative disorders]. / Hydroxyurea-inducerede underekstremitetsulcera hos patienter med kroniske myeloproliferative tilstande.

INTRODUCTION: Hydroxyurea (HU) is usually a well-tolerated antineoplastic agent, which is commonly used in the treatment of myeloproliferative disorders. Dermatological abnormalities are often seen in patients receiving long-term HU therapy. Leg ulcers have been reported occasionally. MATERIAL AND METHODS: We carried out a prospective and descriptive study of patients who developed leg ulcers while receiving HU therapy. RESULTS: Between 1.1.1997 and 1.2.1998, chronic cutaneous leg ulcers were found in five out of a total of 28 patients treated with HU. The average age was 76 years (64-87 years). Two patients had chronic myelogenous leukaemia in a non-accelerated phase, two polycytaemia vera, and one essential thrombocytosis. The average duration of HU therapy was 30 months (10-55 months) before ulcerations appeared. These were typically located on the malleolar and/or perimalleolar area, and were very painful. HU therapy was discontinued and replaced by busulphan or anagrelide. Within 1.5-11 months of discontinuation of the treatment, the wounds had healed or improved. DISCUSSION: We found a surprisingly high number of cutaneous leg ulcers in patients on HU therapy for chronic myeloproliferative disorders. We believe this disabling complication should be given greater attention and recommend that it is included in the description of the side effects of the drug.

Many unbalanced translocations show duplication of a translocation participant. Clinical and cytogenetic implications in myeloid hematologic malignancies.

If a translocation is followed by loss of one of the two derivative chromosomes, the result is an unbalanced translocation, showing monosomy for the segments making up the lost derivative. We have found that in most unbalanced translocations, a third event takes place: a morphologically normal copy of one of the two translocation participants is added to the karyotype. This creates a complex abnormal karyotype with monosomy, disomy, and trisomy for different segments of the translocation participants. We have examined 82 unbalanced translocations from 77 patients, 73 of whom had a myeloid hemopoietic malignancy. Acquisition of a normal copy of a translocation participant was found in 49 translocations. Twenty-five of these showed trisomy for 1q. In 16 of the 25 1q-trisomic cases the translocation was t(1;7)(q10;p10) (trisomy for 1q and monosomy for 7q). Patients with trisomy for 1q were younger than the remaining patients. Whereas those with t(1;7))(q10;p10) showed brief survivals, those with trisomy 1q but monosomy for regions other than 7q survived longer than the remaining patients. We conclude that most unbalanced translocations involve a partial trisomy, that 1q is trisomic far more frequently than any other segment, and that partial trisomy is associated with patient age and survival.

Glucagon and glucagon-like peptide 1: selective receptor recognition via distinct peptide epitopes.

Glucagon and glucagon-like peptide 1 (GLP-1) are homologous peptide hormones that are recognized by likewise homologous, but highly selective receptors. Analogs of glucagon and GLP-1, in which the divergent residues were systematically exchanged, were employed to identify the structural requirements for their selective receptor recognition. Substitutions in the NH2-terminal part of the glucagon molecule with the corresponding GLP-1 residues, as for example in [Ala2,Glu3]-glucagon and [Val10,Ser12]glucagon, reduced the binding affinity for the glucagon receptor several hundred-fold without increasing the affinity for the GLP-1 receptor. In contrast, introduction of GLP-1 residues into the far COOH-terminal part of the glucagon molecule, e.g. [Val27,Lys28,Gly29,Arg30]glucagon, had a minimal effect on recognition of the glucagon receptor, but improved the affinity of the analog for the GLP-1 receptor up to 200-fold. Similarly, substitutions in especially the far COOH-terminal part of the GLP-1 molecule with the corresponding glucagon residues, e.g. des-Arg30-[Met27,Asn28,Thr29]GLP-1, decreased the affinity for the GLP-1 receptor several hundred-fold (IC50 = 0.4-190 nM) without increasing the affinity for the glucagon receptor. Conversely, substitutions in the NH2-terminal part of the GLP-1 molecule impaired the affinity for the GLP-1 receptor only moderately. We conclude that the selective recognition of the glucagon and GLP-1 receptors is determined by residues located at opposite ends of the homologous peptide ligands. This conclusion is supported by the observation that a "chimeric" peptide consisting of the NH2-terminal part of the glucagon molecule joined to the COOH-terminal part of the GLP-1 molecule was recognized with high affinity by both receptors.

[Physicians' work load. A comparison between company physicians and general practitioners in private practice]. / Legers arbeidspress. En sammenlikning av bedriftsleger og privatpraktiserende allmennpraktikere.

The authors describe and compare the work load of 26 general practitioners and 17 company doctors. All of them worked full time. The information was collected by means of a structured telephone interview. The results indicate a higher work load among general practitioners than among company doctors. Despite this, the general practitioners plan to remain working longer than the company doctors do. In both groups of doctors there were some who believed they risked developing the "burn-out syndrome". This problem was found among the youngest doctors, female doctors and doctors with a large number of consultations daily.

[Myelomatosis. A study of 138 patients treated with melphalan, prednisone and vincristine with particular attention to the prognostic value of a stage subdivision]. / Myelomatose. En undersøgelse af 138 patienter behandlet med melfalan, prednison og vincristin med saerligt henblik på en stadieinddelings prognostiske vaerdi.

With the object of evaluating three recognized prognostic stage subdivision systems for myelomatosis, retrospective data from 138 patients treated from 1976 to 1986 were employed. During this period, uniform therapeutic principles were employed, viz interval treatment with melphalan and prednisone supplemented, in cases of anaemia or raised serum creatinine, with vincristine. The prognostic significance for survival was calculated from variables at the time of diagnosis. The major prognostic factors were: age, tumour cell mass assessed by plasma cell percentage in the bone-marrow aspirate and/or M-component concentration, demonstration of Bence-Jones protein, renal function and the haemoglobin and calcium concentrations in the blood. Stage subdivision according the principles established by the Medical Research Council based on haemoglobin concentration and renal function were the best for assessing the prognosis in treated patients. Autopsy was performed on 55 out of the 96 patients who had died. The commonest cause of death was infection (75%).

Parathyroid hormone release from the perfused canine thyroid-parathyroid complex isolated in situ.

A model for direct measurement of hormone release from the canine parathyroid gland is described. The two separate thyroid-parathyroid gland complexes were isolated in situ and perfused independently using a synthetic medium with a welldefined concentration of ionized calcium (Ca++). The concentration of parathyroid hormone (PTH) in the effluent was measured by radioimmunoassay, using an antiserum to bovine PTH that cross-reacts with canine PTH. Displacement curves of dilutions of effluent samples were similar to those of bovine PTH (1-84). During infusion of 1.49 mmol/l Ca++ the PTH release was constant for more than 4 h. Variations in Ca++ from 1.56 to 1.15 or 2.15 mmol/l induced rapid and sustained stimulation or suppression of PTH release. The retained ability of the preparation was ascertained by recording the response to infusion of calcium free medium at the end of each experiment.

B-prolymphocytic leukaemia--a mantle zone lymphoma?

A case of prolymphocytic lymphoma/leukaemia (PL) sensu Galton in a 32-year-old man is presented. The leucocyte count was 19.0 x 10(9)/1 at presentation and tartrate resistent acid phosphatase was present in most prolymphocytes. Immunological investigation of prolymphocytes from lymph nodes, spleen and peripheral blood revealed the surface marker phenotype: SmIg + (mu, (delta), lambda), IgG-Fc-receptor +, C3-receptor +. The prolymphocytes from lymph nodes and spleen were C3-receptor + in a high percentage, while only a few were IgG-Fc-receptor +. This proportion was reversed in the blood prolymphocytes. The histology of lymph nodes was unique and strongly suggested a preferential involvement (homing phenomenon) of the mantle zone of the lymphatic follicle. These results may indicate that emission of prolymphocytes from lymph nodes to circulation involves a change of surface receptors. It is finally suggested to consider the diagnosis of not only hairy-cell leukaemia but also PL in the case of tartrate resistent acid phosphatase-positive lymphoma/leukaemia.