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.

Superiority of high-dose platinum (cisplatin and carboplatin) compared to carboplatin alone in combination chemotherapy for small-cell lung carcinoma: a prospective randomised trial of 280 consecutive patients.

PURPOSE: A prospective randomized trial in small-cell lung cancer (SCLC) was performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields higher response rates and survival, than carboplatin alone in a combination chemotherapy regimen. PATIENTS AND METHODS: Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by stage of disease, LDH and performance status. The treatment was in arm A: three courses induction chemotherapy with carboplatin (AUC = 4, day 1), cisplatin (35 mg/m2, days 2 and 3), teniposide (50 mg/m2, day 1-5), vincristine (1.3 mg/m2, day 1) every four weeks, followed by cyclophosphamide (3 g/m2, day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m2, day 112), and finally one course cisplatin, carboplatin, teniposide and vincristine, (days 140-144). Arm B also comprised a total of six courses, identical to those in arm A except for omission of cisplatin. RESULTS: There were no significant differences in the overall treatment outcome for A vs. B, in terms of response rates (72% in both arms), complete response rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both the CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0.05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in the high-dose platinum arm compared to the carboplatin alone arm. CONCLUSIONS: The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.

Cobalamin binding proteins in patients with HIV infection.

P-Cobalamins have been reported to be decreased in patients with HIV infection. Because of this, we found it of interest to examine both cobalamin-saturated binding proteins (holo-transcobalamin, holo-TC and holo-haptocorrin, holo-HC) and cobalamin unsaturated binding proteins (apo-transcobalamin, apo-TC and apo-haptocorrin, apo-HC). The results are given as range and (median). Eighteen male HIV-infected patients with plasma cobalamins below 200 pmol/l were studied. We found low concentrations of holo-TC (37-88 (47.5) pmol/l) and holo-HC (64-184 (135.5) pmol/l). The concentration of apo-TC and apo-HC was increased (480-1730 (1025) pmol/l; 70-800 (235) pmol/l). It is concluded that, in HIV-infected patients, low plasma cobalamin does not reflect a low concentration of transcobalamin or haptocorrin. In 20 HIV-infected patients and 31 patients with malignant haematological diseases, the TC isopeptide patterns were determined. In the HIV group, an increased frequency of TC isopeptide X was found and the overall distribution of TC isopeptides was significantly different from the reference population (p less than 0.05). There was no difference between the group of patients with malignant haematological diseases and the reference group.

[The risk of ornithosis among the staff of Copenhagen Zoo]. / Ornitoserisiko hos ansatte i Københavns Zoologiske Have.

Because a keeper in Copenhagen ZOO had developed ornithosis, clinical and serological examination of the staff of the ZOO was instituted. The object was to demonstrate any possible threatening epidemic and also to demonstrate if the staff of the ZOO were particularly exposed to the risk of ornithosis. Neither of these could be confirmed.

Serum thymidine kinase--a marker of bone marrow toxicity during treatment with zidovudine.

Serum thymidine kinase (S-TK) was measured weekly in 16 randomly selected patients with AIDS or AIDS-related complex (ARC; Centers for Disease Control group IV A or group IV C-2) who participated in a controlled study of the efficacy of zidovudine therapy. S-TK increased significantly (P less than 0.01) in the zidovudine group, whereas it remained stable in the placebo (control) group. On the basis of this observation, the value of S-TK measurements as a predictor of bone marrow toxicity during zidovudine therapy was investigated in 42 patients with AIDS or ARC who received zidovudine as part of their usual treatment. There was a significant association between S-TK, haemoglobin and neutrophil counts measured after the first 4 weeks of therapy and the risk of developing bone marrow toxicity during the following 6 months. Combined, measurements of S-TK and neutrophil counts seem to be well suited for the identification of patients who have a high probability for developing bone marrow toxicity during zidovudine treatment.

Plasma histidine-rich glycoprotein and plasminogen in patients with liver disease.

Histidine-rich glycoprotein (HRG) has been reported to be a fibrinolysis regulating protein due to its capacity to bind to the high affinity lysine binding sites of plasminogen. Using immunological methods we have measured the concentrations in plasma of HRG and total plasminogen and calculated the amounts of plasminogen not bound to HRG (free plasminogen) in 28 patients with moderate to severe liver disease. All three parametres showed wide individual variations, but with decreasing functional capacity of the liver the individual levels of plasminogen were reduced earlier than those of HRG leading to decreased amounts of free plasminogen. Simultaneous determinations of HRG and total plasminogen combined with a calculation of free plasminogen might yield valuable information when evaluating patients for the availability of plasminogen.

Platelet aggregation and release of ATP in patients with hepatic cirrhosis.

The purpose of this study was to assess the platelet aggregation and releasable platelet ATP in patients with alcoholic cirrhosis (n = 10) and primary biliary cirrhosis (n = 10). In patients with liver disease a significant decrease was found in both adenosine diphosphate-induced aggregation (P less than 0.01) and collagen-induced aggregation (P less than 0.001) compared with that of controls, but there was no significant difference between the two groups of patients. Patients with primary biliary cirrhosis release smaller amounts of ATP than patients with alcoholic cirrhosis, and compared with the controls there was a significant (P less than 0.001) decrease in the releasable ATP in the patient groups. These results suggest that platelets are damaged during an intravascular activation (loss of granules), which gives rise to their subsequent hypo-function when tested in vitro.

Decreased blood platelet volume and count in patients with liver disease.

Mean platelet volume (MPV) and count (PLT) were assessed in patients with moderately affected liver function. PLT was significantly decreased in patients with liver disease (197 X 10(9)l-1 +/- 87 (SD), no. = 79) compared with that of controls (273 X 10(9)l-1 +/- 53 (SD), no. = 37, P less than 0.001). MPV in patients with liver disease (9.25 +/- 1.14 fl) was significantly lower than that of controls (10.52 +/-0.74 fl, P less than 0.001). In control subjects MPV and PLT were inversely correlated (r = -0.48, P less than 0.01), but statistical significance was not found in patients with liver disease (r = -0.2, 0.05 less than P less than 0.1). It is concluded that the low MPV and PLT are compatible with an intravascular activation (loss of granules) and increased consumption of platelets, which may take place in the diseased liver even in patients with a relatively well preserved liver function.

Prediction of spleen size by routine radioisotope scintigraphy.

Technetium-99m scintigraphy of the spleen was performed in 32 patients with various haematologic disorders prior to splenectomy. From the gamma camera image of the spleen, the weight of the spleen was estimated using two different mathematical formulas, and the results obtained were compared to the postoperative spleen weight. Both formulas revealed spleen weights showing highly significant correlations to the postoperative spleen weight and with similar standard deviations. Visual evaluation of the scintigram by an experienced examiner with classification of the spleens into four groups according to spleen weight revealed results as good as the mathematical calculations in predicting the postoperative spleen weight, both techniques giving diagnostic specificities of 0.70-0.80 for all groups and diagnostic sensitivities of 0.80-1.00. Physical examination of the abdomen showed that about 50% of the spleens weighing between 250 and 1,000 g were not palpable. Therefore, it is concluded that physical examination of the abdomen alone is unreliable. Radioisotope scintigraphy of the spleen is recommended, this method being fast, with negligible discomfort to the patient, and with sufficient accuracy for daily clinical work.

Antithrombin III and platelets during the normal menstrual cycle and in women receiving oral contraceptives low in oestrogen.

Determinations of platelet number and concentration of antithrombin III (AT-III) were made in samples of plasma collected during one normal or hormone-simulated cycle in 14 young, normal women and in 11 women using an oral contraceptive low in oestrogen. Distinct, individual levels caused the variation of both parameters to be greater within the group than individually. Despite a few exceptions, a slight but statistically significant increase in the platelet number and AT-III level occurred around midcycle in the normal group. In the hormone group the platelet number increased slightly in the treatment period, while the AT-III level showed a corresponding slight decrease. The large decreases in AT-III levels reported by other authors testing oral contraceptives high in oestrogen were not seen in our study.

Bone mineral content in myelomatosis.

Bone mineral content (BMC) was determined by photon absorptiometry on both forearms in 28 patients with myelomatosis. Nineteen patients had received intermittent treatment with cytostatic agents and prednisone. No significant reduction of BMC was found between the patients with myelomatosis and an age- and sex-matched normal population. Neither was any significant decrease in BMC with the duration of the disease demonstrated. In 16 patients, routine X-ray indicated osteoporosis, but their BMC was not reduced compared to the patients without osteoporosis on X-ray. However, the former patients were significantly older than the latter. Provided the term "generalized osteoporosis" implies reduced mineral content in all bones, the study indicates that patients with myelomatosis have not generalized osteoporosis.

Variable interpretation of liver scintigraphy in malignancy as an aid in clinical decision-making.

Despite technical progress in liver radioisotope scintigraphy, the overall accuracy in detecting metastases has not improved. It has been suggested that a fixed scintigram interpretation in reply to changing clinical problems is partly responsible. An evaluation of the possibilities of improving the clinical value of the test by using six cutoff levels in the scintigraphic interpretation is presented. The test population is a prospectively planned consecutive series of 185 patients strongly suspected of having gastric or colo-rectal malignancies. The incidence of liver metastases was 15%. The relationship between the predictive value of a positive test and the false negative ratio at different incidences of metastases is demonstrated graphically. To improve the clinical value of liver scintigraphy, a close cooperation between clinicians and physicians in nuclear medicine to define the clinical problem and the appropriate scintigraphic cutoff level is necessary.