Non-pegylated liposomal doxorubicin (Myocet®) in patients with poor-risk aggressive B-cell non-Hodgkin lymphoma.

The incidence of non-Hodgkin lymphomas increases with age. Non-pegylated liposomal formulations of doxorubicin (Myocet®) reduce systemic and cardiac toxicity especially in the elderly, who often have cardiac diseases. We treated 80 patients (mean age 70.9 years) with poor-risk diffuse large B-cell lymphoma with the R-COMP 21 regimen (Myocet® 50 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2), rituximab 375 mg/m(2), prednisone 100 mg/day). In all, 82.5% and 13.7% patients showed complete and partial responses, respectively. Sixty-two of the 80 patients are alive and disease-free (77.5%), while 3/80 are alive with active disease and 15 patients (18.7%) have died (median follow-up: 31 months). The estimated probability of overall survival at 12/24 months from admission was 93.5/87.3%, respectively. There were no therapy-related cardiac events and the ejection fraction improved (from 51.6 ±â€Š6.9% to 54.2 ±â€Š3.9%). Grade 3-4 neutropenia occurred in 22% of patients. We concluded that Myocet® shows both efficacy and tolerability, mainly at the cardiac level.

Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal failure. A synergistic effect with r-HuEpo.

BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This effect may be related to the suppression of iPTH release, or to a direct effect on erythropoiesis. METHODS: Thirty-three patients with chronic renal failure were enrolled; among them, 24 were on chronic hemodialysis and 9 on conservative management. None had other chronic or hematological disease, aluminum levels were below 20 microg/l and DFO testing was negative. The iPTH range was 250-480 pg/l. None were treated with C or r-HuEpo. In vitro study: Samples were drawn for a basal erythroid precursor (burst forming unit-erythroid BFU-E) study: Mononuclear cells were incubated for 14 days with r-HuEpo 3U/ml (A), r-HuEpo 3U/l + C 30 pg (B), r-HuEpo 3U/ml + C 300 pg (C), or r-HuEpo 30 U/ml + C 300 pg (D). In vivo study: After the basal evaluation, 10 patients on chronic dialysis were treated with C (Calcijex-Abbott) 1 microg three times a week, and 4 patients served as controls. BFU-E studies were performed after 1, 2 and 4 months. RESULTS: In vitro, culture B showed increased BFU-E proliferation vs. A (41 +/- 23 vs. 27 +/- 15, p < 0.02); in cultures C and D, proliferation was 61 +/- 31 and 78 +/- 42, respectively, p < 0.01 vs. A. There was no difference among patients with predialysis renal failure and those on dialysis. BFU-E proliferation was inversely related to basal Hb (p < 0.04) and CRP levels (p < 0.05). During the in vivo study, all cultures showed a progressive increase in proliferation without a plateau level (basal, after 1, 2 and 4 months, respectively) In A: 17 +/- 8, 22 +/- 13, 30.9 +/- 14.9, 41.4 +/- 20; in B: 27.3 +/- 15, 35.6 +/- 20, 45.5 +/- 21, 57 +/- 26; in C: 48.2 +/- 20.6, 63.7 +/- 32, 75.7 +/- 37, 83 +/- 40; in D: 72 +/- 24, 91 +/- 42, 106 +/- 42, 110 +/- 42.3 (all p < 0.001). Hb and Hct showed a significant increase (p < 0.03) in the treatment group. The decrease in iPTH was not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia, C has a direct effect on erythroid precursors proliferation, as demonstrated both in vitro and in vivo, with a synergistic effect with r-HuEpo. C may be a useful adjuvant therapy to r-HuEpo treatment.