Results of combination therapy with amifostine, pentoxifylline, ciprofloxacin and dexamethasone in patients with myelodysplastic syndrome and acute myeloid leukemia.

Myelodysplastic syndrome (MDS) is a clonal disease of the bone marrow characterized by abnormal hematopoiesis and cytopenias. It has been shown that abnormal cytokine production together with apoptosis are major contributors to the cytopenias associated with the disorder. As the interaction of cytokines plays a role in the pathogenesis, suppression of the cytokine production by the administration of the combination of pentoxifylline, ciprofloxacin, and dexamethasone (PCD combination) has resulted in the correction of at least some aspects of the cytopenias in the majority of patients and in complete hematologic remission in a small percentage. The aminothiol prodrug amifostine, a compound to protect tissues from cytotoxic drugs and radiotherapy has been found to stimulate proliferation of normal hematopoiesis and suppress apoptosis in patients with MDS. In this study we report the results of combination therapy of amifostine and PCD in 12 patients with MDS and acute myeloid leukemia (AML). Amifostine was given in a dose of 200 mg/m(2), as an i.v. infusion administered in 10 min, three times a week; pentoxifylline 2400 mg/day, (3 x 800 mg) p.o.; ciprofloxacin, 1 g/day p.o.; dexamethasone 4.5 mg/day p.o. We achieved 66% response rate in our patients. In some cases responses were achieved in only thrombocytopenia or anemia whereas in others responses were achieved in multiple series. As a result it was found that amifostine + PCD combination may be beneficial in reversing cytopenias in the treatment of MDS and AML and is worth further study.

Hyperbaric oxygen therapy does not potentiate doxorubicin-induced cardiotoxicity in rats.

The current use of doxorubicin is regarded as an absolute contraindication for hyperbaric oxygen (HBO2) therapy because of the increased risk of cardiotoxicity. The aim of this study was to investigate whether additional exposure to HBO2 during the course of doxorubicin treatment would further increase the cardiotoxicity of doxorubicin in rats. Female Wistar rats were treated with either HBO2 (n = 10) or doxorubicin (n = 8) or a combination of both treatments (n = 10) for 4 consecutive weeks and followed up for an additional 4 weeks. Cardiomyopathy was evaluated using two-dimensional and M-mode echocardiography at baseline, at the fourth, sixth and eighth weeks, and by histopathological investigation of the rat hearts at the eighth week. Doxorubicin treatment significantly reduced ejection fraction and fractional shortening (P < 0.001) and caused severe histopathological injury (P < 0.05) indicating development of cardiotoxicity. Although the combination of doxorubicin and HBO(2) also markedly reduced ejection fraction and fractional shortening (P < 0.001), this reduction was significantly less than that of doxorubicin treatment (P < 0.05). HBO2 therapy also attenuated doxorubicin-induced histopathological changes in rat hearts (P < 0.05). HBO2 alone did not alter echocardiographic parameters or histopathological findings (P > 0.05). In conclusion, HBO2 therapy does not potentiate doxorubicin-induced cardiotoxicity in rats. Cardioprotection conferred by HBO2 against doxorubicin warrants further investigation.