We recently succeeded in eradicating a Fusarium infection by treatment with liposomal amphotericin B (L-AmB). The patient, a 22-year-old man with acute lymphoblastic leukaemia (ALL), developed fever and diffuse cutaneous maculopapular necrotising nodules during post-chemotherapy neutropenia. Fusarium verticilloides was isolated from the skin, and hyphae were observed on direct microscopy. Despite increased WBC and amphotericin B (AmB) treatment (0.7 mg/kg/day for 11 days), he remained febrile and a chest X-ray revealed pulmonary lesions. Fusarium infection was confirmed by bronchial aspirate. AmB was increased to 1 mg/kg/day, and continued for 16 days (total dose 1630 mg). A slight improvement was observed at tomography, but nephrotoxicity developed. Treatment was changed to L-AmB (3 mg/kg/day). The patient received this drug for 20 days (total dose of 3850 mg) with complete regression of the pulmonary lesions. No adverse event occurred, and nephrotoxicity resolved. The patient was discharged from hospital cured of the Fusarium infection and in clinical and haematological remission. No relapse of fusariosis occurred, despite additional courses of intensive chemotherapy. Ambisome could represent an important advance in antifungal treatment since it allows aggressive treatment and eradication of mycoses refractory to conventional therapy while avoiding renal toxicity.

Adult↗

PubMedDate not supplied

Idarubicin in blastic crisis of chronic myelogenous leukemia.

BACKGROUND: Blastic crisis (BC) is the terminal event in the natural history of most chronic myelogenous leukemia (CML) patients. Depletion of the normal stem cell compartment, as well as the proliferative advantage and frequent pharmacoresistance of the blastic clone, contribute to the poor prognosis of CML patients in this phase. Recent clinical trials have shown that idarubicin (IDR) in combination with cytosine arabinoside (ARA-C) is more active than daunorubicin at comparable doses in acute myelogenous leukemia (AML). Furthermore, IDR alone also exhibits antitumoral activity in the BC of CML. METHODS: Twelve Ph+ CML patients in BC (male 8, female 4; median age 45 yrs., range 19-55 yrs.) were treated with IDR 12 mg/m2/die for 3 consecutive days in sequential combination with Ara-C (1 hour i.v. infusion) 120 mg/m2/12 hrs. for 7 consecutive days. BC exhibited a myeloid phenotype in 9 and a lymphoid phenotype in 3 cases. Median duration of the previous chronic phase had been 36 months (range 6-180). RESULTS: Clearing of peripheral and bone marrow blasts was achieved in all but one patient. Three other patients were classified as resistant because of blastic regrowth, and 3 died of infection during postchemotherapeutic aplasia. Two patients achieved complete remission (CR) and 3 partial remission (PR). The median duration of response was 11 months (range 6-32). CONCLUSIONS: In BC of CML the IDR/Ara-C combination led to an encouraging rate of either partial or complete responses. The relatively long duration of unmaintained response was even more interesting, with the duration of PR approaching that of CR. These data suggest that IDR should be considered as one of the first-line drugs in the treatment of BC of CML.

Adult↗

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Ciprofloxacin for infection prophylaxis in granulocytopenic patients with acute leukemia.

Forty consecutive neutropenic patients with acute leukemia receiving oral ciprofloxacin (500 mg twice daily) and ketoconazole (200 mg daily) for selective intestinal decontamination were compared retrospectively with 33 comparable patients treated with polymyxin E (1,500,000 U x 3/day) and nystatin (1,000,000 U x 3/day). The incidence of febrile episodes was slightly lower in ciprofloxacin treated patients (87.5% vs 100%). No gram-negative sepsis was observed in this group compared with seven cases in patients receiving polymyxin E (p less than 0.01). Furthermore, eight patients in ciprofloxacin group (20%) had gram-positive sepsis, compared with five (15.5%) in the polymyxin E group. The incidence of documented fungal infections was similar in the two groups. Ciprofloxacin appears to be an effective agent for the prevention of gram-negative infections in granulocytopenic patients with acute leukemia, but may contribute to a shift in the type of infections in these patients towards those caused by gram-positive microorganisms, intrinsically fairly sensitive or with acquired drug resistance.

Agranulocytosis↗

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[rt-PA in extracardiac thromboembolic vascular occlusions].

Recombinant tissue plasminogen activator (rt-PA) is a thrombolytic agent characterized by elevated but not absolute fibrin specificity. However, its therapeutic dose is high and associated with a variable degree of systemic activation of the fibrinolytic system. Thrombolytic drugs are widely used in acute myocardial infarction and have now begun to be considered for deep vein thrombosis (DVT), pulmonary embolism (PE), and peripheral artery thrombosis (PAT) as well. Although anticoagulant therapy is effective in reducing the immediate complications of venous thromboembolism, thrombolytic therapy has various advantages over anticoagulant therapy, including lysis of thrombi with recanalization of venous circulation, reduction of venous valve damage and prevention of post-phlebitic syndrome. The different dosage regimens of rt-PA recently evaluated (0.71 to 1.76 mg/kg/24 h for 2-4 days) in DVT have caused consistent thrombolysis but also excessive bleeding. The optimal therapeutic range for rt-PA in DVT remains to be determined. Thrombolytic therapy is superior to heparin treatment only in hemodynamically compromised patients with massive PE. The minor systemic fibrinolytic effect and the faster action on thrombi of rt-PA compared with the first generation thrombolytic agents, streptokinase (SK) and urokinase (UK), are very interesting and explain the positive results recently obtained in PE with this drug (50 mg over 2 h, followed, if necessary, by 40-50 mg over 4-5 h) by Goldhaber and Verstraete.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

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1,25-Dihydroxyvitamin D3 in the treatment of idiopathic thrombocythemia and myelofibrosis.

The effect of treatment with 1,25-dihydroxyvitamin D3 administered at the dose of 1.50-3.00 ug/day for at least 12 months was evaluated in three patients with idiopathic myelofibrosis and in five patients with idiopathic thrombocythemia. This treatment did not cause any significant change in the hematological values or the clinical course of the myeloproliferative diseases in any of the patients. Based on these data, treatment with 1,25-dihydroxyvitamin D3 in non toxic doses seems to be of doubtful benefit in patients with these disorders.

Adult↗