Amphotericin B lipid complex for the treatment of patients with acute leukemia and hepatosplenic candidiasis.

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.

Hepatosplenic candidiasis in patients with acute leukaemia.

A retrospective study of 23 patients with acute leukaemia and hepatosplenic candidiasis (HSC) was conducted to evaluate clinical treatment characteristics in terms of amount and duration of antifungal agents and to assess treatment outcome. Patients were admitted to two major tertiary care centres between 1990 and 1998. The diagnosis of HSC was based on clinical, blood cultures, histologic and imaging studies. Patients were treated with amphotericin B without interruption of the planned chemotherapy regimens. Serial magnetic resonance imaging (MRI) studies were the main tool for following patients' response and activity of the fungal lesions in conjunction with clinical and laboratory parameters. Treatment with amphotericin B was continued until resolution of all clinical symptoms and signs attributable to HSC, obtaining negative blood cultures and the appearance of at least healed lesions on MRI. Amphotericin B was discontinued in four patients because of severe nephrotoxicity (two patients), or continuous fever and persistent fungal lesions on MRI (two patients). Amphotericin B lipid complex (ABELCET) was successfully used as salvage therapy for these refractory patients. Four patients died with evidence of HSC despite treatment and supportive measures. The response rate for treatment of HSC was 82%. The mean total dose of amphotericin B including empirical treatment was 4 g and the median duration of treatment for responding patients was 112 d. The median number of days of anti- fungal treatment before the disappearance of fever was 19 d. Our results confirmed the need for protracted courses of antifungal agents for the successful eradication of HSC. Chemotherapy for the underlying disorder should not be interrupted or delayed in order to treat HSC.

The role of 2-chlorodeoxyadenosine in the treatment of patients with refractory angioimmunoblastic lymphadenopathy with dysproteinemia.

Treatment of patients with angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) often constitutes a challenge for the clinical haematologist. Single-agent and combination chemotherapy have failed to increase the response rate or survival of patients with AILD. A total of seven patients with refractory or relapsed AILD were treated with 2-chlorodeoxyadenosine (2-CdA) for variable number of cycles. The overall response rate was 57% with two patients (28.5%) achieving complete and sustained response. 2-Chlorodeoxyadenosine appears to be an active agent for patients with previously treated AILD. Phase II studies evaluating the efficacy of this agent as front-line treatment for AILD are justified, especially in the absence of any effective therapy for this disorder.

Diagnosis and monitoring response to treatment of hepatosplenic candidiasis in patients with acute leukemia using magnetic resonance imaging.

Hepatosplenic candidiasis (HSC) is a morbid complication encountered in immunocompromised individuals, especially, those being treated with intensive chemotherapy protocols for acute leukemia. Immediate recognition of this complication and initiation of appropriate treatment is crucial in order to control the infection, decrease the morbidity and mortality, and avoid delays in treatment of the underlying condition. The definitive diagnosis requires either positive blood cultures for yeasts in the presence of abnormal findings on imaging studies consistent with HSC, or liver biopsy demonstrating yeast forms or pseudohyphae. We describe our experience in the evaluation of 15 patients with HSC using magnetic resonance imaging (MRI) as a diagnostic and follow-up tool. The diagnosis of HSC was established by liver biopsy in 11 patients (73%), and by positive blood cultures for Candida in 4 patients (27%). All patients had MRI findings consistent with HSC during the study period. Amphotericin B was administered intravenously to all 15 patients (median duration of treatment, 62 days). Repeat MR images were obtained at 2 weeks, 6 weeks and then at monthly intervals until the resolution of abnormalities. The median time for the disappearance of MRI lesions was 9 weeks. Alterations in the appearance of lesions on MRI were noted throughout chemotherapy in all the 13 (86.6%) responding patients. Our results suggest that MRI when used in patients with high clinical suspicion for HSC provide an alternative for liver biopsy or other invasive diagnostic procedures and that appropriate response to treatment can be safely monitored by obtaining sequential MRI studies.