Summary:We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P ¼ 0.02). Also grade III or IV infections (P ¼ 0.008), duration of antibiotic therapy (P ¼ 0.03) and duration of fever (P ¼ 0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation. Am.

The incidence of prostate cancer (PC) is increasing steadily with the aging population in Singapore. As the pattern of chromosomal aberrations in Asian men with PC is poorly understood, we investigated the numerical aberrations for chromosomes 7, 8, 11, and 17 by fluorescence in situ hybridization (FISH). FISH was performed on standard sections and tissue microarrays of 54 PC and 33 benign prostatic hyperplasia (BPH) specimens. Among the 54 PC specimens, FISH detected 44 cases as aneusomy and two as disomy and was unsuccessful for eight cases. Cytogenetic alterations of two or more chromosomes per tumor were detected in 33/46 (72%) PCs. The most frequent alteration was aneusomy of chromosome 8 detected in 34/46 (74%) cases followed by numerical aberrations in chromosome 7 (61%). Gain of 8q24, loss of chromosome 7, and gain of 11q13 were associated with higher Gleason score and were statistically significant. Gain of chromosome 7 was more common in locally advanced disease, while gain of chromosome 11q13 and chromosome 7 was more common in metastatic disease.

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