In this multicenter study, 30 patients undergoing matched related or unrelated allogeneic stem-cell transplantation for leukemia were treated with palifermin, and retrospectively compared to a matched control group. Palifermin recipients transplanted with an unrelated donor showed a significant reduction of severity, incidence and duration of oral mucositis WHO grades 2-4. In addition, in the palifermin group the use of opioid analgesics and the duration of total parenteral nutrition decreased, whether stem cells were used from matched related or unrelated donors. No beneficial influence of palifermin on the incidence and severity of acute GVHD (aGVHD) was apparent. The incidence and duration of febrile neutropenia, documented infections, hematopoietic recovery or overall survival remained unchanged. The most common adverse effects included rash or erythema, generally mild and transient in appearance. Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas-regardless of donor status-no effect on the incidence and severity of aGVHD was seen.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in cancer patients receiving myelotoxic chemotherapy. Established risk factors are previous fungal infection, neutropenia exceeding 10 days, older age, active cancer, corticosteroid therapy, administration of broad spectrum antibiotics, allogeneic HSCT, central venous catheter and organ dysfunction. The strategies to manage IFI comprise chemoprophylaxis, preemptive, empirical and directed antifungal therapy. Benefit of antifungal prophylaxis has been proven for fluconazole (400 mg/d) in allogeneic transplant recipients, and for posaconazole (600 mg/d) in patients during AML/MDS induction chemotherapy as well as in patients with GvHD. Pre-emptive therapy based on sensitive diagnostic non-culture methods needs further validation in larger randomized studies before becoming a standard. Empirical antifungal therapy is well established and should consist of either liposomal amphotericin B, itraconazole, voriconazole, or caspofungin. In patients with documented invasive aspergillosis, therapy with voriconazole is the treatment of choice. Liposomal amphotericin B is a good alternative candidate and caspofungin is reserved for salvage treatment. Invasive candidiasis should be treated with caspofungin or one of the lipid based amphotericin B formulations. Since non-albicans species are increasingly observed, the use of fluconazole is reserved for "stable", non-neutropenic patients.

The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD) and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodysplastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other diffi cult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections.

Background: In this ongoing prospective open label study we evaluate the effect of Palifermin on the development of oral and intestinal mucositis in 25 patients undergoing allogeneic or autologous hematopoietic stem cell transplantation (allo/auto-HSCT). Methods: Twenty-five patients, transplanted for acute or chronic leukemia (n=20) and non-Hodgkin’s lymphoma (NHL, n=5) received 60 μg Palifermin per kilogram of body weight per day for three consecutive days before the initiation of conditioning therapy and immediately after HSCT. The control group comprised 9 patients diagnosed with acute leukaemia (n=6) and NHL (n=3). In the Palifermin group the distribution between allo- and auto-HSCT was 16 and 9 compared to 5 and 4 in the control group. Conditioning therapy consisted of fractionated total-body irradiation/Cyclophosphamide in case of leukemia and chemotherapy only based regimens in NHL patients. Oral mucositis was graded daily according to World Health Organisation (WHO) criteria. The intestinal mucosal barrier damage was assessed by analyzing Citrulline serum levels on HSCT days -12, -6, 0, +7, +14 and +21. Results: No severe side effects were observed in our patient cohort. Our preliminary analysis demonstrates a significant decrease in the incidence of oral mucositis WHO grade 3 or 4 with 24 percent in the Palifermin group as opposed to 78 percent in the control group (p=0,013). The median duration of mucositis was 4,7 days (range 0–19) in the Palifermin group compared to 9,3 days (range 0–19) in controls (p=0,037). Whereas 17 evaluable patients in both groups showed a similar decline in Citrulline serum concentrations until day +7 - reflecting a maximal intestinal mucosal barrier injury at this timepoint - a significantly faster recovery of Citrulline levels (18,5 vs 13,8 μM, p=0,04) in Palifermin recipients at day +21 could be found. The use of opioid analgesics as determined by morphine equivalents (median 105mg vs 112mg) was almost equal. However, there was a trend in the duration of total parenteral nutrition (14 vs 18 days, p=ns) in favor of the Palifermin group. Acute graft versus host disease grade I-IV was observed in 29%, grade III-IV in 21% of Palifermin treated patients after an allo-HSCT. Conclusions: Palifermin was generally well tolerated and reduces the incidence and duration of WHO grade 3 and 4 oral mucositis. Further, it promotes a faster recovery of intestinal mucosal damage in allogeneic and autologous HSCT recipients.