Remission Induction Chemotherapy For Acute Leukemia Research Articles

Real-life comparison of posaconazole versus fluconazole for primary antifungal prophylaxis during remission-induction chemotherapy for acute leukemia

Patients undergoing remission-induction intensive chemotherapy for acute leukemia are at high risk for life-threatening invasive fungal infections (IFIs). Primary antifungal prophylaxis with posaconazole has been shown to reduce the incidence of IFI compared to fluconazole, but real-life data are limited and the effect on mortality remains unclear. This retrospective cohort study compared fluconazole and posaconazole as primary prophylaxis in real-life practice over a 10-year period, in a Canadian hospital. A total of 299 episodes were included (fluconazole, n = 98; posaconazole, n = 201), of which 68% were first inductions. The underlying hematologic malignancy was acute myeloid leukemia or myelodysplastic syndrome in 88% of episodes and acute lymphoblastic leukemia in 9%. Overall, 20 cases of IFI occurred (aspergillosis, n = 17; candidiasis, n = 3) and 14 were considered as breakthrough IFI. IFI incidence was significantly lower in the posaconazole group (3.5% versus 13.2%; p = 0.001). Empirical or targeted antifungal therapy was also reduced in the posaconazole cohort. Mortality was similar in both groups. In a real-life setting in Canada, primary posaconazole prophylaxis reduces the incidence of IFI during remission-induction chemotherapy, compared to fluconazole.

Candidemia in Cancer Patients: Focus Mainly on Hematological Malignancyand Hematopoietic Stem Cell Transplantation.

Although many new antifungals have become commercially available since 2000, candidemia remains an important public health issue because of its poor prognosis. Some studies have suggested that early antifungal therapy is associated with decreased mortality; however, it is difficult to promptly diagnose candidemia because of the poor sensitivity of blood cultures. Thus, prophylaxis against Candida infection is recommended in patient groups in whom the risk of infection is high, such as allogeneic hematopoietic stem cell transplant recipients or those undergoing intensive remission-induction chemotherapy for acute leukemia. Non-Candida albicans candidemia is dominant among hematology patients, and the use of an echinocandin is recommended as the initial therapy. However, echinocandin-resistant Candida have been reported with increasing frequency, mainly in Candida glabrata. Several studies have reported that echinocandin resistance is associated with prior exposure to an echinocandin. Therefore, susceptibility testing is vital in treating severe or refractory candidemia, and the introduction of an antifungal stewardship program is recommended.

Incidence of invasive aspergillosis following remission-induction chemotherapy for acute leukemia: a retrospective cohort study in a single Canadian tertiary care centre.

The decision to use universal primary antimould prophylaxis to prevent invasive aspergillosis in patients with acute leukemia depends on the incidence of infection at individual centres. We determined our institution's incidence of invasive aspergillosis among patients who received remission-induction chemotherapy for acute leukemia to evaluate the potential benefits of primary antimould prophylaxis. We conducted this retrospective cohort study at a Canadian tertiary care centre. From the central pharmacy registries, we retrieved records for all adult patients for whom remission-induction chemotherapy for acute leukemia was prescribed between 2008 and 2010. We retrieved clinical, microbiologic, pathologic and radiologic data from the patients' medical charts. The primary outcome was a diagnosis of probable or proven invasive aspergillosis up to 180 days after resolution of aplasia. We retrieved records for 123patients with acute leukemia. Twenty-two of these patients did not receive the prescribed chemotherapy and were excluded from the analysis. Of the 101patients included, 77 (76.2%) had acute myeloid leukemia. Overall, 136courses of chemotherapy were administered, with more than 1 course administered to 26 (25.7%) of the 101patients. In 9 of the patients (8.9%; 95%confidence interval 4.2%-16.2%), invasive aspergillosis was diagnosed (3proven and 6probable cases) a median of 19 (range 11-34) days after initiation of chemotherapy. In 7 (78%) of these 9patients, invasive aspergillosis occurred during the first course of chemotherapy. Three patients died within the first year after diagnosis of invasive aspergillosis. We found a high incidence (8.9%) of invasive aspergillosis at our centre. This finding triggered the introduction of targeted antimould prophylaxis for patients with acute leukemia who were undergoing remission-induction chemotherapy.