The present study compared foscarnet with ganciclovir for preemptive therapy of cytomegalovirus (CMV) infection after allogeneic blood or marrow stem cell transplantation (SCT). Patients with CMV infection, as detected by weekly antigenemia or polymerase chain reaction (PCR) in blood leukocytes, were randomized to intravenous therapy for 2 weeks with either foscarnet at 60 mg/kg or ganciclovir at 5 mg/kg administered every 12 hours; if CMV infection remained detectable, patients received an additional 2 weeks of intravenous foscarnet at 90 mg/kg or ganciclovir at 6 mg/kg given once daily for 5 days per week, after which therapy was stopped. Primary efficacy endpoint was the occurrence of CMV disease or death from any cause within 180 days after SCT. A total of 213 patients were treated with either foscarnet (n ‫؍‬ 110) or ganciclovir (n ‫؍‬ 103). Kaplan-Meier estimates of event-free survival within 180 days after SCT were similar in the 2 treatment groups (P ‫؍‬ .6). During study treatment, severe neutropenia (< 0.5 ؋ 10 9 /L) occurred in 11 (11%) patients on ganciclovir versus 4 (4%) patients on foscarnet (P ‫؍‬ .04), and impaired renal function was observed in 5 (5%) patients on foscarnet versus 2 (2%) patients on ganciclovir (P ‫؍‬ .4). Neutropenia or thrombocytopenia required discontinuation of ganciclovir in 6 (6%) patients but in no foscarnet-treated patient (P ‫؍‬ .03). After allogeneic SCT, preemptive therapy of CMV infection with foscarnet shows similar efficacy as with ganciclovir, but is associated with a lower proportion of patients who develop severe neutropenia and who require discontinuation of antiviral therapy due to hematotoxicity. IntroductionCytomegalovirus (CMV) remains a leading cause of infectious complications after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). In the absence of preventive measures, the incidence of CMV infection is 60% to 70% in the first 3 months after allogeneic SCT when graft donor or patient are pretransplantation CMV seropositive, and one third of patients with evidence of CMV infection develop CMV pneumonia. 1-3 CMV pneumonia is a serious condition, which, with the best presently available therapy, is associated with a high mortality. 4 Therefore, major emphasis must be placed on the prevention of CMV disease in allograft recipients.For CMV-seropositive patients or seronegative patients with a seropositive graft donor, 2 main strategies are currently used to prevent CMV disease in the posttransplantation course. Prophylactic drug treatment is aimed at suppressing CMV reactivation, and is given to all patients irrespective of the results of virologic monitoring. [5][6][7][8] Alternatively, preemptive therapy consists of initiating antiviral treatment only when active CMV infection is documented in order to prevent the development of CMV disease. [9][10][11][12] Thus, with the preemptive therapy approach, the use of potentially toxic drugs against CMV, such as ganciclovir and foscarnet, is restricted to patients at highest risk for CMV ...

In a series of 218 subjects diagnosed as having nonleukemic chronic myeloproliferative disorders in a single institution within a 18-year period, 13 instances of acute transformation were registered. They corresponded to 8 out of 70 patients with idiopathic myelofibrosis (IM), 4 out of 91 with polycythemia vera (PV), and 1 out of 57 with essential thrombocythemia (ET). The actuarial probability of developing such a complication at 100 months from diagnosis reached 20.6% in IM, 8.7% in PV, and 4% in ET. Only 1 IM patient whose condition developed into acute leukemia had received prior cytolytic therapy, whereas, in contrast, all PV and ET patients showing this pattern had previously been treated with either ³²P or alkylating agents. On the other hand, acute transformation in IM generally had an insidious presentation, contrasting with its abrupt onset in most PV and ET patients. Most acute leukemias (12 out of 13) exhibited a myeloid phenotype. The patients’ median survival from diagnosis of the acute transformation was only 3 months, the development of this complication significantly shortening the patients’ overall survival.

In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (