Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients with hematologic malignancies developing a filamentous fungi infection (FFI) and to define the prognostic factors for their outcome. DESIGN AND METHODS: A retrospective study, conducted on patients admitted to 14 Hematology divisions of tertiary care or university hospitals, participating in the GIMEMA Infection Program, over a ten-year period (1988-1997). The study included patients with hematological malignancies and a histologically and/or microbiologically proven or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12 myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who developed a proven FFI. Eighty percent of the patients had been neutropenic for an average of 14 days before the infection, and 71% had an absolute neutrophil count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of infection were: lungs (85%), nose and paranasal sinus (10%), and other sites (5%). The diagnosis was made while still alive in 310 patients (79%), and at autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of patients with pulmonary FFI, while computed tomography (CT) scan of the thorax was positive in 95% of cases. A significant diagnostic advantage for CT scan was observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was identified as the cause of FFI in 296 patients, Mucorales in 45 patients, Fusarium in 6 patients and other filamentous fungi species in 4 patients, while in a further 40 patients no agent was identifiable. The overall mortality rate three months after the diagnosis of FFI was 74%, and fungal infection had been the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our retrospective study shows that FFI still remains a life-threatening complication in neutropenic patients. Despite appropriate treatment, half of the patients die due to this complication. The use of glucocorticoids and recovery from neutropenia are the most important prognostic factors. Mucorales infections are associated with a significantly poorer prognosis than those due to Aspergillus spp

Recombinant alpha interferon in the treatment of low-grade non-Hodgkin's lymphoma: results of a cooperative phase II trial in 31 patients.

Thirty-one patients with advanced stage of favorable histology non-Hodgkin's lymphomas were entered into a multicenter phase II trial with recombinant alpha A interferon as single agent. Interferon was administered intramuscular in doses of 6 x 10(6)/IU/m2 three times per week for 12 weeks. Dose escalation was applied, in the absence of toxicities greater than WHO grade II, in patients not responding after 4 weeks. In responding patients treatment was continued at the same dose with a weekly maintenance schedule for 12 additional weeks. Objective responses (4 complete, 10 partial) were obtained in 14 of the 27 evaluable patients (52%). Median time to progression was 15 months for partial responders, while none of the complete responders has relapsed up to the present time. Toxicity was generally moderate and manageable. Treatment was discontinued in three patients because of side effects, and one patient refused therapy after 3 weeks. Our study shows that recombinant alpha A interferon has antitumor activity in patients with favorable histology non-Hodgkin's lymphoma

Standard- versus high-dose lenograstim in adults with hematologic malignancies for peripheral blood progenitor cell mobilization.

BACKGROUND: The aim of this retrospective, multi-center study was to compare high- versus standard-dose lenograstim after chemotherapy in collecting target dose of CD34+ peripheral blood progenitor cells (PBPCs) in adult candidates for autologous transplant STUDY DESIGN AND METHODS: A total of 166 consecutive patients (28 acute leukemias [ALs], 77 lymphomas, 61 multiple myeloma [MM]) underwent 182 mobilization procedures Only the first were analyzed The CD34+ cell target was at least 2 x 10(6), 4 x 10(6), and 8 x 10(6)/kg and lenograstim started on days +19, +1, and +5 from the end of chemotherapy for AL, lymphomas, and MM, respectively Eighty-seven and 79 patients, respectively, received 5 and 10 mu g/kg/day lenograstim subcutaneously (sc) An analysis to evaluate factors predicting satisfactory procedures and outcome of transplants performed with first-mobilization-procedure PBPCs was conducted Most patients received 6 mg of pegfilgrastim or 5 mu g/kg/day lenograstim sc after transplant RESULTS: In multivariate analysis, high-dose lenograstim (p = 0 053) in MM and male sex (p = 0 028) were positive predictive factors for reaching cell target Fludarabine negatively influenced stimulation length (p = 0 002). Apheresis, CD34+ cells mobilized and collected, blood volume processed, side effects, transplants performed, and engraftment time were similar between lenograstim cohorts. Pegfilgrastim versus lenograstim delayed platelet (PLT) recovery times (13 days vs 11 days, p = 0 036) CONCLUSIONS: High-dose lenograstim more efficiently mobilized MM patients requiring the highest PBPC target but did not influence transplants performed and engraftment time Male patients mobilized more efficiently Fludarabine negatively influenced stimulation length Finally, pegfilgrastim seems to delay PLT recover

Localization of aspergillosis to the central nervous system among patients with acute leukemia: Report of 14 cases

We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i.e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without CNS localization

TRAIL decoy receptors mediate resistance of acute myeloid leukemia cells to TRAIL

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a potential anticancer agent. However, many cancer cells are resistant to apoptosis induction by TRAIL. The present study was designed to evaluate the sensitivity to TRAIL-induced apoptosis in acute myeloblastic leukemias (AML)

Localization of aspergillosis to the central nervous system among patients with acute leukemia: Report of 14 cases

We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i.e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without CNS localization