amphotericin-b and Lymphoproliferative-Disorders

To assess the clinical and economic benefit of low-dose (50 microg/m2) filgrastim after peripheral blood stem-cell transplantation (PBSCT) in a randomized, placebo-controlled double-blinded study.. Thirty-eight patients with lymphoproliferative disorders were randomized to receive low-dose filgrastim (19 patients) or placebo (19 patients) beginning on the first day after stem-cell reinfusion and continuing until absolute neutrophil count (ANC) was greater than 0.5 x 10(9)/L. All patients received greater than 2.5 x 10(6) CD34+ cells/kg, which was mobilized with chemotherapy and filgrastim 300 microg from the fifth day. An economic analysis was performed based on the outcome in the two groups.. Neutrophil engraftment was significantly more rapid in patients who received filgrastim with a median number of days until ANC was greater that 0.5 x 10(9)/L of 10 (9 to 13) versus 14 (9 to 19; P < .0001). The time to reach an ANC greater than 1 x 109/L was 12 (9 to 14) versus 16 days (10 to 25; P < .0001). The total number of patients who required intravenous antibiotic therapy was lower in the filgrastim-treated group (68%) compared with the placebo group (89%); also, the median number of days with fever and the duration of antibiotic therapy were shorter, although these differences did not reach statistical significance. However, although only three of 19 (16%) patients who received filgrastim required amphotericin, 11 of 19 (58%) who received placebo did require it, and amphotericin usage was significantly less in the filgrastim group (P = .029). Finally, in-patient stay was significantly shortened in those who received filgrastim from 16 (13 to 23) to 13 days (11 to 18; P = .0003).. Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs, which makes it economically viable for patients who are undergoing high-dose chemotherapy.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Cost-Benefit Analysis; Double-Blind Method; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Length of Stay; Lymphoproliferative Disorders; Male; Middle Aged; Neutropenia; Neutrophils; Recombinant Proteins; Transplantation, Autologous; Treatment Outcome

Bloodstream infection with non-Candida albicans Candida species is one of the serious complications among patients with hematological malignancies who receive long-term prophylactic antifungal agents. Here we describe three cases of Candida fermentati (C. fermentati) candidemia after allogeneic stem cell transplantation for hematological malignancies. Case 1 is fluconazole-breakthrough C. fermentati fungemia, which was well controlled with liposomal amphotericin B. Case 2 and 3 were caspofungin-breakthrough C. fermentati fungemia. In case 2, blood culture turned negative for Candida responding to liposomal amphotericin B. Although in vitro susceptibility data for the isolated pathogen suggested the efficacy of both caspofungin and liposomal amphotericin B in all three cases, clinically liposomal amphotericin B seemed to have been more effective for eradication of the pathogen from blood stream. C. fermentati needs to be considered as a possible cause for breakthrough candidemia among post-transplant patients with prolonged antifungal prophylaxis. Discrepancy between in vitro and in vivo susceptibility to antifungals, especially to echinocandins, might provide a clue for the optimal choice of antifungals for C. fermentati infections.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidemia; Caspofungin; DNA, Ribosomal; Echinocandins; Fatal Outcome; Female; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Lymphoproliferative Disorders; Male; Middle Aged; Sequence Analysis, DNA

Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N = 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for ≥ 8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (< 8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P = 0.027) and proven/probable IFIs (P = 0.012). At multivariate analysis prolonged aero-d-AmB administration retained an independent protective effect on airways IFIs (P = 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P=0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

Topics: Adolescent; Adult; Aerosols; Aged; Amphotericin B; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Combinations; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Incidence; Italy; Lymphoproliferative Disorders; Male; Middle Aged; Mycoses; Respiratory System; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Transplantation, Homologous; Young Adult

Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation.

Topics: Adult; Amphotericin B; Antibodies, Monoclonal, Murine-Derived; Antiprotozoal Agents; Antiviral Agents; Epstein-Barr Virus Infections; Ganciclovir; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leishmaniasis, Visceral; Lymphoproliferative Disorders; Male; Meglumine; Meglumine Antimoniate; Opportunistic Infections; Organometallic Compounds; Postoperative Complications; Remission Induction; Rituximab; Sirolimus

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brain; Brain Diseases; HIV Infections; Humans; Liposomes; Lymphoproliferative Disorders; Magnetic Resonance Imaging; Male; Middle Aged; Mucormycosis; Radiography; Sphenoid Sinus; Sphenoid Sinusitis; Treatment Outcome

We sought to assess if leaving in place a previously inserted noncolonized or infected implantable catheter (IC) is associated with an increase in morbidity in patients undergoing autologous peripheral stem cell transplantation (APSCT). Medical records from all patients between March 1997 and January 2002 undergoing APSCT with an IC in place were reviewed. Case group (IC in place) was compared with a control group (no IC) from 6 days prior to 60 days after APSCT. In all, 43 cases were matched with 43 controls by underlying disease, age and sex. In both groups, duration of neutropenia and use of antimicrobial prophylaxis were comparable. Underlying malignancies were lymphoma (22/24), multiple myeloma (14/12), leukemia (3/3), and others (7/7) in case and control groups. Cases and controls had comparable rates of risk for fever, bloodstream infection, use of vancomycin and amphotericin B, and death, as well as comparable lengths of stay and readmissions. ICs were used in 20 of 43 patients. Using the IC did not significantly increase the risk of fever, bloodstream infection, length of stay, and/or readmissions after APSCT but was associated with increased use of antibacterial and antifungal agents. Leaving in place a previously inserted, noncolonized or infected IC did not increase morbidity in patients undergoing APSCT.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Retrospective Studies; Transplantation, Autologous; Vancomycin

A group of 31 oncohaemopathic patients (17 male, mean age 44 +/- 6 years), diagnosed as having primary deep fungal infection involving the lungs, were retrospectively evaluated. When infection was suspected on a clinical basis the major associated risks for death were the duration of bone marrow aplasia (12 +/- 7 versus 21 +/- 6 days, P < 0.001), increase in white blood cells and, in particular, prolonged granulocytopenia (11 +/- 5 versus 24 +/- 8 days, P < 0.001) when survivors were compared with patients, who died. Our therapeutic empirical approach was based on the association of i.v. amphotericin B, 1 mg kg-1 day-1, with oral 5-fluorocytosine (5-FC) 150 mg kg-1 day-1. Only 9 subjects received combination therapy for more than 7 days. For majority of them, oral 5-FC was interrupted because of altered compliance or sustained liver damage. A chi 2 test for independent parameters showed (P = 0.0021) a concentration of deaths among patients who received amphotericin B alone (15/22); none of the patients treated with amphotericin B + 5-FC (9 cases) died. Results generally suggest that a more favourable outcome was statistically associated with empirical antifungal combination therapy in deep fungal infection, although both treatment regimens showed effectiveness in terms of survival. Nevertheless the low 5-FC compliance and the small sample do not indicate the safe use of this drug in a large population.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; Cryptococcus; Drug Therapy, Combination; Female; Flucytosine; Humans; Lung Diseases, Fungal; Lymphoproliferative Disorders; Male; Middle Aged; Mycoses; Prognosis; Retrospective Studies; Risk Factors; Survival Rate

The first two cases of Penicillium marneffei infection in humans were reported in 1959 and 1973. There had been no additional clinical reports of penicilliosis marneffei, until the five new cases of human infection described in this paper, the first from Thailand. The patients, three of whom died, came from various parts of the country. Their common clinical manifestations were fever and generalized lymphadenopathy, with multiple soft tissue, bone, joint and pulmonary involvement. Pericarditis with effusion was also seen. The diagnosis was established by isolating and identifying a dimorphic Penicillium species that produced a soluble red pigment in its mycelial form. The histopathologic features of the lymph nodes and bone marrow were similar to those of histoplasmosis capsulati. However, the yeast-like tissue form of P. marneffei divides by fission; that of Histoplasma capsulatum by budding. Treatment with amphotericin B was effective when this antifungal antibiotic was administered early in the course of the disease.

Topics: Adult; Amphotericin B; Child; Female; Humans; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Male; Middle Aged; Mycoses; Penicillium; Pregnancy; Pregnancy Complications, Infectious; Thailand; Tuberculosis