amphotericin-b and Leukemia-Lymphoma--Adult-T-Cell

Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB-PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Daunorubicin; Dimyristoylphosphatidylcholine; Drug Carriers; Female; Follow-Up Studies; Fusarium; Granuloma; Hepatitis; Humans; Immunocompromised Host; Kidney Diseases; Leukemia-Lymphoma, Adult T-Cell; Mycoses; Neutropenia; Phosphatidylglycerols; Prednisone; Recurrence; Splenic Diseases; Vincristine

A rare case of 70-year-old woman with adult T-cell leukemia/lymphoma who developed multifocal choroiditis from a dissemination of Cryptococcus neoformans is reported. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. Sequential optical coherence tomographic images disclosed the involvement of the choroid and the consecutive changes in its architecture during the course of treatment. The recognition of these ocular manifestations may be important for the rapid diagnosis of C. nerformans-disseminated diseases. Rapid diagnosis and prompt therapy with intravitreal injection as well as systemic fosfluconazole and liposomal amphotericin B led to clinical improvement of intraocular cryptococcosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Cryptococcus neoformans; Eye; Eye Infections, Fungal; Fatal Outcome; Female; Fluconazole; Humans; Intravitreal Injections; Leukemia-Lymphoma, Adult T-Cell; Multifocal Choroiditis; Organophosphates; Tomography, Optical Coherence

Systemic candidiasis is a rare but life threatening complication in immunosuppressed patients undergoing allogeneic SCT. Combination of new antifungal agents may improve outcome in this patient population. Here, triple anti-mycotic therapy is described in an relapsed ALL patient in urgent need of allogeneic bone marrow transplantation. The patient with T-cell acute lymphoblastic leukemia of thymic differentiation achieved remission after treatment according to the German ALL protocol 07/03. Two months after the consolidation therapy relapse occurred requiring high dose chemotherapy with allogeneic stem cell transplantation. One day after start of the conditioning regimen the patient showed skin manifestations typical for septic mycosis and blood cultures became positive for Candida krusei while on fluconazole prophylaxis. Because of the limited sensibility of fluconazole resistant candida species to liposomal amphotericin B and the high mortality rate in patients with systemic candidiasis, voriconazole was added immediately to liposomal amphotericin B. Since fever did not resolve and the conditioning therapy for allogeneic transplantation was not yet completed caspofungin was added. Skin manifestation responded to this triple anti-mycotic combination and peripheral blood stem cells from an unrelated donor were transplanted. With the triple antifungal therapy the patient finally became afebrile, skin manifestations showed complete resolution and blood cultures became negative. Three months after the onset of systemic candidiasis the patient was fully active with no signs of fungal infection and in haematological and molecular remission. Mycotic sepsis at the start of myeloablative conditioning therapy in heavily pretreated acute leukemia patients is usually considered as not allowing successful allogeneic transplantation. Thus this case demonstrates, that allogeneic stem cell transplantation is feasible in patients presenting with systemic candidiasis if combined antifungal therapy with liposomal amphotericin B, caspofungin and voriconazole is given.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia-Lymphoma, Adult T-Cell; Lipopeptides; Liposomes; Male; Peptides, Cyclic; Pyrimidines; Transplantation Conditioning; Transplantation, Homologous; Triazoles; Voriconazole

Pulmonary mucormycosis is a usually fatal opportunistic infection in immunocompromised patients. We describe the first case of an adult patient with hematological malignancy and profound neutropenia to survive a disseminated pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined with high doses of liposomal amphotericin B and surgical resection may have contributed to the successful outcome.

Topics: Amphotericin B; Antifungal Agents; Combined Modality Therapy; Humans; Leukemia-Lymphoma, Adult T-Cell; Liposomes; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Neutropenia; Pneumonectomy; Radiography; Rhizomucor; Treatment Outcome

Hepatosplenic candidiasis following granulocytopenic periods is a relatively recently recognised problem in immunocompromised patients, particularly in those with acute leukaemia. We present three patients in whom diagnosis of hepatosplenic candidiasis was suspected on the basis of ultrasonographic (US), computed tomographic (CT) findings and confirmed by laparoscopy and biopsy of liver lesions. All three patients were successfully treated briefly with amphotericin B, followed by a longer period of fluconazole. In one patient laparotomy and surgical evacuation of abscesses was performed. This condition could be more often recognised by careful follow-up of liver function test, C-reactive protein level, ultrasonography, CT and MRI after recovery from chemotherapy-induced neutropenia.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Female; Fluconazole; Humans; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Neutropenia; Opportunistic Infections; Splenic Diseases

The case of a female patient with acute lymphoblastic leukaemia and chronic disseminated candidiasis, who was refractory to 1.8 g conventional amphotericin B therapy, is reported. She experienced severe amphotericin-B-related side-effects in spite of pretreatment, but was subsequently successfully treated with 3 g of a small unilamellar liposome formulation of amphotericin B prepared from soya phosphatidylcholine and cholesterol in a 7:3 molar ratio at our institute. The patient experienced minimal side-effects with this preparation, although no pretreatment was given. Liposomal amphotericin B prepared in our institute appears to be a safe and effective therapy for systemic fungal infections. However, large controlled studies are required to determine more precisely the potential of liposomal amphotericin B in the treatment of severe systemic fungal infection.

Topics: Adult; Amphotericin B; Candidiasis; Drug Carriers; Drug Resistance, Microbial; Female; Humans; Immunocompromised Host; Leukemia-Lymphoma, Adult T-Cell; Liposomes

Fungal infections are increasingly being reported in patients with acute leukaemia on intensive induction chemotherapy protocols. The common fungi seen are candida, aspergillus and mucormycosis. We have seen 3 cases of mucormycosis over the last 4 years. All 3 patients had acute leukaemia-two had acute lymphoblastic and one acute myeloid leukaemia. All patients were in neutropenic phase after induction chemotherapy. Features suggestive of fungal infection were fever and development or progression of pulmonary infiltrates despite antibiotic therapy. Repeated body fluid cultures were negative in two patients. In the first patient, the diagnosis was confirmed after biopsy of a palatal mass; he was treated successfully with amphotericin-B. In two patients the diagnosis was confirmed at autopsy. A high degree of suspicion in febrile, neutropenic cancer patients on chemotherapy and early administration of amphotericin-B may improve the outcome. With dissemination, the prognosis is poor.

Topics: Adolescent; Adult; Amphotericin B; Female; Humans; Infusions, Intravenous; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucormycosis; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography