melphalan and Aspergillosis

The risk of invasive aspergillosis (IA) is considered to be low among autologous HSCT recipients, but an increase in the incidence has been observed recently in this setting. The aim of the study was to assess the influence of immunosuppressive drugs (steroids, rituximab, fludarabine, thalidomide), used in treatment of lymphoid malignancies during 6 months of pretransplant period, on IA incidence after autologous HSCT. A total of 109 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and multiple myeloma (MM), conditioned with carmustine, etoposide, cytarabine, melphalan or melphalan and transplanted with PBSC, were analyzed prospectively. Patients were monitored with twice-weekly galactomannan test. High-resolution computed tomograhy of the chest and bronchoscopy were performed in case of positive galactomanan test, persistent fever or pulmonary infiltrates. Documented IA was diagnosed in nine (8%) patients (three proven, six probable). The incidence of IA was comparable in NHL, HD and MM patients and not influenced by age, advanced disease or conditioning regimen. Factors significant for development of documented IA by univariate analysis were treatment with fludarabine (P=0.008) or rituximab (P=0.039). The only factor predicting documented IA by multivariate analysis was treatment with fludarabine (P=0.008). Patients treated with fludarabine or rituximab in pretransplant period are at risk of IA and require close monitoring and/or anti-mould prophylaxis.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Carmustine; Cyclophosphamide; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Lymphoproliferative Disorders; Male; Melphalan; Middle Aged; Neutropenia; Prospective Studies; Risk Factors; Rituximab; Vidarabine; Young Adult

The treatment of disseminated aspergillus infections in neutropenic patients remains a major challenge in spite of several new antifungal drugs. We report the case of a patient with multiple myeloma in prolonged neutropenia after primary failure of an autologous stem cell graft who developed invasive aspergillosis despite voriconazole monotherapy. He responded to a combination of voriconazole and caspofungin, supported by granulocyte transfusions and surgery. A subsequent allogeneic peripheral blood stem cell transplantation did not lead to recurring aspergillus infection. The patient is well and free of clinical disease with respect to the fungal infection and myeloma more than 18 months after the allogeneic transplantation.

Topics: Antifungal Agents; Aspergillosis; Caspofungin; Drug Therapy, Combination; Echinocandins; Granulocytes; Humans; Leukocyte Transfusion; Lipopeptides; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Myeloma; Necrosis; Peptides, Cyclic; Pyrimidines; Radiography; Stem Cell Transplantation; Transplantation, Autologous; Transplantation, Homologous; Triazoles; Voriconazole

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Melphalan; Neoplasm Recurrence, Local; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisone; Procarbazine; Salvage Therapy; Skin; Transplantation, Homologous; Vinblastine; Vincristine

A 59-year-old man with a 4-year history of light chain myeloma relapsing after two preceding autografts and salvage therapy with thalidomide underwent a peripheral blood stem cell (PBSC) transplant from his HLA-identical sister after conditioning with 100 mg/m2 melphalan. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine. Despite pulmonary infiltrates and sinusitis at the time of the allograft, it was decided to proceed with the transplant because the myeloma was refractory and rapidly progressive. Sputum cultures obtained 2 days before the allograft grew Aspergillus fumigatus 2 days post transplant. A fumigatus grew repeatedly on specimens obtained post transplant. Prompt hematologic recovery was seen with full donor-type chimerism. The fungal infection subsided gradually on a combination of amphotericin B lipid complex and itraconazole. A second aliquot of donor PBSC was infused electively on day +42 to induce graft-versus-myeloma. Complete remission of the myeloma was achieved by 75 days post transplant. No acute GVHD was seen. No chronic GVHD was seen at 16 weeks when he received the third PBSC infusion. He is currently alive and well in remission 9 months post transplant. This case demonstrates the safety and potential usefulness of allogeneic PBSC transplantation with reduced-intensity conditioning in patients with markedly compromised performance status.

Topics: Antineoplastic Agents, Alkylating; Aspergillosis; Graft vs Tumor Effect; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Transplantation, Homologous