Antimycotic therapy with liposomal amphotericin-B for patients undergoing bone marrow or peripheral blood stem cell transplantation.

Suspected deep or systemic mycosis in patients undergoing high-dose therapy and autologous or allogeneic bone marrow transplantation (BMT) requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional amphotericin-B is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients often receive other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 74 BMT-patients treated with liposomal amphotericin-B for culture-documented aspergillosis (n = 5) or candidiasis (n = 6), or for serologically (n = 35) or clinically suspected mycosis or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.8 (0.64-5.09) mg/kg body-weight and continued for 13 (1-55) days. The drug was excellently tolerated and only in one was therapy stopped due to severe chills and fever. Severe organ impairment was not observed under therapy with liposomal amphotericin-B. Creatinine decreased in five patients after an increase under preceding therapy with the conventional formulation. Influence of liposomal amphotericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 10/11 culture-positive patients died from aspergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, and VOD. Liposomal amphotericin-B was effective in preventing relapse of systemic mycosis in 10/12 patients with a history of aspergillosis (n = 11) or candidiasis (n = 1). We conclude, that favourable toxicity of liposomal amphotericin-B should encourage dose escalation studies of liposomal amphotericin-B randomised against the conventional formulation and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional risk factors of the BMT-patients.

Fatal outcome of disseminated candidosis after allogeneic bone marrow transplantation under treatment with liposomal and conventional amphotericin-B. A report of 4 cases with determination of the Mic values.

Four patients undergoing allogeneic bone marrow transplantation were treated with liposomal (3 patients) and conventional (one patient) amphotericin-B for disseminated candidosis. Candida krusei was isolated from 3, and C. glabrata from 1 patient. The patients were treated with liposomal amphotericin-B in doses from 3 to 5 mg/kg. The fourth patient received conventional amphotericin-B in a reduced dose due to renal impairment. The patients died from multiorgan failure due to disseminated fungal infection. In 1 case, the switch to the conventional drug resulted in clearance before death. The 3 fungus isolates, together with the fourth strain obtained from patient no. 4 without any exposition to liposomal amphotericin-B were tested for their susceptibility to conventional, liposomal and discoidal amphotericin-B. All strains showed good sensitivity to the conventional and discoidal drug. The minimal inhibitory concentrations (MIC) of liposomal amphotericin-B were 1 to 3 titre steps higher indicating a reduced sensitivity of the tested strains to this preparation. We conclude that the use of liposomal amphotericin-B is recommended mainly on the base of the low incidence of side-effects. Intensive microbial resistance tests, pharmacokinetic investigations and randomized studies are necessary before the conventional drug is replaced as the gold standard for systemic antimycotic therapy.

[Primary pleural metastasis of osteosarcoma]. / Primäre pleurale Metastasierung eines Osteosarkoms.

We describe the case of a 18-year-old male patient presenting primary pleural metastasis with osteosarcoma at the proximal right tibia. Clinical signs, therapy and imaging methods are demonstrated. Differential diagnosis is described.

Early toxicity of intensified conditioning with etoposide combined with total body irradiation/cyclophosphamide or busulfan/cyclophosphamide in children undergoing autologous or allogeneic bone marrow transplantation.

In recent years, high dose chemotherapy followed by bone marrow rescue has been established as a common treatment of hematologic and solid tumor malignancies. Despite unequivocal success, relapse after transplant remains a serious problem, being the main cause of treatment failure. In an attempt to reduce relapse rates, we intensified the conditioning regimens consisting of busulfan/cyclophosphamide versus fractionated total body irradiation (f-TBI)/ cyclophosphamide by the addition of high dose etoposide. Toxicity profiles of 25 pediatric patients with hematologic malignancies undergoing intensified conditioning did not differ significantly between the two groups, except for a higher incidence of veno-occlusive disease in busulfan-treated patients (3 of 13 patients) compared with the TBI group (0 of 12 patients). We observed no transplant-related mortality in neither group. Regimen-associated morbidity was moderate and reversible in all cases. Five patients died in each treatment arm, due to relapse of the underlying disease. We conclude that both regimens are feasible in marrow transplantation of pediatric patients. Open randomized trials are needed to assess the efficacy of intensified conditioning in terms of disease-free survival.

Cyclophosphamide/antithymocyte globulin conditioning of patients with severe aplastic anemia for marrow transplantation from HLA-matched siblings: preliminary results.

Many approaches have been taken to reducing the rate of graft failure and the incidence of graft-versus-host disease (GVHD) in bone marrow transplantation (BMT) of patients with severe aplastic anemia (SAA). The combination of cyclophosphamide with irradiation has had unequivocal success in reconstituting a sustained engraftment, but this procedure has severe associated risks such as second malignancies. Recently, cyclophosphamide (CYC) plus antithymocyte globulin (ATG) has been shown to be an effective alternative to irradiation-based programs in retransplants. Based on these experiences, the current clinical trial was started to prepare patients suffering from SAA for marrow transplantation from HLA-identical siblings with ATG plus CYC. Nine patients have been enrolled into the study so far. They received a total dose of 200 mg/kg CYC and concomitantly 120 mg/kg or 90 mg/kg ATG, followed by cyclosporine plus methotrexate as post-transplantation GVHD prophylaxis. Eight of nine patients survived without any transplant-associated complications; i.e., they had a documented stable engraftment without rejection and without acute or chronic GVHD. One patient died due to an Aspergillus sepsis prior to a definite engraftment. Although our data are preliminary because of the small number of patients enrolled and a follow-up of only 30 months, CYC plus ATG appears to be an effective preparative regimen for BMT in patients with SAA, resulting in a favorable outcome.