Summary:Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and subsequent autologous or allogeneic haemopoietic stem cell transplantation, despite the change from topical to systemic anti-infection prophylaxis and the introduction of growth factors and new antimicrobial drugs. We report our single centre experience with data from 409 patients treated at our unit from its opening in 1990 until May 1997. Three hundred and seventy-eight patients were transplanted for the first time, 12 patients were retransplanted or boosted and 19 patients were readmitted for miscellaneous reasons. 245 patients were allografted and 157 autografted. Antimicrobial prophylaxis was mainly quinolones, fluconazole plus amphotericin-B orally, aciclovir, and TMP/SMX or pentamidine. Three hundred and nineteen (78%) developed fever of significantly longer duration in the allogeneic setting with anti-CMV seropositivity. The most frequent infection was fever of unknown origin (50.6%), followed by septicaemia (12.5%) and pneumonia (11.0%). Pathogens isolated in 24.6% of the infections were mostly grampositive bacteria (57.9%), followed by non-fermenting rods (11.2%), Aspergillus spp. and Candida spp. Systemic infection with these pathogens is associated with a poor prognosis. Antimycotic prophylaxis and the therapy must be improved.

Summary:A five-agent GVHD prophylaxis programme consisting of cyclosporin A, methotrexate, anti-thymocyte-globulin, pentaglobin and metronidazol was given to 48 recipients of unrelated donor marrow with chronic myelogenous leukemia, acute leukemia, myelodysplastic syndromes, and familiar lymphocytic hemophagocytosis of an average age of 33.5 (0.6-56) years. GVHD grades II-IV occurred in 18 patients (39%) and grades III-IV in five patients (11%). Chronic GVHD developed in nine patients (23%), three limited and six extensive. Fifteen patients died. Clinical relapse was detected in eight patients. Four patients died as a consequence of the underlying disease and subsequent treatment, 11 patients died of transplant-related causes. After a median follow-up of 19 months, the overall and diseasefree survival are 67% and 62%, respectively. Survival by age is as follows: 0-19 years: 12/13 patients; 20-39 years: 14/25 patients; 40-59 years: 7/10 patients. The five-agent GVHD prophylaxis regimen is effective. Matched-unrelated donor transplants can be carried out safely in patients younger than 50 years of age. The results in patients younger than 20 years of age should encourage matched-unrelated donor transplants at earlier stages of the disease.

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the ‘proven’ group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients.

Summary:We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30-45 mg/kg) and cyclophosphamide (120 mg/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan (16 mg/kg) instead of TBI. Nineteen patients were transplanted in 1CR, two in 2CR, one in 1PR and two in relapse. Major toxicity was mucositis grade II according to the Bearman scale in all patients. The treatmentrelated mortality was 25%, mainly due to infection or GVHD after allogeneic transplantation. After a median follow-up of 45 months (range 2-93), nine patients (37.5%) remain alive in CR. Nine patients (37.5%) relapsed and eight (33.3%) of these subsequently died. After autologous transplantation, four of five patients (80%) relapsed and died. Late relapse was seen after allogeneic, as well as autologous transplantation, at 33 and 59 months, respectively. The Kaplan-Meier estimate of leukemia-free survival for all patients is 38% at 3 years (95% CI: 18-58%) and 35% at 5 years (95% CI: 15-55%). For allogeneic transplants in first CR (n = 15) the estimate of disease-free survival was 46% at 3 years (95% CI: 19-73%) and 34% at 5 years (95% CI: 17-51%). Patients aged below 30 years had a better estimated overall survival at 3 years (61% vs 11%, P Ͻ 0.001). The bcr-abl fusion transcript (p210 vs p190 vs p210/190) did not affect disease-free or overall survival. In our experience, an intensified conditioning regimen seems to improve the results of bone marrow transplantation in patients with Ph؉ acute lymphoblastic leukemia. However, the high relapse rate warrants novel approaches to enhance anti-leukemic efficacy.

60 patients undergoing bone marrow or stem cell transplantation were treated with liposomal Amphotericin-B for documented or suspected mycosis. 34 patients had a prior course of conventional Amphotericin-B with the following adverse effects: increasing creatinine above 1.4 mg/dl (n = 17), increasing creatinine below 1.5 mg/dl (n = 9), no response (n = 6), and clinical side-effects (n = 4). Liposomal Amphotericin-B failed in 6/7 patients with culture-proven mycosis who died from infection with Aspergillus (n = 2) and Candida (n = 4), respectively. One patient with Candida lambica sepsis was cured. No patient with clinically or serologically suspected or diagnosed infection died from mycosis. Liposomal Amphotericin-B was well tolerated in 57 patients, even after side-effects of the conventional formulation. Adverse effects occurred in three cases, requiring the withdrawal of the drug in one patient. Due to toxic side-effects of the high-dose therapy and transplant-related complications, it was difficult to evaluate the influence of liposomal Amphotericin-B on laboratory parameters. Eight patients showed a decrease of creatinine levels, which had increased above normal values under preceding therapy with conventional Amphotericin-B. Liposomal Amphotericin-B is well tolerated in patients undergoing high-dose therapy and bone marrow transplantation. The efficacy of liposomal Amphotericin-B needs to be investigated in randomized studies in comparison with conventional Amphotericin-B.