Efficacy and safety of imatinib mesylate (Glivec) in combination with interferon-alpha (IFN-alpha) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Imatinib has marked antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), but secondary resistance develops rapidly, reflecting the limitations of single-agent therapy. Experimental data suggest that interferon-alpha (IFN-alpha) enhances the antileukemic activity of imatinib. We therefore examined combined imatinib and low-dose IFN-alpha in six patients with Ph+ALL who were ineligible for stem cell transplantation. All patients had received imatinib for 0.5-4.8 months prior to IFN-alpha, for relapsed (n=3) or refractory (n=1) Ph+ALL or as an alternative to chemotherapy following severe treatment-related toxicity (n=2). Five patients were in hematologic remission (CR) with minimal residual disease (MRD+), one patient was refractory to imatinib. Four of the five MRD+ patients are alive in CR after a median treatment duration of 20 (11-21) months. Two of these patients are in continuous CR 21 months after imatinib was initiated, while the other two patients experienced an isolated meningeal relapse that was successfully treated with additional intrathecal chemotherapy. Sustained molecular remissions were achieved in three patients and are ongoing 13 and 10.5 months after central nervous system (CNS) relapse and 6 months after starting concurrent IFN-alpha and imatinib, respectively. Marrow relapse occurred in one of the five MRD+ patients. Combination treatment was associated with a complete marrow response of 5 months duration in the imatinib-refractory patient. Imatinib combined with low-dose IFN-alpha may achieve prolonged hematologic and molecular remissions in a subset of patients with advanced Ph+ALL, who are not candidates for allogeneic SCT. CNS prophylaxis is necessary and may enhance the antileukemic activity of imatinib and IFN-alpha.

Intermittent 2-hour-infusion of cladribine as first-line therapy or in first relapse of progressive advanced low-grade and mantle cell lymphomas.

Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m2 cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 6-45+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate of 43% (95% CI: 29%-58%). Response rate for the group of 23 previously untreated patients with follicle center lymphomas was high with 96% overall response (95% CI: 78%-100%) and 57% CR rate (95% CI: 34%-77%). Cladribine also showed activity in patients with mantle cell lymphomas achieving a response rate of 58% (95% CI: 28%-85%). Myelosuppression was the major toxicity with 17% neutropenia grade 3 and 4. Thrombocytopenia was rare with only 2% grade 3 and 4. A prolonged CD4-lymphocytopenia was observed in all patients. Life threatening complications were not observed. These results confirm the major single-agent activity of cladribine in a large cohort of patients with untreated low-grade lymphomas using the intermittent 2-hour-infusion dosage-regimen. To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas.

[Clinical experience with bacterial contamination of Port-A-Cath systems in tumor patients]. / Klinische Erfahrungen mit bakteriell kontaminierten Port-A-Cath-Systemen bei Tumorpatienten.

In 33 cancer patients with subcutaneously implanted Port-A-Cath systems (Pharmacia) who developed bacteremia with rigor and high fever, aerobic and anaerobic cultures were prepared from aspirated chamber blood. Organisms were isolated from 19 patients of whom 10 had fever, but none life-threatening. In seven patients the fever was caused by infected chamber blood, while in three it was impossible to prove whether it was due to chamber contamination or the underlying disease. Almost all of the causative organisms were skin saprophytes, most frequently Staph. epidermidis, Acinetobacter Iwoffi and apathogenic Corynebacteria. The pathway of infection was probably exogenous (iatrogenic) inoculation. Removal of the catheter system was not necessary. Since strict hygienic measures were instituted when using the system no further chamber contamination has occurred.