Ten patients with B-chronic lymphocytic leukemia (B-CLL) (Six Stage A and four Stage B), who had not received therapy previously, were treated with recombinant alfa-2b-interferon (Schering Corporation, Kenilworth, NJ). The low dose of 1.5 MU was administered by intramuscular (IM) injection three times a week for the first week. The dose was increased to 3.0 MU thereafter until 3 months of therapy were completed. In the responding patients, treatment was continued in the same dose and schedule for 3 additional months. Interferon was tolerated without major toxicity by most patients. Objective tumor response (one complete response and four partial hematologic responses [PHR]) was observed in five of ten patients (50%). Severe autoimmune hemolytic anemia developed in one of the nonresponders at 8 weeks. Therefore, treatment had to be discontinued. Our study demonstrated single alfa-2b-interferon antitumor activity in untreated B-CLL patients with stable disease, and indicated that further trials of alfa-2b-interferon, possibly combined with chemotherapy, may be justified.
degradation. In addition, we provide for the first time experimental evidence that the acid secreted upon metabolic activation is not only a product of anaerobe (lactate, acetate) or aerobe (carbonate) glycolysis, but may be associated with a specific V-ATPase located in vacuolar membranes in the cytoplasm or on the surface of the cells. Preliminary data corroborate this conclusion, since a V-ATPase was located on the cell surface by immunohistochemistry and a V-ATPase encoding mRNA was detected by RT/PCR in the respective cells. REFERENCES 1 Parak, et al. Metabolic activation stimulates acid production in synovial fibroblasts. J Rheumatol. 2000;27:2312 2 Sainsbury, et al. Cathepsin K expression by activated fibroblasts at the bone interface of the pseudosynovium in aseptic prosthesis loosening. Proc. ORS Conv. Anaheim # 27, 1999 3 Mast A. Charakterisierung von Knochenzellen mit biophysikalischen Methoden auf zellulärem Niveau, Master Thesis,
The value and exact type of intensive chemotherapy of unselected elderly AML patients in terms of overall survival (OS) and quality of life remains controversial. Despite recent improvements in supportive measures during cytotoxic therapy, elderly AML patients continue to exhibit lower remission rates, higher toxicity, more relapses and eventually a worse survival. The present analysis evaluates in a retrospective manner the outcome of 57 homogeneously treated AML patients >60yrs during a period of 70 months (Nov 2001 to Aug 2007). The protocol schedule included an initial course of mitoxantrone+ cytarabine 3+5 (12mg/m2/d and 100mg/m2 q12h respectively) followed by a second abbreviated course of mitoxantrone+ cytarabine 2+5, followed by a final course of idarubicin+cytarabine+ thioguanine 2+7+7 (10mg/m2/d, 100mg/m2 q12h and 100mg/m2/d respectively). G-CSF at 5μg/Kg was added to all courses to accelerate hematopoietic recovery. Our patient population consisted of 30 cases of de novo AML and 27 cases of secondary AML (MDS 26, NHL 1) classified according to FAB as follows: M0 (6), M1 (7), M2 (25), M4 (7), M5 (4), M6 (6), hybrid-leukemia (2). Their median age was 70 yrs (range 63–80, mean 70,3 yrs) and M/F ratio was 35/22. Cytogenetic analysis was performed in 52/57 cases: 6/57 cases failed to produce metaphases, 32 cases revealed standard risk abnormalities (twenty six normal karyotype, six trisomy 8) and 7/52 cases had poor risk abnormalities. Leukocytosis >50X109/L was noted in 12/57 and leukopenia<5X109/L was noted in 22/57 patients. After a median observation period of 9 months (range 1–70) the following results are available: 26/57(45,6%) patients entered CR (15 de novo, 11 secondary) post-course 2 and their median OS is 15 months (range 2–63). An additional 6/57(10,5%) cases returned to a myelodysplastic phase without excess of blasts achieving thus partial hematological remission. The remaining 25/57(43,8%) patients proved primary resistant and deceased after a median of 3 months (range 1–22). One resistant case survive in remission attained off protocol. Within the group of remitters 3/26 deceaced from complications (MI, fungal infection, sepsis) before the next chemotherapy course. The remaining 16/26 remitters relapsed after a median of 8 months (range 1–12,5); fourteen of them deceaced and two are alive for 63 and 16 months respectively (one as a result of salvage treatment and the other with on going disease). Finally 7/26 cases remain alive and disease-free. Due to the short follow up, median OS for the whole cohort was estimated to date at 7,5 months. Conclusion: Combination chemotherapy with mitoxantrone and cytarabine is well-tolerated and reasonably effective in elderly AML patients. With a total response rate of 56,1% (CR+PR) and an induction death rate of 3,4%(2/57), the current schedule deserves further evaluation in a larger AML population. Furthermore, our data validate the improvement in survival of those patients achieving CR as suggested by other studies.
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