Background. Cyclophosphamide-induced urothelium cancer of the bladder is a well-known entity, The risk for inducing such cancer grows with duration and dosage of cyclophosphamide therapy. The lag time between termination of treatment and development of urothelial cancer has been observed to be between 9 months and 11 years. Single cases have been reported 14, 16, 17, and 21 years after cyclophosphamide treatment.Case. We report a case of a bladder cancer occurring after a lag time of 20 years after oral therapy with cyclophosphamide for ovarian cancer. The bladder cancer was detected due to gross hematuria.Conclusion. It is of great importance for gynecologists to continue to care for patients who have received long-term cyclophosphamide treatment, even if the treatment was completed decades ago. One possible early symptom of cyclophosphamide-induced bladder cancer is painless hematuria. This can easily be used to detect bladder cancer in women at risk, even after a very long latency period, (C) 2001 Academic Press.

Chemotherapy-induced febrile neutropenia makes the immuncompromized cancer patient even more susceptible to severe infections. The risk of infections correlates with grade and duration of febrile neutropenia. Empiric antibiotic treatment can diminish the high infection-associated mortality. There are guidelines for antimicrobial treatment and modifications of therapy. To individualize therapy decisions, it is helpful to characterize high- and low-risk patients. Antibiotic prophylaxis in afebrile neutropenic patients is only indicated in special cases. Use of G-CSF for prophylaxis of neutropenia can be recommended for high-risk patients, but it should not be used for the treatment of infection.

The bcl‐2 gene is an important antagonist of apoptosis, the programmed cell death. Bcl‐2 is highly expressed in a variety of lymphomas. Lymphocytes of patients with chronic lymphocytic leukemia (CLL) express high amounts of bcl‐2 even in the absence of the t(14;18) translocation, resulting in a strong resistance towards corticosteroid induced apoptosis. Within the 5′‐untranslated region of the bcl‐2 gene a p53 dependent negative response element has been described. Genetic alterations within this element could lead to uncontrolled overexpression of bcl‐2 and subsequent resistance towards apoptosis. We therefore analyzed the mRNA from the 5′‐untranslated region −279 to −85 bp of the bcl‐2 gene by direct PCR sequencing from peripheral blood derived lymphocytes from patients with CLL and normal healthy donors. Compared to published sequences (Tsujimoto and Croce (1986) Proc. Natl. Acad. Sci. USA 83, 5214), we consistently found an exchange at position 1271 from A to G and at position 1284 from G to A in all CLL as well as normal donor derived samples analyzed. Thus, CLL specific alterations compared to normal cells could not be found and deregulated expression of bcl‐2 in CLL cells does not appear to be due to alterations in the p53 dependent negative response element of the bcl‐2 gene. However, our data add information to published sequence data of this region. © 1997 Federation of European Biochemical Societies.

Burkitt's lymphoma (BL) cell lines are heterogenous with regard to phenotype, growth characteristics, Epstein-Barr virus (EBV) latent gene and BCL-2 expression. Previously we have demonstrated that transfection with the EBV genes LMP or EBNA-2 upregulates BCL-2 in B-cell lines. In order to test the functional relevance of these findings, cell lines were examined with regard to their sensitivity towards different apoptosis-inducing agents. BL cell lines transfected with LMP expressed high levels of BCL-2, and were compared with the parental cell line expressing little or no BCL-2. We also studied EBV immortalized lymphoblastoid cell lines (LCL) with high BCL-2 expression and strong resistance towards low serum concentrations. Hydrocortisone (HC) and 2-chlorodeoxyadenosine (2-CDA) were used alone or in different combinations. Cell growth and apoptosis were studied morphologically and by determination of viability and DNA fragmentation. BL cell lines showed different sensitivity towards HC-induced apoptosis, and sensitive cell lines became more resistant towards HC after infection with EBV or transfection with LMP and subsequent upregulation of BCL-2 expression. BL cell lines and LCL were relatively insensitive towards 2-CDA-induced apoptosis, and high concentrations of 2-CDA were necessary, independently of the levels of BCL-2 expression. In contrast to low-grade non-Hodgkin's lymphomas, 2-CDA does not appear to be a valuable drug for the treatment of Burkitt's lymphoma. LMP expression provides resistance towards hydrocortisone-induced apoptosis in vitro, possible through upregulation of BCL-2.