These results demonstrate that the BR combination is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas.

BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.

The present study indicates that reactive oxygen species induced by high glucose are involved in both death-receptor- and mitochondrion-dependent apoptosis in the heart in vivo. It also suggests that antioxidants may be a therapeutic option for preventing cardiovascular damage in diabetes mellitus in humans.

Bendamustine as a single agent is effective against aggressive lymphoma, even in cases of refractory disease. Further studies are warranted to determine the significance of bendamustine in the treatment of aggressive lymphomas.

Treatment of patients in remission of acute myelocytic leukemia using immunotherapy with interleukin 2 is a new approach to prolonging remission duration in this disease. As an important mechanism for the pathophysiology of eradication of residual myelocytic blast populations, activation of cytotoxic effector lymphocytes has frequently been discussed. However, the associated immunological research has been complicated to some extent, because in conventional chromium 51-release assays, blast cells frequently fail to incorporate sufficient amounts of 51Cr and/or spontaneously release high amounts of 51Cr. Recently, we established a culture system which promotes the outgrowth of cytotoxic T lymphocytes in bone marrow-derived mononuclear cells cultured in IL-2. To study cytotoxicity and the responsible mechanisms of the obtained T-cell lines and clones, we modified a previously described cytotoxicity assay, based on the release of lactate dehydrogenase (LDH-release assay) for use in cryopreserved blasts obtained from the bone marrow of patients with acute myelocytic leukemia. Using this assay, we were able to detect cytotoxicity of IL-2-activated peripheral blood lymphocytes from three healthy controls against a number of blast samples obtained from the bone marrow of patients with AML (up to more than 40% lysis at an effector target cell ratio of 20:1). However, a minority of AML blasts seem to be resistant to lysis by IL-2-activated lymphocytes. In bone marrow-derived T-cell lines from patients with AML we detected lytic activity against autologous blasts in three of seven cases tested by LDH release, ranging from 29 to 63% at an effector target ratio of 10:1. Additionally, T-cell clones with different phenotypes were established which were able to mediate cytotoxicity against autologous blast cells. Thus, cytotoxicity against freshly isolated blasts from patients with acute myelocytic leukemia can be analyzed reliably, reproducibly, and without the use of isotopes by the LDH-release assay.

Non-Hodgkin's lymphoma is an AIDS-defining disease. The impact of HAART on the epidemiology and prognosis is debated controversially. A retrospective analysis has been performed in order to determine the influence of HAART. We collected data of 214 cases of AIDS-related Lymphoma (ARL) treated at our centre from January 1984 until May 2003 and analysed them using the Kaplan-Meier-, log rank- and Cox proportional hazard-model. The incidence of ARL increased between 1991 and 1994 up to a peak of 14.83 per 1000 patient years. In the subsequent periods from 1995 onwards however, it decreased to 3.7 in 1000 patient years. The incidence of AIDS-related primary CNS lymphomas (PCNSL) took a comparable, yet more pronounced development. Using the univariate Kaplan-Meier analysis prolonged survival was significantly associated with the achievement of a complete remission as well as with a favourable virological response to HAART. No significant differences could be shown for the use of protease inhibitors as well as for virological response being achieved before the diagnosis of NHL. When using the Cox model, complete remission overrides viral response and thus remained the only independent prognostic factor. Classical prognostic factors (CD4 count, prior Kaposi Sarcoma, extranodal manifestation, staging and histological subtype of NHL) were no longer significant for HAART patients in the multivariate analysis. These results illustrate the requirement for new prospective studies in order to determine the best options and ideal timing of coadministering chemotherapy and the type of HAART. Furthermore this study demonstrates that HAART decreases the incidence of ARL, and that achievement of a complete remission in patients suffering from ARL is--according to the multivariate analysis--the single most important prognostically relevant factor with respect to the time of survival.

No abstract

Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and low-grade non-Hodgkin lymphomas (NHLs). Here, the clinical experience and side effects with FAMP are reported in 77 patients with pretreated CLL (59 B-CLL, 2 T-CLL) and low-grade NHLs (9 immunocytic lymphomas including 5 Waldenström's macroglobulinaemia, 2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients are evaluable for response. All except 8 patients were pretreated with one to four different regimens and had progressive disease. FAMP was administered at a dosage of 25 mg/m2 daily for 5 days as 30 minute infusion every fifth week. Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%) of evaluable patients with CLL, respectively. In 7/8 (1 x CR, 6 x PR) evaluable patients with immunocytic lymphoma and in 3/6 (3 x PR) patients with cc or cb-cc lymphoma remissions were obtained. The probability of progression-free survival was 66% and the event-free survival was 25% and 22% at 12 and 18 months. The median progression-free survival until relapse or death, however, was only 7 months (2-20+). Major toxic effects included infections in 22 patients (grade 3 and 4 WHO), granulocytopenia (mainly grade 3) and nausea in 8 patients (mainly grade 1). 19/22 patients were in PR at the time of occurrence of infectious complications. Meanwhile, 14 patients died due to septicaemia, pneumonia or other infections. Nine patients developed severe septicaemia, 4 patients had pneumocystis carinii or aspergillus pneumonias. The high infection rate may not only be due to hypogammaglobulinaemia and granulocytopenia induced by FAMP but also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4+ cells/microliters after 6 cycles of FAMP. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. It is concluded that FAMP is effective even in patients with advanced CLL and low-grade NHLs refractory to multiple chemotherapy regimens. However, FAMP has a marked suppressive effect on granulocytes and T-lymphocytes, predominantly CD4+ lymphocytes.