Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia.

We treated 153 patients with de novo acute myeloid leukemia (AML) with two induction courses of conventional-dose cytosine arabinoside (ara-C) and idarubicin (AIDA) followed by either a third course of AIDA, high-dose ara-C or bone-marrow transplantation. The complete remission (CR) rate for all patients was 63.4%, with a higher CR rate for patients with a normal (versus unfavorable) karyotype (73.2% vs 52.5%; P=0.038). The probability of overall survival (OS) was 30.7% after 5 years (26.3% after 7 years). Improved OS at 5 years could be observed for patients up to 50 years old versus patients older than 50 years of age (37.6% vs 19.9%; P=0.001) and patients with a normal (versus unfavorable) karyotype (42.9% vs 14.1%; P=0.0016). Disease-free survival (DFS) after 5 years was 33.2% for all 97 CR patients and was significantly better for patients with a normal (versus unfavorable) karyotype (44.3% vs 12.3%; P= 0.003). Multivariate analysis revealed that the age for OS (P < 0.02) and the karyotype for both OS (P<0.03) and DFS (P< 0.05) were independent prognostic factors. In conclusion, AIDA is an effective and well-tolerated induction regimen (even in elderly patients) with a 5-year survival of more than 30% when combined with ara-C-containing postremission therapy. The karyotype is the most powerful prognostic factor for predicting the outcome of patients treated with this protocol.

Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity.

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.

Antigenic phenotyping of lymphoid cells and B cell gene rearrangement in type B gastritis and in gastritis not associated with Helicobacter pylori colonization.

Marginal-zone B cells of the mucosa-associated lymphoid tissue (MALT) are the normal counterpart of the neoplastic cells in MALT lymphoma. In both cases these lymphocytes express surface immunoglobulins, but are negative when stained for B cell associated antigens like CD10 and CD23. Furthermore, the B cell gene rearrangement has been found in Helicobacter pylori associated chronic gastritis and in extranodal type of marginal-zone lymphoma. The aim of this study was to quantify the number of IgM-, CD10-, and CD23-positive lymphocytes in patients with type B gastritis and to compare the results with the antigen profile of mononuclear cells in patients with gastritis not associated with H. pylori. Additionally, the immunoglobulin heavy-chain (IgH) gene rearrangement in H. pylori positive and H. pylori negative gastritis was studied. From 23 patients with a positive urease test and/or histologically proven H. pylori infection and chronic gastritis and from 22 patients with H. pylori negative chronic gastritis mucosa biopsy specimens were taken. Single-cell suspensions were obtained following enzymatic digestion. For immunocytochemistry, an alkaline phosphatase-antialkaline phosphatase method was applied. IgH gene rearrangement in formalin-fixed, paraffin-embedded specimens was determined by polymerase chain reaction in 11 patients with chronic gastritis. An increase in mu-positive plasma cells and B lymphocytes was detected in patients with H. pylori positive gastritis as compared with patients with H. pylori negative gastritis (10.0 vs. 3.9%, p < 0.001, and 4.3 vs. 1.6%, p < 0.01, respectively). In both groups, the proportion of CD10- and CD23-positive lymphocytes was <1%. IgH gene rearrangement was not restricted to type B gastritis; single bands were also present in 3 of 7 patients with H. pylori negative chronic gastritis. Our finding of IgH gene rearrangement in some of the patients with H. pylori negative chronic gastritis indicates that additional factors may be critical for these genotypical changes and for the pathogenesis of gastric MALT lymphoma.