Early Austrian multicenter experience with palonosetron as antiemetic treatment for patients undergoing highly or moderately emetogenic chemotherapy.

BACKGROUND: Palonosetron is a new generation 5-HT3-receptor antagonist with a significantly prolonged half-life and a once-a-day administration compared to the conventional setrons. To evaluate the antiemetic efficacy of palonosetron in the daily hospital practice setting, a postmarketing study was carried out in Austria. METHODS: Palonosetron was administered at 0.25 mg on day 1 of each cycle to 135 cancer patients who received moderately or highly emetogenic chemotherapy either as an IV bolus or as a short-term infusion. Two thirds of these patients were females (n = 90), the majority had breast cancer (n = 38) and the majority received cisplatin, carboplatin, anthracyclines, 5-fluorouracil or cyclophosphamide. RESULTS: The complete antiemetic response rate was 68 % overall with 87 % efficacy on day 1 and 72 % efficacy on days 2 to 5. Higher antiemetic response was achieved in male patients, in patients being aged > or = 50 years, and in chemonaive patients. Twenty-four percent of patients needed rescue medication. Only 1.5 % of patients reported mild adverse events. CONCLUSIONS: Palonosetron resulted in high antiemetic efficacy in this study. Female gender and age < or = 50 years should be particularly considered when the antiemetic regimen is selected.

Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma.

Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large-cell lymphoma (ALCL). We evaluated the presence, extent, and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK-positive ALCL at diagnosis using qualitative and quantitative polymerase chain reaction (PCR) for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 10(4) copies ABL (NCNs). BM was analyzed from 80 patients and PB from 52. BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histologic subtype. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-Rs): CI-R was 50% +/- 10% for 38 PCR-positive and 15% +/- 7% for 42 PCR-negative patients (P < .001). Sixteen patients with more than 10 NCNs NPM-ALK in BM had a CI-R of 71% +/- 14% compared with a CI-R of 18% +/- 6% for 59 patients with 10 or fewer NCNs (P < .001). PB PCR results led to a similar grouping. Thus, quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%.

Level of MYC overexpression in pediatric Burkitt's lymphoma is strongly dependent on genomic breakpoint location within the MYC locus.

Increased transcriptional activity of the MYC gene is a characteristic feature of Burkitt's lymphoma. Aberrant MYC expression is caused by (1) chromosomal translocation to one of the loci carrying an immunoglobulin gene, (2) mutation within the translocated allele, (3) loss of the block to transcription elongation, or (4) promoter shift. To investigate the influence of breakpoint locations within the MYC gene on MYC transcript levels, we determined both the precise genomic MYC/IGH breakpoints and the amount of MYC mRNA in 25 samples of pediatric Burkitt's lymphoma with translocation t(8;14)(q24;q32). Patients with breakpoints that were 5' from MYC exon 1 had significantly lower expression of MYC than did patients who had a breakpoint within exon 1 or intron 1 (P < 0.05 and 0.005, respectively). The highest mRNA level of MYC (1,006 copies per 100 copies ABL1) was detected in patients with loss of the first exon and transcription initiation from a cryptic P3 promoter within the first intron of the MYC gene. In contrast, there was no obvious correlation between breakpoint locations within the IgH locus and the amount of MYC mRNA.

Combined polymerase chain reaction methods to detect c-myc/IgH rearrangement in childhood Burkitt's lymphoma for minimal residual disease analysis.

BACKGROUND AND OBJECTIVES: The translocation t(8;14)(q24;q32), involving the c-myc gene (8q24) and the immunoglobulin heavy chain (IgH) locus (14q32), represents about 75% of all chromosomal translocations in Burkitt's lymphoma (BL). Due to the large variability of the breakpoint region, only the recently improved long-distance LD-polymerase chain reaction (PCR) allows the specific c-myc/IgH fusion to be identified at the genomic level. The sensitivity of the LD-PCR is only 10(-2) to 10(-3) due to the relatively large size of the amplification products (1 to 10 kbp). We, therefore, established a more sensitive nested PCR with a specific primer combination for each patient based on sequence analysis of the variant breakpoint regions. DESIGN AND METHODS: Using the combined PCR methods, we analyzed bone marrow and peripheral blood without visible blasts at diagnosis from 18 patients with t(8;14)-positive BL. RESULTS: In tests employing dilutions of genomic DNA from the BL cell line CA-46 in the T-cell lymphoma cell line KARPAS-299, which lacks the t(8;14), the sensitivity increased 100-fold, to 10(-5). However, the investigation of 18 c-myc/IgH-positive BL patients with each breakpoint-specific nested PCR showed an inter-patient variability of sensitivity between 10(-3) and 10(-5). Using this assay, the rearrangement was detected in 4/16 bone marrow samples and in 6/15 peripheral blood samples without visible blasts at diagnosis. INTERPRETATION AND CONCLUSIONS: Using the combined PCR methods the detection of c-myc/IgH reaches a level of sensitivity required for the evaluation of minimal residual disease (MRD) in BL patients. Furthermore, the results highlight the importance of verifying the patient-specific sensitivity level for individual MRD monitoring.