[Minimal residual disease analysis in acute lymphoblastic leukemia of childhood within the framework of COALL Study: results of an induction therapy without asparaginase]. / Minimal Residual Disease Untersuchungen bei der akuten lymphatischen Leukämie im Kindesalter im Rahmen der COALL-Studie: Ergebnisse einer Induktionstherapie ohne Asparaginase.

UNLABELLED: The detection of minimal residual disease (MRD) is a major prognostic factor for treatment in acute lymphoblastic leukemia (ALL) of childhood. Several groups showed the predictive value of MRD after 5 weeks of chemotherapy (at the end of induction therapy). Patients with more than 1 leukemic cells in 100 cells (> or = 10(-2)) at this time-point have a significantly higher relapse rate. The MRD measurement has been shown to be an independent prognostic factor at several time points in the BFM study (ALL-BFM 90) as well as in the EORTC study. The aim of our investigations was the detection of MRD at the end of induction therapy within the COALL studies which is different from the above studies. In the COALL studies, therapy starts with a 1 week DNR prephase (24 h infusion on day one) and i.th. MTX. Induction therapy consisted of 3 drugs over a period of 4 weeks (Prednisolone, Vincristine and Daunorubicin), asparaginase is given later in consolidation. At the end of induction therapy, bone marrow was obtained for cytomorphologic and molecular analysis. PATIENTS AND METHODS: We investigated bone marrow samples from 76 patients. All patients were in morphologic remission at the end. of induction therapy. For MRD analysis, DNA was isolated from bone marrow mononuclear cells. Clonal T-cell-receptor (TCR) or immunoglobulin gene (IgH) rearrangements were identified by PCR. Monoclonal products were either sequenced directly (TCR) or after excision from high resolution agarose gels. Subsequently patient-specific oligonucleotides for allele-specific PCR were generated. PCR analysis was performed with 1 microgram DNA for each reaction within a semiquantitative matter. This method reached sensitivities down to 10(-5). RESULTS: Eighty-four percent of the analysed samples were MRD positive at the end of induction therapy. 20 out of 76 patient samples (26%) were highly positive (> or = 10(-2)), 28 patients had levels of about 10(-3) (37%), 16 had levels around 10(-4) (21%) and 12 patients had no detectable residual cells (16%). All analysed 15 T-ALL patients had detectable residual disease at this timepoint. Until now, 5/20 patients with very high MRD level at the end of induction therapy suffered a relapse. DISCUSSION: Patients with very high MRD level at the end of induction therapy showed an elevated risk of relapse, but the predictive value is much poorer than for example in the BFM 90 MRD-study. We suggest, that a high MRD level at this timepoint results from a different induction therapy compared to the BFM 90 study. In the COALL studies asparaginase is given only after induction therapy to decrease the risk of thrombosis. We would like to conclude that this differences were compensated later during therapy as the event free survival of both studies is similar. In conclusion, an optimal information from MRD studies is strongly associated with the given therapy. Therefore we initiated an additional MRD time-point after the first chemotherapy block in consolidation.

[Nosocomial colonization and infection by multiresistant Enterobacter cloacae strains on a pediatric oncological unit]. / Nosokomiale Kolonisation und Infektion durch multiresistente Enterobacter cloacae-Stämme auf einer onkologischen Kinderstation.

A multiresistant E. cloacae strain spread during a six month period in a paediatric oncology ward amongst nine children, who had different tumors and malformations. Three children who had shared a room were especially affected. E. cloacae was isolated 122 times from the children with tumors and five times from their environment. Specimens from which the bacteria were isolated, included blood cultures, catheter tips, wound swabs, drains, skin and mucous membranes from most parts of the body. The majority of the E. cloacae strains were resistant to ampicillin, mezlocillin, piperacillin, azlocillin, doxycycline and cephalosporins of the second and third generation and sensitive to imipenem, aminoglycosides and quinolones. The antimicrobial resistance patterns of the E. cloacae strains from the paediatric oncology ward were compared to those isolated from other wards in the hospital. E. cloacae isolates from the intensive care unit had a reduced sensitivity to beta-lactam antibiotics, whereas the isolates from the other wards were, with the exception of ampicillin, sensitive to beta-lactam antibiotics. The analysis of the E. cloacae strains from the paediatric oncology ward revealed the same antimicrobial resistance pattern, bacteriocin type, RFLP-type and an identical enzyme and whole cell profile. Isolates from other wards showed considerably deviating patterns. The systematic registration and isolation of patients, colonized or infected with multiresistant E. cloacae strains, together with infection control methods, lead to a significant reduction in infections.

[On the respiration analeptic effect of fominoben HCl after administration of pethidine/promethazine (author's transl)]. / Uber die atemanaleptische Wirkung von Fominoben-HCl nach Pethidin/Promethazin-Gabe.

The respiratory stimulatory effect of 3'chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)benzanilide hydrochloride (fominoben, Noleptan, PB 89) on the respiratory-depressing effect of pethidine/promethazine was investigated. In addition a double blind study was carried out on 36 patients with fominoben or placebo after pethidine/promethazine. To evaluate respiratory function the vital capacity, Tiffeneau-value, volume of inhaled air/s, maximum breathing capacity, as well as the blood gas values (pO2, pCO2 and pH according to Astrup) were measured. The results can be summarised as follows: 1. As was to be expected the combination pethidine/promethazine caused a deterioration in all parameters. This negative effect could be partially improved by fominoben. 2. A marked difference in the volume of inhaled air/s could be seen after fominoben in comparison to the placebo. The remaining differences were insignificant. 3. Pethidine/promethazine had, as had been expected, a significant effect on pain symptoms, but no analgetic effect could be shown for fominoben.