[Clinical research in the "acute and chronic leukemias"competence network ].

Goal of the network is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among all major groups in Germany that deal with the leukemias in research and in patient care. In practice, cooperation between clinical groups and scientists in research institutes is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation and also increase information transfer from top research institutions to clinical translation.

Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin's lymphoma.

This prospective study assessed the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the staging and possible consequential changes of treatment regimen in patients with Hodgkin's lymphoma (HL). A total of 88 consecutive patients with histologically verified Hodgkin's lymphoma underwent a PET scan in addition to conventional staging procedures. Treatment was based on the conventional staging only, and the results of the FDG-PET did not affect the treatment strategy.

Comparison of flow cytometry and laser scanning cytometry for the analysis of CD34+ hematopoietic stem cells.

Background: Characterization of hematopoietic stem cells (HSCs) by laser scanning cytometry (LSC) was compared with conventional flow cytometry (FCM). The method was evaluated for application in the development of advanced cell culture substrates that were supposed to support the ex vivo expansion of HSC. For this purpose, adherent HSCs were grown in culture on thin polymer films coated with reconstituted collagen I fibrils and subsequently analyzed by LSC.

P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate.

Imatinib (Glivec), STI571) is an intracellular acting drug that demonstrates high activity against BCR-ABL-positive chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). However, many patients, especially with advanced disease, develop drug resistance. Here, we show by a novel high-performance liquid chromatography-based method that intracellular levels of imatinib decrease in P-glycoprotein (Pgp)-positive leukemic cells.

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation--a retrospective analysis.

It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m2 FLU (n=45) or 8 mg/kg BU, 180 mg/m2 FLU and 40 mg/kg ATG (n=38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n=32) or a combination with either MTX or MMF (n=51).

CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid.

Imatinib mesylate (STI571) is a very effective treatment option for Ph(+) chronic myeloid leukemia (CML) in chronic phase. Secondary treatment failures have mostly been observed in patients with advanced stages of disease. We report the case of a patient who unexpectedly experienced blast crisis of the central nervous system although having achieved complete cytogenetic remission in the bone marrow.

Evaluation of STR informativity for chimerism testing--comparative analysis of 27 STR systems in 203 matched related donor recipient pairs.

Chimerism analysis has become a routine method to document engraftment and also for detection of residual disease. PCR-based procedures using STR analysis, especially commercially available multiplex assays, are frequently used. However, these assays have been optimized for forensic purposes and do not necessarily fulfil all needs for chimerism analysis.

Liquid chromatographic method for detection and quantitation of STI-571 and its main metabolite N-desmethyl-STI in plasma, urine, cerebrospinal fluid, culture medium and cell preparations.

An isocratic online-enrichment HPLC-assay was developed allowing for the simple and fast separation and quantitation of STI-571 and its main metabolite N-desmethyl-STI (N-DesM-STI) in plasma, urine, cerebrospinal fluid (CSF), culture media and cell preparations in various concentrations using UV-detection at 260 nm. The analytical procedure consists of an online concentration of STI-571 and N-DesM-STI in the HPLC system followed by the elution on a ZirChrom-PBD analytical column. Time of analysis is 40 min including the enrichment time of 5 min.

Pharmacokinetics and cellular uptake of imatinib and its main metabolite CGP74588.

Despite the remarkable clinical response rates to imatinib in the treatment of bcr-abl leukemic patients, pharmacokinetic data on this relatively novel substance are needed to improve our understanding of the emergence of resistance, the interindividual variations of clinical response and the clinical and biologic relevance of its main metabolite N-desmethyl-imatinib. We present here pharmacokinetic data obtained with a newly designed HPLC approach in 97 patients with chronic myeloid leukemia or acute lymphatic leukemia (ALL) under treatment with imatinib that allowed us to calculate the AUC (39.5 microg.

Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease.

Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkin's disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16 years, range: 11-19) received reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT) after failure of stratified first-line chemotherapy, involved-field radiotherapy, and salvage chemotherapy including autologous PBSCT (two patients). For conditioning, fludarabine was combined with busulfan (8 or 12 mg/kg) and additional cyclophosphamide (three patients), or without cyclophosphamide (two patients), or melphalan (one patient).

Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study.

Dendritic cells (DC) are professional antigen-presenting cells that are widely used in the experimental immunotherapy of cancer. For clinical use GMP-like protocols for the preparation of functionally active dendritic cells (DC) in large numbers and at high purity are needed. However, the currently available protocols have certain disadvantages.

HPC enumeration with the Sysmex XE-2100 can guide further flow cytometric CD34(+) measurements and timing of leukaphereses.

Background: The aim of this study was to evaluate whether HPC counts measured with the hematology analyzer can predict CD34+ levels in peripheral blood and in the apheresis product, as detected by standard flow cytometry. The main focus was the evaluation of HPC counts in poor mobilizers.

Methods: Progenitor cell quantification was performed measuring HPC counts provided by the Sysmex XE-2100 hematology analyzer and CD34+ counts obtained in parallel by flow cytometry.

Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib.

Imatinib has pronounced but brief antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We assessed the prognostic impact of pretreatment disease features and the early bone marrow (BM) response in 68 consecutive patients with Ph(+)ALL receiving imatinib salvage therapy. A complete hematologic or marrow response was achieved by 92% of patients with BM blasts below 5% on day 14, whereas 62.

Locally advanced small-bowel adenocarcinoma missed primarily by capsule endoscopy but diagnosed by push enteroscopy.

Wireless-capsule-endoscopy is a new painless method that is able both to visualize the entire small bowel and to detect even small lesions. We report here the case of a patient in whom a locally advanced small-bowel adenocarcinoma was initially missed on capsule endoscopy, but was diagnosed by subsequent push enteroscopy. Capsule endoscopy was carried out in a 47-year-old patient with a history of obscure gastrointestinal bleeding, iron-deficiency anemia, and a lack of symptoms suggestive of stenosis.

Increased myelotoxicity of idarubicin: is there a pharmacological basis? Results of a pharmacokinetic and an in vitro cytotoxicity study.

Background: Clinical trials evaluating idarubicin (IDA) in acute myeloid leukemia, multiple myeloma and non-Hodgkin's lymphoma (NHL) have provided some evidence for an increased myelotoxicity of IDA compared to other anthracyclines. IDA is known to be less sensitive towards multidrug resistance mediated by P-glycoprotein (P-gp). This phenotype is a major impediment to successful antineoplastic treatment, but P-gp is also expressed on hematopoietic stem cells (HSC).

Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation in myeloid diseases.

Within the past years, reduced or modified doses of chemotherapy or radiotherapy have been widely studied for conditioning before allogeneic hematopoietic cell transplantation in patients with myeloid leukemia not eligible for conventional transplantation. The main goal was to reduce the substantial treatment-related mortality in this patient population while preserving the potential curative graft-versus-leukemia effect. This review summarizes results of published trials using reduced-intensity conditioning (RIC) in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and myelofibrosis.

ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML).

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188).

Imatinib in Philadelphia chromosome-positive chronic phase CML patients: molecular and cytogenetic response rates and prediction of clinical outcome.

Previous clinical trials with the tyrosine kinase inhibitor imatinib in chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia (CML) resulted in 95% of hematologic and 60% major cytogenetic remissions in patients who failed a previous interferon-alpha-containing regimen. In an identical clinical trial setting with 39 chronic-phase CML patients we achieved comparable cytogenetic response rates after a median follow up of 30.1 weeks, with an almost identical toxicity profile.

Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group.

Purpose: To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL).

Patients And Methods: Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15).

Normal intrinsic Th1/Th2 balance in patients with chronic phase chronic myeloid leukemia not treated with interferon-alpha or imatinib.

Background And Objectives: CD4+ T helper cells are an integral part of effective immune responses against various malignancies; however in tumor-bearing patients they are frequently functionally unresponsive. T helper cells of patients with chronic myeloid leukemia (CML), analyzed as part of mononuclear cell fractions, show a loss of signaling molecules, a compromised Th1 cytokine production and a shift towards a non-productive Th2 state. The underlying mechanism is unknown and may involve intrinsic T cell defects as well as indirect effects mediated by leukemia or antigen-presenting cells.

Population pharmacokinetics of oral busulfan in children.

Purpose: To characterize the population pharmacokinetics of oral busulfan in 48 children including pooled data from three transplantation centres with the aim of estimating the variability in the kinetics of busulfan and to identify covariates that could be used for dose calculation.

Methods: A total of 508 plasma samples from 250 administrations (mean 9 samples per patient over 4 days of treatment) were collected from 48 children receiving busulfan orally every 6 h. The dosing varied between 13 and 20 mg/kg with seven patients receiving a dose of 600 mg/m(2).

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20).

[Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma].

Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma. HISTORY AND CLINICAL FINDINGS: A 39-year-old woman was admitted to our department of gastroenterology with recurrent epigastrical pain. Ten years previously the diagnosis of von Hippel-Lindau (VHL)-syndrome has been established.