D Hoelzer

..The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated...

..The primer sequences were based on highly interspecies-conserved virus genome regions. We used this PCR to detect Deltaretroviruses in samples from adult patients with a variety of rare T-cell neoplasms in Germany...

..Subtype adjusted therapy, rational treatment decisions based on MRD and new, 'causative' treatment approaches are highlighted as the most promising perspectives for future improvement of treatment results in adult ALL...

..Prognostic factors are published for T-ALL but not for T-LBL. MRD may guide further treatment strategies in T-ALL and probably also in T-LBL as indications for a SCT or for the evaluation of novel, particularly T-cell-specific, drugs...

..Mediastinal recurrence was the major obstacle and further improvement by intensification of chemotherapy, increased dose of mediastinal irradiation (36 Gy), and extended indications for stem cell transplantation seem to be required...

..However, several details for an optimal treatment approach e.g. the required level of antigen expression, timing, schedule, dosage and stage of disease still need to be defined...

..However, several details for an optimal treatment approach, such as the required level of antigen expression, timing, schedule, dosage, and stage of disease, still need to be defined...

..This study therefore examined whether the impaired signaling in MDS and AML cells includes alterations of c-mpl itself or postsignaling events...

..To determine whether TGF-beta(1) interferes directly with TPO-induced signal transduction in hematopoietic cells, we compared the regulatory effects in the TPO-responsive cell lines Mo-7e and HEL...

..In contrast, proliferation of NK92 cells is not affected by MAPK p44erk-1 and p42erk-2...

..This case illustrates the ability of imatinib to induce sustained hematologic and molecular remissions in some patients relapsing with advanced stage CML after alloSCT...

..Thus, these MRD parameters may guide timing and intensity of therapeutic modifications...

..Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients...

..Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT...

..CNS prophylaxis is necessary and may enhance the antileukemic activity of imatinib and IFN-alpha...

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..Cotransfection of STAT5 resulted in increased induction of the IL-18 promoter in the U937 and THP-1 cells...

..Moreover, the prevalence of pre-existing, clinically relevant TKD may have been underestimated in tyrosine kinase inhibitor-naïve patients with Ph+ ALL...

..Thus, in MDS-derived AML, altered responses to TGF beta may be due to defects downstream of SMAD2 and may involve MAPK activation...

..6484, P=0.0121). In conclusion AC133 expression is closely related to CD34 expression in AML. In leukapheresis products AC133 provides an additional marker for selection of PBPC autografts in AC133- AML...

..In conclusion, HRU is a useful tool for detecting acute bowel GvHD even before clinical symptoms. Moreover, HRU and CDI can be applied to define the severity of aGvHD and to identify patients with a poor prognosis...

..In conclusion, our risk-adapted strategy produced encouraging results in SR patients. Early response to therapy is a strong prognostic factor that predicts the probability of CR and long-term outcome...

..The synergistic lymphocytotoxic effect of 2-CdA combined with doxorubicin or mitoxantrone may be relevant for new treatment approaches...

..These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL...

..These results indicate that hypermethylation of cell cycle control genes in MDS may occur late during the differentiation of myelodysplastic stem cells...

..Hepatosplenic gd T-cell lymphoma is a rare entity of peripheral T-cell lymphomas. We characterized in detail the first case of hepatosplenic gd -T-cell lymphoma following acute myeloid leukemia...

..In the future however an earlier identification of high risk patients (after 4 months) will be attempted...

..The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols...

..The reduction of treatment costs by reducing the total G-CSF dose may be important in future treatment with this hematopoietic growth factor...

..High levels of IL-18 expression in RA joints are contrasted by reduced IL-18 expression in RA peripheral blood mononuclear cells (PBMC). Here, we investigated a putative IL-18 regulating role of corticosteroids...

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..However, inhibition of the PI-3K pathway by LY294002 did not impair TF-1 cell migration in our three-dimensional model system...

..04). In conclusion, treatment with TFN alpha and ATRA did not result in improved megakaryocytopoiesis as assessed by in-vitro cultures. On the contrary, low-dose IFN alpha appears to suppress cell proliferation as well as MK development...

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..The presence of a CHK2 mutation in MDS highlights the importance of alterations of cell cycle checkpoint genes in this disease...

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..We report herein the identification and characterization of HDAC3, a yeast RPD3 ortholog in the mouse. Studies on murine HDAC3 may yield important insights on the understanding of myeloproliferative disease in humans...

..However, our search for mutations in this gene did not identify somatic mutations in MDS. Our findings are consistent with the possible existence of an as-yet unknown tumor suppressor gene in this region that is altered in MDS...

..84. Fluorescence in situ hybridization analysis localized the human HDAC5 gene to chromosome 17q21, a region which is characterized by frequent gains and losses of chromosomal material in several types of cancer...

..5 pg/ml). In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA. The serum TNF alpha levels were unchanged during treatment with amifostine in RA patients...

..In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary...

..To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas...

..Since HDAC3 carries strong potential to be a tumor suppressor gene, we report herein its exact position between the CD14 and GRIA1 genes within the 5q31.1 subband...

..The objective of this multicenter study was to evaluate the activity of cladribine in mantle-cell lymphomas as first-line therapy or in first relapse using an intermittent two-hour infusion of cladribine...

..We conclude that therapy with ATRA, IFNalpha, and G-CSF is effective in approximately 35% of low-risk MDS patients (in this study: six of 17) and may induce complete remission in individual cases...

..Neutralization experiments revealed differential contributions of Flt3 ligand and thrombopoietin to the support of total cell and CFC expansion by Sl/M2 and Sl/Sl stromal feeders...

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..We conclude that monotherapy with thalidomide might be an alternative maintenance strategy with limited response duration for patients with primary PCL in impaired general condition...

..Retrospective analysis of the evaluable parameters (CHr, sTrfR, and ZnPP) revealed no additional benefit for predicting or monitoring IDE in this setting, although the one or other may be advantageous in other therapeutic situations...

..Due to the considerable bureaucratic effort and increased costs, only few large multicenter trials could thereafter be initiated and a substantial disadvantage for independent academic research becomes clearly evident...

..Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance...

..The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT...

..As the remaining open questions are resolved, clinical benefits may be achieved consistently and with a favorable cost benefit ratio...

..Disease status at time of transplantation is an important determinant of DFS and TRM...

..To search for RA specific processes among T cell accumulation, T cell activation, or cytokine expression in CD4+ and CD8+ synovial fluid (SF) T cells...

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..Taken together, we describe an approach that allows the easy and reproducible identification of protein ligands on the basis of a whole-genome expression analysis...

..5%) with predisposing DQ alleles alone (OR = 0.12, 95% CI: 0.02-0.72, p = 0.004). These results demonstrate a protective role of (70)DERAA(74)-positive DRB1 alleles against disease severity among RA patients...

..Thus, bcl-2 and wt1 mRNA expression are associated with response and long-term outcome in AMLs. The coexpression of these genes allows determination of prognostic groups with high predictive value for overall and disease-free survival...

..CONCLUSIONS: Treatment with VPA/ATRA results in transient disease control in a subset of patients with AML that has evolved from a myeloproliferative disorder but not in patients with a primary or MDS-related AML...

..While reviewing these molecular alterations this article moreover focuses on the impact of new therapeutic agents, which specifically exploit the knowledge of the molecular characteristics of malignant hematopoetic cells...

..These data provide further evidence for a functional hierarchy in the human HSC compartment and suggest a link between telomere length and proliferation capacity of individual HSC clones...

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..Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated...

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..Our data suggest a differential effect of VPA on the small population of AML progenitor cells and the bulk of aberrantly differentiated blasts in the majority of AML samples tested...

..In conclusion, functional PTP1B is involved in STI571-induced growth and cell cycle arrest, apoptosis, and differentiation, and attenuation of PTP1B function may contribute to resistance towards STI571...

..Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy...

..This provides a rationale for the frontline use of kinase inhibitors active against these BCR-ABL mutants...

..Arsenic induces high rates of CR and CMR followed by a long relapse-free survival (RFS). Here we compared the effects of ATRA and arsenic on PML/RARalpha-positive stem cell compartments...

..Future prospects for improvement of treatment results in LBL include intensification of chemotherapy, definition of prognostic factors, evaluation of minimal residual disease and SCT in high-risk patients...

..Our data suggest that lineage-specific methylation-associated gene silencing of survivin, CHK2, and WT1 in MDS hematopoietic precursor cells may contribute to the MDS-specific phenotype..

..Outcome may be improved compared to patients treated with CHOP-based regimens. In the era of HAART, more intensive chemotherapy regimens should be considered in patients with highly aggressive lymphomas...

..As a result of the study, as of spring 2006, salvage treatment in the ongoing GMALL trial is intended to be started at the time of recurrence of quantifiable MRD...

..Details of these regimens - required level of antigen expression, timing, schedule, dosage and stage of disease - remain to be defined...

..Based on the results, we have established and tested a novel PCR method for simplified detection of the NUP214-ABL1 fusion gene...

..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...

..We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile...

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..This study provides the first basis for establishing novel SrcK-I as weapons in the arsenal against lymphoma cells...

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..Upon a proapoptotic stimulus such as serum withdrawal Daxx is unable to maintain its influence on expression levels of p53, Bax, IAPs and the procaspase-8, -10 and -7...

..SNPs of PDGFR genes do not appear to play a role in patient's susceptibility to clinically severe edema formation during treatment with STI571...

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..Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis...

..The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies...

..In conclusion, SCFA up-regulate IL-18 protein expression in IEC, suggesting a potential regulatory contribution of these luminal constituents to T cell mediated inflammatory and neoplastic intestinal conditions...

..Optimal treatment regimens with bendamustine in the treatment of low-grade NHL are yet to be defined, but results obtained to date indicate that further studies are warranted...

..The actions of the combination of bendamustine and rituximab on ex vivo B-cell chronic lymphocytic leukemia cells and the DOHH-2 cell line, derived from CD20-positive lymphoma cells, are discussed in this article...

..3 kDa and an isoelectric point of 6.41. Fluorescence in situ hybridization analysis localized the human HDAC9 gene to chromosome 7p21, a region which has been associated particularly with the pathogenesis of gynecological tumors...

..While sodium butyrate or TSA stimulated the 108-bp IL-18 minimal promoter, valproate failed to activate it, indicating that valproate may use a distinct mechanism from sodium butyrate and TSA to activate IL-18 gene expression...

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