GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 8 ( 2018-1-12)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606827-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Blood, American Society of Hematology, Vol. 105, No. 12 ( 2005-06-15), p. 4893-4894
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3248-3248
    Abstract: Abstract 3248 Poster Board III-1 The polyspecific organic cation transporter OCT1 (SLC22A1) exhibits broad substrate specificity and facilitates the intracellular uptake of imatinib mesylate (IM). The contribution of OCT1 to the clinical outcome of CML patients treated with IM remains controversial. The aim of this study was to compare OCT1 transcript levels in different normal cell populations, to examine the effect of BCR-ABL1 oncoprotein and IM on OCT1 expression, to investigate the predictive value of OCT1 levels and to determine whether OCT1 SNPs in CML patients correlate with altered IM response and sensitivity. We found that OCT1 mRNA expression was higher in normal PMNs than in normal MNCs (p 〈 0.0001). In CML, total WBC OCT1 transcript levels were significantly higher in CCyR samples than in patient samples collected at diagnosis (p 〈 0.0001). There was no significant difference between OCT1 expression at the time of cytogenetic remission in CML patients (n=60) compared with OCT1 expression in normal subjects (n=21) suggesting an inhibitory effect of Bcr-Abl1 rather than a drug inducing effect of IM. Furthermore, OCT1 transcript levels at diagnosis prior to IM therapy could predict for both a 3- and 4-log reduction in Bcr-Abl1 transcripts following IM therapy. We investigated the association of 7 previously described non-synonymous SNPs of SLC22A1 with respect to IM response in 89 CCyR responders and 44 non-responders. SNPs P283L, R287G and C88R were not subjected to statistical analysis as the frequency of polymorphisms in our cohort at these respective loci was too small. For the remaining 4 screened SNPs (rs622342, R61C, P341L and G401S), no relationship could be found between allele frequency and pre-treatment OCT1 transcript levels (n=60). This finding is expected, given that the locations of these SNPs do not involve the promoter region of SLC22A1. We were however able to demonstrate a correlation between response to IM and SNP G401S. Though numbers were small, heterozygotes for this allele had a greater probability of achieving a 3-log reduction in Bcr-Abl1 transcript levels (p=0.015). Although this genotype has been described previously as a loss of function polymorphism, we showed the opposite to be true in CML patients on IM therapy. This finding may suggest that first-pass extraction of orally administered IM by liver metabolizing cells, could be diminished and so lead to a higher serum drug concentration and hence a greater intensity and duration of action. Alternatively, this could highlight the insignificant contribution that genetic variation of SCL22A1 plays in the outcome of patients with CML. In conclusion, OCT1 transcript levels vary in different cells types, are low in untreated CML patients but return to ‘normal' after successful treatment with IM. The clinical relevance of SLC22A1 SNPs warrants further study. Disclosures: Novartis: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2147-2147
    Abstract: Abstract 2147 Poster Board II-124 In the era of novel therapeutic agents, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remains an integral component of treatment for multiple myeloma (MM), with a proportion of patients undergoing more than one ASCT during the course of their disease. Therefore, the choice of new drug combinations for induction therapies must take into consideration the requirement to collect a sufficient number of stem cells, which is also reflected in a recently published consensus perspective of the International Myeloma Working Group. The immunomodulatory drug Lenalidomide and the alkylating agent Melphalan have a substantial impact on stem cell mobilization, but the effect of induction therapies containing either Thalidomide or Cyclophosphamide on the stem cell collection yield is negligible. We considered the possibility that the combination of Cyclophosphamide and Thalidomide, which is widely used as an induction regime particularly in the UK as part of the CTD regime (with Dexamethasone), could have an additive impact on the stem cell pool and cause mobilization failures. We carried out a retrospective analysis of the outcome of peripheral blood stem cell mobilizations in MM patients performed at our institution over a four-year period in patients who had received CTD (n=55), and compared them with a control group of patients (n=56) who had received VAD (Vincristine, Doxorubicin, Dexamethasone; n=30) or Z-Dex (Idarubicin, Dexamethasone; n=26) during the same period. There were no differences between the CTD and control group in terms of age, MM subtype, disease stage, or remission status at the time of stem cell mobilization. All mobilizations were performed with Cyclophosphamide (4g/m2) and G-CSF (5-10μg/kg). Apheresis was attempted when the peripheral blood CD34 count was 〉 10 × 103/ml, and the standard harvest target was 4 × 106 CD34+ cells/kg, with a minimal target of 2 × 106 CD34+ cells/kg. The total number of CD34+ cells harvested was substantially lower in the CTD group (5.2 vs. 9.7 × 106/kg, p=0.002), and a higher number of patients in the CTD group underwent more than one apheresis procedure (52.8% vs. 32.1%, p=0.012). The number of CD34+ cells harvested on the first day of apheresis and per apheresis procedure were also lower in the CTD group (2.8 vs. 7.3 × 106/kg, p=0.002; 2.6 vs. 6.7 × 106/kg, p=0.002). More patients in the CTD group failed to achieve both the standard (36.4% vs. 16.1%, p=0.021) and minimal (19.2% vs. 5.4%, p=0.036) stem cell harvest target. The failure rate on the first day of apheresis was also higher in the CTD group both for the standard (56.3% vs. 28.6%, p=0.003) and the minimal target (36.7% vs. 16.1%, p=0.041). There was no difference in stem cell yield between the VAD and Z-Dex groups. Age and number of induction chemotherapy cycles did not have an impact on mobilization failure in the entire cohort or the CTD group alone. In the CTD group, 18% of patients underwent re-mobilization with Etoposide (1.6g/ m2) and G-CSF (n=8), or with Plerixafor (240μg/kg) and G-CSF (n=2), which was successful in all patients. These results demonstrate that the CTD induction regime results in a high rate of stem cell mobilization failures, which is associated with the requirement for an increased number of apheresis and re-mobilization procedures. The observations provide novel evidence that drugs with no previously demonstrated significant effect on stem cell mobilization can have a considerable negative impact on the stem cell yield when used in combination. The possible benefit of new drug combinations has to be balanced against the increase in cost, the potentially higher rate of complications, and delays or failures to progress to ASCT resulting from impaired stem cell mobilization. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4348-4348
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4348-4348
    Abstract: Introduction: Haemopoietic stem cell transplantation (SCT) is a potentially curative treatment for haematological disease. Relapse, second malignancies, cardiovascular events, infection and GVHD-related disease are all established causes of death in the first 10 years post-SCT. Significant morbidity has also been described including cardiac risk factors, cardiovascular disease, malignancy, endocrinopathies and infertility. Although many of these complications are well documented in the first 5-15 years of follow-up, few studies have addressed mortality and morbidity in patients surviving longer than 15 years. Methods: In this single centre study, the causes of death and cumulative burden of morbidity were investigated for patients who survived a minimum of 15 years after allogeneic SCT. Survival status was verified by a) confirming recent attendance in clinic b) review of National Health Service data which records mortality statistics for patients registered with a family doctor (GP) in the UK. Causes of death were sought from hospital records, GP records or death certificates. Data on second malignancies (excluding non-melanoma skin cancer) and cardiac disease were documented from patient notes. Use of medication at 15, 20, 25 and 30 years was collected as a surrogate indicator of the cumulative burden and nature of morbidity. Results: 178 patients were identified who were known to be alive and in the UK 15 years post-SCT. The median follow up from this point was 7.4 years (range 0-20). The majority (170/178) received TBI conditioning with a median dose of 12Gy (range 10-14.4). The median age 15 years post-SCT was 48 years (range 20-74). Original disease was CML in 152 (85.4%) and acute leukaemia in 18 (10.1%). Probabilities of survival at 20, 25 and 30 years post-SCT were 90.0% (CI 85.4-94.6), 79.5% (72.2-86.7) and 73.5% (63.9-83.1). 32/178 (20%) of the 15-year survivors died, at a median of 19.1 years (range 15.1-30.6) post-SCT. Causes of death were available for 26/32 (81%) patients: eleven were due to infection, ten attributed to second malignancy, 2 cardiac, 2 respiratory and 1 was due to acute pancreatitis. Of infective deaths, 9 were from pneumonia and 8/9 of these were associated with underlying lung disease, organ failure or immune suppression. No patient died from primary disease relapse. Second malignancies affected 35/178 (20%) patients with 9 developing them prior to 15 years. The probabilites of having a second malignancy at 15, 20, 25 and 30 years post-SCT were 5.6% (95% CI 2.2-9.0), 17.6% (11.0-23.2), 29.1% (18.9-39.3) and 42.7% (26.1-59.3). Seven patients developed multiple second malignancies. From a total of 43 malignancies the most common tumour sites were breast (n=8) and oral cavity (n=5). Development of second malignancy was associated with significantly reduced survival compared to patients who did not have a second malignancy (p=0.001). Cardiovascular disease affected 14.7% of patients with cumulative incidences of 5.7% (1.7-9.7), 8.2% (3.2-13.2) and 22.3% (12.1-32.5) by 15, 20 and 25 years post-SCT respectively. Fifteen years post SCT, the use of anti-hypertensive. lipid lowering medication and (in women) anti-platelet agents were higher than the use in the gender matched normal population (Table 1). Use of these drugs increased significantly further (p 〈 0.05) between 15 and 30 years to 38.5%, 48.7% and 15.4% respectively. Conclusion: Our data indicate that deaths after 15 years in this group of patient are most frequently due to second malignancy or else pneumonia in a setting of post-transplant complications. There were no deaths due to relapse. The burden of morbidity increased substantially between 15 and 30 years and this warrants lifelong specialist follow up. Table 1. comparison of medication use between study group and age matched population statistics from *HSCIC (UK Health and Social Care Information Centre, Use of prescribed Medicines 2013) 15years post SCT Age matched population data* 25 years post SCT Age matched population data* MALE PATIENTS Median age (range) 47.4 years (29-74)n=100 51.1 years (39-65) n=25 Lipid lowering drugs 15% 11% 52.6% 11% Anti-hypertensive agents 30% 12% 36.8% 12% Anti-platelet agents 5% 4% 15.8% 4% FEMALE PATIENTS Median age (range 48.2 years (20-73) n=78 56.2 years (31-75) n=33 Lipid lowering drugs 23.3% 6% 42.9% 17% Anti-hypertensive agents 35% 10% 42.9% 22% Anti-platelet agents 5% 2% 14.3% 6% Disclosures Apperley: BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ARIAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Blood, American Society of Hematology, Vol. 116, No. 25 ( 2010-12-16), p. 5497-5500
    Abstract: We analyzed a cohort of 26 patients with chronic myeloid leukemia who had failed imatinib and a second tyrosine kinase inhibitor but were still in first chronic phase and identified prognostic factors for response and outcomes. The achievement of a prior cytogenetic response on imatinib or on second-line therapy were the only independent predictors for the achievement of complete cytogenetic responses on third-line therapy. Younger age and the achievement of a cytogenetic response on second line were the only independent predictors for overall survival (OS). At 3 months, the 9 patients who had achieved a cytogenetic response had better 30-month probabilities of complete cytogenetic responses and OS than the patients who had failed to do so. Factors measurable before starting treatment with third line therapy and cytogenetic responses at 3 months can accurately predict subsequent outcome and thus guide clinical decisions.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: Blood, American Society of Hematology, Vol. 120, No. 25 ( 2012-12-13), p. 5087-5088
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Blood, American Society of Hematology, Vol. 116, No. 12 ( 2010-09-23), p. 2033-2039
    Abstract: Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1+ (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1+ compared with KIR3DS1− was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1+ in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1+KIR3DL1+HLA-Bw4− had a significantly shorter PFS than patients who were KIR3DS1−, translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR–human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: Blood, American Society of Hematology, Vol. 102, No. 3 ( 2003-08-01), p. 1064-1069
    Abstract: Interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK/osteoprotegerin (OPG) plays a dominant role in osteoclast activation and possibly in plasma cell survival in multiple myeloma (MM). We measured soluble RANKL (sRANKL), OPG, and bone remodeling markers in 121 patients with newly diagnosed MM to evaluate their role in bone disease and survival. Serum levels of sRANKL were elevated in patients with MM and correlated with bone disease. The sRANKL/OPG ratio was also increased and correlated with markers of bone resorption, osteolytic lesions, and markers of disease activity. The sRANKL/OPG ratio, C-reactive protein (CRP), and β2-microglobulin were the only independent prognostic factors predicting survival in multivariate analysis. We generated a prognostic index based on these factors that divided our patients into 3 risk groups. The low-risk group had a 96% probability of survival at 5 years, whereas the intermediate-risk and the high-risk groups had probabilities of survival of 52% and 0%, respectively. Not only do these results confirm for the first time in humans the importance of sRANKL/OPG in the development of bone disease, they also highlight the role of this pathway in the biology of plasma cell growth as reflected by its influence on survival.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2003
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: British Journal of Haematology, Wiley, Vol. 122, No. 3 ( 2003-08), p. 424-429
    Type of Medium: Online Resource
    ISSN: 0007-1048
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2003
    detail.hit.zdb_id: 1475751-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...