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  • 1
    Online-Ressource
    Online-Ressource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 8 ( 2012-03-10), p. e95-e96
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 8 ( 2012-03-10), p. e95-e96
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2012
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    SAGE Publications ; 2008
    In:  Annals of Pharmacotherapy Vol. 42, No. 12 ( 2008-12), p. 1882-1886
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 42, No. 12 ( 2008-12), p. 1882-1886
    Kurzfassung: Despite the high prevalence of headache and migraine in the general population, many people do not receive adequate medical attention and treatment. Case Summary: A 29-year-old woman was diagnosed with Bcr-abl+ acute lymphoblastic leukemia, and treatment was initiated with chemotherapy and imatinib 800 mg daily. Following imatinib initiation, a gradual decrease in serum sodium level was noticed. Prolonged aplasia and neutropenic fever prompted discontinuation of therapy for 4 weeks. Following the patient's recovery, complete remission was achieved and monotherapy with imatinib 800 mg daily was restarted; however, hyponatremia recurred a few days later. The clinical findings and laboratory workup were compatible with the diagnosis of SIADH, which was attributed to high-dose imatinib. Fluid restriction and imatinib dosage reduction (to 600 mg/day) restored sodium levels. According to the Naranjo probability scale, this adverse reaction was probably associated with imatinib. Discussion: Imatinib emerged as the first tyrosine kinase inhibitor to enter everyday clinical practice for the treatment of Ph+ leukemias. Due to its molecular specificity, imatinib lacks the broad cytotoxicity of conventional chemotherapy. Inhibition of kinases in normal tissues accounts for many of imatinib's adverse reactions. To our knowledge, this is the first reported case of imatinib-induced SIADH. Conclusions: We recommend monitoring for SIADH if a patient receiving high-dose imatinib develops hyponatremia.
    Materialart: Online-Ressource
    ISSN: 1060-0280 , 1542-6270
    Sprache: Englisch
    Verlag: SAGE Publications
    Publikationsdatum: 2008
    ZDB Id: 2053518-1
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4116-4116
    Kurzfassung: Abstract 4116 The main prognostic determinant of the outcome of allogeneic stem cell transplantation (allo-SCT) for acute myeloid leukemia (AML) is disease phase at transplant while the relevance of the assessment of minimal residual disease (MRD) at transplant has not been elucidated. Although molecular markers are highly sensitive for the detection of MRD, they are available in only half of AML cases to date. On the other hand, multiparametric flow cytometry (MFC) offers the feasibility of MRD assessment in virtually all patients. We retrospectively studied the influence of pre-transplant MRD status by MFC on the outcomes of patients with AML in relation to other known prognostic factors. From 01/2003 to 12/2010, 102 AML patients (male/female; 58/44), aged 15–64 (median; 42) years, received allo-SCT in our center at first (CR1, N=69) or subsequent (CR≥2, N=33) morphologic complete remission. Donors were HLA-compatible siblings (N=45), matched unrelated (N=34) or alternative (haploidentical relatives or unrelated cord blood; N=6 and 17, respectively). The conditioning regimen was myeloablative in 85 (83.33%), and reduced-intensity in 17 (16.67%) cases. Data on MRD assessment by four- or five-color MFC before transplant were available in 92 patients. MRD was defined as any percentage of cells with an aberrant antigen expression pattern compared to normal or regenerating marrow. Transplant outcomes associated with MRD in univariate and multivariate analysis were overall (OS) and disease-free (DFS) survival, relapse incidence, and non-relapse-related mortality (NRM). Prognostic parameters included in the statistical model were the following: age and gender of recipient or donor, interval from diagnosis to transplant, de novo versus secondary AML, CR1 versus CR≥2 at transplant, cytogenetic risk group (according to Intergroup ECOG/SWOG definition), recipient and donor cytomegalovirus (CMV) serostatus, donor type, conditioning regimen (myeloablative versus reduced-intensity), degree of HLA match, method of graft-versus-host disease (GVHD) prophylaxis, and the modified European Blood and Marrow Transplantation Group (EBMT) risk score (Hemmati et al, 2011). With a median follow-up of 47 (range, 6–98) months, OS and DFS were 54.2% and 51.72%, respectively. The cumulative incidence of relapse was 24.45%, and of NRM 23.82%. Eighteen out of 92 (19.57%) patients had MRD by MFC before allo-SCT. According to univariate analysis, the presence of MRD showed a negative association with OS (29.63% versus 63.17% at 4 years in patients with or without MRD, respectively, P=0.053) and DFS (28.52% in MRD-positive versus 59.74% in MRD-negative cases at 4 years, P=0.025, Figure 1). Presence of MRD correlated with higher incidence of relapse compared to MRD negativity (52.7% versus 15.8%, respectively, P=0.001) (Figure 2), but did not influence NRM. In multivariate analysis (Cox proportional hazards, backward stepwise selection), the parameters that remained independent adverse risk factors in terms of specific outcomes were: a) For OS: age and male gender of patient, alternative donor, unfavorable karyotype, CR≥2, and secondary AML, b) For DFS: presence of MRD (HR=3.2, P=0.009), CR≥2 (ÇR=3.1, P=0.005), reduced-intensity conditioning (HR=2.6, P=0.034), and unfavorable karyotype (HR=2.06, P=0.074), c) For relapse: presence of MRD (ÇR=3.83, P=0.003), and unfavorable karyotype (HR=3.55, P=0.007), and d) For NRM: age of recipient, CR≥2, and alternative donor. In conclusion, the presence of MRD by MFC before allo-SCT for AML is associated with a significantly higher risk of relapse and an inferior DFS, despite morphologic complete remission at transplant. Moreover, pre-transplantation MRD status has independent prognostic significance in addition to the disease phase, cytogenetic risk group, and intensity of the conditioning regimen. Prospective studies are warranted to examine if the adverse impact of MRD on the outcomes of allo-SCT can be reversed by immunologic manipulations aiming at augmenting graft-versus-leukemia (GVL) effect. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Hematological Oncology, Wiley, Vol. 36, No. 1 ( 2018-02), p. 174-181
    Kurzfassung: This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety‐five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty‐seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2‐16), and the median time to best response was the fourth cycle. Fifty‐seven patients achieved an objective response: twenty‐two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty‐six (27%) had progressive disease as their best response. At a median follow‐up of 11.5 months, median progression‐free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV ( P  = .005). Bulky disease ( P  = .01) and response to BV ( P   〈 .001) were significant for progression‐free survival, while refractoriness to most recent treatment ( P  = .04), bulky disease ( P  = .005), and B‐symptoms ( P  = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow‐up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.
    Materialart: Online-Ressource
    ISSN: 0278-0232 , 1099-1069
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2018
    ZDB Id: 2001443-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Transfusion and Apheresis Science, Elsevier BV, Vol. 46, No. 2 ( 2012-4), p. 173-180
    Materialart: Online-Ressource
    ISSN: 1473-0502
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2012
    ZDB Id: 2129669-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Transfusion and Apheresis Science, Elsevier BV, Vol. 46, No. 2 ( 2012-4), p. 181-188
    Materialart: Online-Ressource
    ISSN: 1473-0502
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2012
    ZDB Id: 2129669-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3596-3596
    Kurzfassung: Bortezomib has significant activity in multiple myeloma (MM). Its efficacy is increased with the addition of dexamethasone and doxorubicin in vitro, thus providing the rationale for combination regimens with these agents. The aim of this study was to evaluate the efficacy and safety of PAD regimen (bortezomib, doxorubicin, dexamethasone) in high-risk, newly diagnosed, MM patients and evaluate its effect on bone remodeling and angiogenesis. The inclusion criteria included newly diagnosed MM, ISS 2/3 disease or del13q detected by FISH. Patients received four 21-day cycles of PAD: bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11; dexamethasone 40 mg on days 1–4 and 8–11; bolus doxorubicin 9 mg/m2 on days 1–4. All patients received monthly zoledronic acid and prophylactic dose of co-trimoxazole and acyclovir. Following peripheral blood stem cell (PBSC) collection, eligible patients received high-dose melphalan with PBSC transplantation. Effect of PAD on angiogenesis was evaluated by measuring serum levels of VEGF, VEGF-A, angiogenin, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and basic fibroblast growth factor at baseline and on day 21 of cycle 4. Bone remodeling was studied by the measurement of serum indices: osteoclast stimulators [soluble RANKL, and osteoprotegerin (OPG)], bone resorption markers [C-telopeptide of collagen type-I (CTX), and tartrate resistant acid phosphatase-5b (TRACP-5b)] , and bone formation markers [bone alkaline phosphatase (bALP), and osteocalcin] at baseline and on day 21 of cycle 4. All above molecules were also measured in 22 healthy controls of similar age and gender. To-date, 23 patients (14M/9F, median age 60 years) completed 4 cycles of therapy: 12 (52%) had ISS stage 2 and 11 (47%) stage 3 disease. Del13q was detected in 12 patients. The majority of patients (n=12) had more than 3 lytic lesions and/or a pathological fracture in the plain radiography of the skeleton. The objective response rate was 95% (22/23 patients): CR 26%, vgPR 13% and PR 56%. Median time to response was 35 days. Grade 3/4 adverse events included infections (7 patients-30%; one died due to septicemia), lymphopenia (6-26%), thrombocytopenia (6–26%), neutropenia (4–17%), peripheral neuropathy (3–13%), fatigue (2–8%), and hyponatremia (2–8%). At baseline, MM patients had increased serum levels of CTX, TRACP-5b, OPG, angiogenin, and Ang-2 compared with controls (p & lt;0.01), while the ratio of Ang-1/Ang-2 was reduced. The administration of PAD resulted in a dramatic reduction of bone resorption markers (p & lt;0.01) and a borderline increase in bALP (p=0.09). PAD also produced a significant increase of Ang-1/Ang-2 ratio (p=0.006), which was normalized. No patient developed a skeletal related event during 4 cycles of therapy. Eight patients (34%) had a PBSC collection; the median number of CD34+ cells was 6.45x106/kg (range: 2.3-13x106cells/kg). In conclusion, PAD has significant activity in high-risk, newly diagnosed patients with MM, overriding del13q. This regimen reduces bone resorption and normalizes Ang-1/Ang-2 balance which is crucial for the process of angiogenesis in MM.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2007
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1844-1844
    Kurzfassung: The detection of concurrent JAK2V617F and BCR-ABL mutations is uncommon; an incidence of 2.5% is reported in the literature. Scarce data indicate that the coexistence of JAK2V617F mutation and BCR-ABL translocation may denote an adverse prognostic factor for CML. Recently, the occurrence of novel Calreticulin (CALR) mutations in JAK2/MPL unmutated ET or PMF was reported. To our knowledge, no CALR mutations have been described so far in the context of BCR-ABL positive MPNs. We present 3 cases with molecularly defined diagnosis of another type of MPN in addition to Ph+ CML, including one patient with the novel finding of a CALR mutation in conjunction with the BCR-ABLtranslocation, and we infer a possible mechanism for the emergence of a second MPN clone upon treatment of the initial MPN. A 32 yr old female was diagnosed in 1999 with ET on the basis of marked thrombocytosis in the absence of any underlying cause. She was treated with INF-α and subsequently with anagrelide. Six years later (2005) and while the CBC was normal, cytogenetic and molecular studies disclosed the presence of Ph1 chromosome in 4/20 metaphases and BCR-ABL transcripts (7.2% IS, e15a2). Imatinib was initiated and after 3 months CCyR and MMR were achieved. Due to an increasing platelet count one year later, a trephine biopsy was performed that was compatible with ET. Hydroxyurea (HU) was added to treatment. No JAK2V617F mutation was detected. Fifteen years after the initial presentation, a CALR exon 9 mutation was retrospectively detected in all available samples since diagnosis of CML. The mutant allele burden has remained stable during follow-up, while patient being in MR4 with regard to CML. A 50 yr old woman was diagnosed with PV in 1998. Cytogenetic studies were normal and BCR-ABL was undetectable. JAK2V617F homozygous mutation was present on retrospective testing. A complete hematologic remission was achieved with phlebotomy and HU. Ten years later, re-evaluation due to an increasing WBC disclosed the presence of Ph1 chromosome in 20/20 metaphases and BCR-ABL transcripts (38.4% IS, e15a2). Interestingly, JAK2V617F was not detected. After 4 months of treatment with TKI plus HU, a 2-log BCR-ABL reduction was noted, while JAK2V617F was detected again at a heterozygous state. She received sequentially all 3 first available TKIs due to intolerance. Upon TKI treatment for 9 months, CCyR and MMR were achieved in parallel with emergence of JAK2V617F homozygosity. After achieving MR4 for more than 2 years, the TKI was discontinued and, 3 months later, the patient remains in MR4 with persistent JAK2V617F homozygosity. Due to splenomegaly and increased Hct, treatment with HU is continuously required. An 80 yr old female was diagnosed with chronic phase CML [Ph1+, BCR-ABL (35.5% IS, e15a2)]. She achieved mCyR and 1-log reduction of BCR-ABL levels after 6 months on imatinib. Due to imatinib failure, she was switched to nilotinib at 9 months. Two years after initial diagnosis, while CML was in MMR, an increase in Hct and platelets was noticed and JAK2V617F heterozygosity was detected. Retrospective analysis did not reveal JAK2V617F mutation at diagnosis and on the 3-month sample, while low level of mutant V617F allele was detected on the 6-month sample. Increasing levels of mutant versus wild type allele were detected in all subsequent samples. The patient was treated with phlebotomy, HU and ASA in addition to nilotinib. She died 4 years after initial diagnosis from an unrelated cause while in MR4 for CML and complete hematologic remission for PV. Despite these cases seem to be uncommon, they raise intriguing issues regarding the clonal origins of distinct molecular types of MPNs present in the same patient. They may also challenge the traditional hypothesis of evolution of one type of MPN to another. Instead of perceiving clinical and genetic features of second MPN as simple evolution of a precedent MPN, our cases suggest an alternative explanation based on pre-existence of two different MPN clones. Treatment for the initial MPN, especially with highly-efficient targeted agents (like TKIs for Ph+ CML) may facilitate the emergence of a second clone and vice versa. In conclusion, any divergent manifestations in a patient with MPN may warrant further investigation of genetic markers suggestive of an additional MPN entity. A high level of suspicion for the possibility of coexistence Ph+ and Ph- MPN may result in a more comprehensive treatment approach and optimal outcome. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2014
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3014-3014
    Kurzfassung: Abstract 3014FN2 Background: Allogeneic hematopoietic stem cell transplantation (SCT) is associated with iron overload and iron toxicity, especially in patients with myelodysplastic syndromes (MDS). Causes of this increased iron load are transfusions, ineffective erythropoiesis and, myelosuppressive therapy. Investigators found that iron toxicity (often using serum ferritin as a surrogate marker of iron burden) was associated with an adverse effect on non-relapse mortality (NRM) and overall survival (OS). As pre-transplant anti-leukemic treatment may lead to organ damage which may influence outcome after SCT, our study aimed to minimize the role of previous treatment toxicity by only including MDS patients who had not received intensive anti-leukemic treatment prior to SCT conditioning, allowing more insight in the role of iron toxicity in allogeneic SCT. A retrospective analysis of data from the EBMT registry was carried out after an additional survey within selected EBMT centers. Objectives: This report describes the effect of iron toxicity on OS, NRM and relapse during treatment with myeloablative (MAC) allogeneic SCT in previously untreated adults with MDS. Results: The Chronic Leukemia Working Party of the EBMT collected data of 201 adult patients with cytological proven MDS, according to the WHO classification, who received allogeneic SCT after myeloablative conditioning in 2000–2005. Data were available from 201 patients transplanted in 34 centers. All clinical variables were measured at time of transplantation. Fifty-nine percent of the patients were male (n=119). The median patient age was 49 years (range 18–70). Median time between diagnosis and transplantation was 8 months (range 0, 3–274). WHO classification at transplantation was RA/RARS/5q- 36% (n=72), RCMD 7% (n=15), RAEB-1 17% (n=34), RAEB-2 20% (n=39) and sAML 20% (n=41). A composite iron parameter based on the serum iron levels, transferrin saturation and serum ferritin levels prior to the SCT was used to define a high risk group with serum ferritin 〉 1, 500 ng/ml, and/or transferrin saturation 〉 80% and/or serum 〉 200 mg/l (low/intermediate/high 30% / very high 12% / missing 58%). Variables analyzed were WHO classification groups, iron load, amount of red blood cell (RBC) transfusions prior to SCT (≤20 RBC units 43% / 〉 20 RBC units 20% / missing 37%), age (≤50 years 58% / 〉 50 years 42%), cytogenetics (normal 31% / abnormal 46% / 23% not performed or missing), donor type (HLA id.Sibling 55% / Unrelated44%), match sex recipient-donor (male-female 23% /other 77%), time between diagnosis and transplantation (≤6 months 40% / 〉 6 months 60%), co morbidity (no 45% / yes 26%, missing 29%). Univariate analysis for OS showed a significant impact of WHO-classification (p=0.04), iron load (p=0.055) and, amount of RBC transfusions (p=0.02) but were not significant for age (p=0.23), cytogenetics (p=0.39), donor type (p=0.75), match sex recipient-donor (p=0.82), time between diagnosis and transplantation (p=0.30), and comorbidity scores (p=0, 11). The high risk iron load group show decreased 2-year OS (29% versus 59% in the low risk group) due to a combined higher relapse risk and NRM. Conclusion: These data show that disease stage has a significant impact on outcome. In addition a high number of RBC transfusions has a negative influence on OS, NRM and relapse. Iron load, when adjusted for transfusion numbers does not influence outcome. In our study with relatively low co-morbidity due to short interval between diagnosis and SCT (median 8 months) and the exclusion of patients who received anti-leukemic therapy prior to SCT the influence of co-morbidity on outcome was not significant. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 53, No. 11 ( 2012-11), p. 2302-2303
    Materialart: Online-Ressource
    ISSN: 1042-8194 , 1029-2403
    Sprache: Englisch
    Verlag: Informa UK Limited
    Publikationsdatum: 2012
    ZDB Id: 2030637-4
    Standort Signatur Einschränkungen Verfügbarkeit
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