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  • American Society of Hematology  (16)
  • Alimena, Giuliana  (16)
  • 1
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    Updating Long-Term Outcome of Intermittent Imatinib (INTERIM) Treatment in Elderly Patients with Ph+-CML
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 1794-1794
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1794-1794
    Abstract: BACKGROUND: The INTERIM study (ClinicalTrials.gov NCT 00858806) showed that in elderly ( 〉 65 years) Ph+ CML patients selected for a stable complete cytogenetic response (CCgR) lasting 〉 2 years, the policy of intermittent imatinib treatment (one month on/one month off) may affect the markers of residual disease (CCgR and major molecular response, MMR or MR3.0), but not the clinical outcomes (overall survival and progression-free survival) (Russo D et al, Blood 2013; 121(26):5138-44). AIMS: To update the results of the INTERIM Study, with a follow up ≥ 5 years. METHODS: After 4 years of follow up, patients continouing INTERIM treatment were monitored with peripheral blood RT-Q-PCR every 3 months according to the ELN-2013 guidelines. RESULTS: At 48thmonth, out of 76 patients enrolled in the INTERIM study, 13 (17%) had lost CCgR and MMR, 14 (18%) had lost MMR only and 50 patients (75%) continued INTERIM. The patients who had lost CCgR and/or MMR resumed imatinib continuously and all of them regained the CCgR and the MMR, within 3 to 12 months. No patient progressed to accelerated or blastic phase, or developed clonal chromosomal abnormalities in Ph+ cells, or BCR-ABL mutations. No patient complained of new or more severe side effects during the months “on”. After a follow up ≥ 5 years, 45/76 (59%) enrolled patients are on INTERIM, with a probability of maintaining intermittent administration of 59% (95% CI: 46-69). No patient lost the CCgR and only 9 additional patients lost the MMR while on intermittent treatment. All these patients resumed continuous imatinib treatment and regained the MMR. Thus, at ≥ 5 years, the probability of maintaing CCgR is 80% (95% CI 68-87) and the probability of maintaining the MMR is 61% (95% CI: 48-71). From start of INTERIM, 6 patients died but no deaths were related to CML progression (3 cases of other non haematological neoplasms, 1 stroke, 1 myocardial infarction, 1 chronic obstructive pulmonary disease).The PFS at ≥ 5 years is 94% (95% CI: 89-100) CONCLUSIONS: In summary, with a follow up ≥ 5 years, intermittent imatinib administration (INTERIM) confirmed to be safe, to produce a reversible increase of residual molecular disease in about one third of patients, but not to affect the long-term outcome. Aknowledgments: This work was supported in part by EuropeanLeukemiaNet (contract LSHC-CT-2004-503216) through the European Treatment and Outcome Study (EUTOS), supported by Novartis Oncology Europe, and COFIN 2009 Disclosures Russo: Celgene: Research Funding; Gilead: Research Funding; Novartis: Consultancy. Martinelli:Novartis: Speakers Bureau; Bristol-Meyers and Squibb: Speakers Bureau; Pfizer: Speakers Bureau. Soverini:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria; Ariad: Consultancy, Speakers Bureau. Turri:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Castagnetti:Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria. Breccia:novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Abruzzese:Novartis: Consultancy. Tiribelli:Novartis: Consultancy, Honoraria; Bristol-Meyers and Squibb: Consultancy, Honoraria. Rosti:Consultant: Consultancy, Speakers Bureau; Bristol-Meiers Squibb: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.1794.1794
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 2
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    An Observational Multicenter Study to Assess the Cost of Illness and Quality of Life in Patients with Myelodysplastic Syndromes in Italy
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 1023-1023
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    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1023-1023
    Abstract: Abstract 1023 Background: The annual incidence rate of myelodysplastic syndromes (MDS) in the general population is estimated at around 3–5/100,000. Because of a lack of specific therapies, until recently small attention has been devoted to costs of treatment of MDS. A specific Diagnosis-Related Group is still missing. In the US the mean annual cost for MDS patients ranges from $19,811 to $51,066. Aims: To assess the annual cost of illness (COI) and quality of life (QoL) of patients with MDS in Italy. Methods: The Costo Sociale delle Sindromi Mielodisplastiche e Qualità della vita in Italia (CoSMIQ) is an observational, cross-sectional, retrospective, prevalence-based, multicenter study based on an International Prognostic Scoring System (IPSS)-stratified sample of patients with MDS ≥18 years of age seen in standard clinical practice at 7 hematologic institutions across Italy (3 in the North; 2 in the Center; and 2 in the South). Demographics, clinical history, health care and non-healthcare resource consumption, and patients' and caregivers' productivity losses were collected by physicians using clinical records and information provided by patients. COI (in Euro (€) 2010) was determined utilizing a societal perspective. QoL was assessed via EORTC QLQ-C30 and QOL-E v.2 questionnaires, the latter being a new specific tool for the assessment of health-related QoL in patients with MDS. Kendall's tau rank correlation, chi-squared test, multivariate analysis of variance (ANOVA; MANOVA) and multiple linear regressions were performed when appropriate. Results: In all, 225 of 234 patients who met the inclusion criteria were analyzed (IPSS low risk: 124 patients; intermediate-1 (Int-1) risk: 75 patients; Int-2 and high risk: 26 patients) (Table). The total COI reached €27,980.4 ± 28,322.2 (mean ± standard deviation) (Figure). Cost-drivers of COI were antianemics (lower-risk) and antineoplastics (higher-risk). The Italian National Health Service (INHS) funded the greatest share of COI (from 97.4% to 99.5%). In general, CoSMIQ patients perform worse than the general population in all EORTC QLQ-C30 domains; the total global health status (QL) domain reached 65.1 ± 22.2 (low risk: 64.2 ± 22.3; Int-1 risk: 67.4 ± 22.1; higher-risk: 62.5 ± 22.3). QL was negatively correlated with COI (p=0.049) and patients' age (p=0.089), and positively correlated with disease duration (p=0.203). Keeping the other predictors constant, RBC transfusion dependence predicts increased COI (p=0.006) and lower QL (p=0.009). Regarding the QOL-E questionnaire, the QOL-E MDS-specific domain (MDSS) was positively correlated with total COI (p=0.0002), and patients' age (p=0.348) and negatively correlated with disease duration (p=0.013). The total QOL MDSS was 27.5 ± 19.8 (low risk: 25.3 ± 19.4; Int-1 risk: 29.6 ± 19.3; higher-risk: 31.6 ± 22.2). The total treatment-outcome index domain (QOL TOI) was 49.4 ± 14.4 (low risk: 49.1 ± 14.7; Int-1 risk: 48.3 ± 14.7; higher-risk: 53.9 ± 11.7). QOL TOI was negatively correlated with total COI (p=0.379), and patients' age (p=0.0003) and positively correlated with disease duration (p=0.162). Differences by IPSS group were not statistically significant for COI (p=0.191) or for any domain of the EORTC QLQ-C30 or QOL-E questionnaires (p=0.124; p=0.467). Conclusion: MDS dramatically increases INHS budgets while negatively impacting patients' QoL. The results of the CoSMIQ study highlight the strong correlation between RBC transfusion dependence and both COI and QL. Disclosures: Lazzaro: Celgene Srl: Research Funding. Martelli:Celgene Srl: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.1023.1023
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 3
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    Hammersmith Score Is Able to Identify Chronic Myeloid Leukemia Patients with Poor Prognosis Before Treatment with Second-Generation TKIs.
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 3409-3409
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    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3409-3409
    Abstract: Abstract 3409 A score aiming at early identification of CML patients showing sensitivity to second generation TKIs was proposed by the Hammersmith group. The score was created by analizing 80 patients and was based on 3 prognostic factors: previous cytogenetic response to imatinib, Sokal risk and recurrent neutropenia during imatinib. Subsequently, the score was validated in a small series of 28 patients. Aim of our study was to confirm the validity of this score and to establish its strength on a large group of CML patients resistant to imatinib and treated with second generation TKIs. One hundred twenty-seven patients were collected from 6 different Italian hematologic centers. There were 66 males and 61 females, median age 54 years (range 25–80). Twenty-seven patients received interferon before imatinib. Thirty patients had primary resistance, whereas 97 patients received second-generation TKI after acquired resistance to imatinib. The application of Hammersmith score was possible in 118 patients with available data: 52 patients were identified as good risk, 27 patients as intermediate risk and 38 patients as poor risk. The 1-year cumulative incidence of complete cytogenetic response (CCR) was 73% in good risk patients, 40% in intermediate risk patients and 23% in poor risk patients (p=0.0001). Similarly, the cumulative incidence of major molecular response (MMR) was 52% in good risk, 28% in intermediate risk and 13% in poor risk category (p=0.001). In the evaluation of event-free survival (EFS), events were considered loss of hematologic or cytogenetic response, disease progression, death for any cause, toxicity: the estimated 2-year event-free survival (EFS) was 89% in good risk, 70% in intermediate risk and 55% in poor risk group (p=0.0001). Progression-free survival (PFS) was defined as survival without evidence of accelerated or blastic phase: the estimated 2-year PFS was 97% in good risk, 93% in intermediate risk and 87% in poor risk category (p=0.05). Kaplan Meier estimated 2-year overall survival (OS) was 100% in the good risk, 93% in the intermediate risk and 82% in the poor risk category (p=0.001). In conclusion, as suggested by Milojkovic et al, some prognostic factors before starting second generation TKIs might predict cytogenetic response and outcome. As far as we known, the so-called Hammersmith score was not yet validated in large series of patients: we demonstrated that this score was able to discriminate patients at high risk of failure and consequent progression before treatment with second generation TKIs. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.3409.3409
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 4
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    Retrospective Application of European LeukemiaNet Provisional Criteria for Second-Generation TKI Chronic Myeloid Leukemia
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 2270-2270
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    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2270-2270
    Abstract: Abstract 2270 An update of the European LeukemiaNet criteria for monitoring response of chronic myeloid leukemia patients was recently published and provisional criteria to evaluate patients during second generation TKI therapy after resistance to imatinib were proposed. In our study we retrospectively tested these criteria in a large series of CML patients resistant to imatinib further treated with second generation TKIs with the aim to analyze the outcome of suboptimal response and failure patients compared to those with optimal response and to validate the provisional criteria for monitoring response. One hundred twenty-seven CML patients resistant to imatinib were collected from 6 different Italian hematologic centers. There were 66 males and 61 females, median age 54 years (range 25–80). Twenty-seven patients were in late chronic phase after IFN resistance. Ninety-seven patients received second-generation TKI after acquired resistance, whereas 30 patients had primary resistance. We found that at different time points (3, 6 and 12 months), patients classified as failure showed significantly worse 2-year overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) than sub-optimal and optimal response patients. At 3 months, “failure” patients, had an OS of 83% compared to 86% of sub-optimal and 97% of optimal response patients (p=0.001); PFS was 77% for failure patients compared to 92% and 99% for sub-optimal and optimal response patients, respectively (p=0.001), whereas EFS was 41% for failure vs 59% for sub-optimal (p=0.001) and 85% and optimal response patients, respectively (sub-optimal vs optimal p 〈 0.001). At 6 months, OS was 82%, 88% and 99% for failure, sub-optimal and optimal response patients (p=0.05), respectively; PFS was 82% for failure compared to 94% and 99% for sub-optimal and optimal response patients, respectively (p=0.001); EFS was 47% vs 69% for failure and sub-optimal response (p=0.001) and 86% for optimal response patients (sub-optimal vs optimal, p 〈 0.001). At 12 months again OS was 84% for failure patients compared to 95% and 99% for sub-optimal and optimal response patients (p=0.04); PFS was 86%, 95% and 99% for failure, sub-optimal and optimal response patients, respectively (p=0.001) and EFS was 48% for failure, 67% for sub-optimal response patients (p=0.002) and 89% for optimal response patients (sub-optimal vs optimal, p 〈 0.001). We found that ELN provisional criteria identified at any times worse EFS for sub-optimal response patients, similar to that of failure patients, and failure criteria at 3 months identified patients who had worse PFS and EFS. ELN provisional criteria for second-generation TKIs treated patients appear to clearly predict outcome and can be useful to identify patients at high risk of progression. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.2270.2270
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 5
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    Evaluation of Residual CD34+/Ph+ Stem Cells In Chronic Myeloid Leukemia Patients In Complete Cytogenetic Response during First Line Nilotinib Therapy.
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 3413-3413
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    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3413-3413
    Abstract: Abstract 3413 Introduction Imatinib mesylate is highly effective in inducing rapid hematologic and cytogenetic responses in the vast majority of chronic myeloid leukemia (CML) patients. Yet, discontinuation of treatment is associated with disease relapse probably due to the persistence of resistant leukemic stem cells representing a reservoir of the disease. On this regard it has been reported that BCR-ABL positive progenitor cells can still be detected in patients in complete cytogenetic response (CCyR) after short term of imatinib treatment (Bhatia R, et al. Blood. 2003;101:4701-4707) but also after a stable long lasting CCyR (Bocchia M, et al. Leukemia. 2008;22:426-428). Compared to imatinib, the second generation Tyrosin Kinase Inhibitor (TKI) nilotinib appears to eradicate more rapidly the bulk of CML cells, inducing high rate of CCyR and major molecular response (MMolR) after a very short period of treatment (78% CCyR and 52% MMolR at 3 months) (Rosti G, et al. Blood. 2009;114(24):4933-8). Despite nilotinib is a more potent TKI, it didn't appear to be more effective in eliminating in vitro CML progenitors than imatinib (Konig H, et al Leukemia. 2008;22:748-755). Up to date no data evaluating the persistence of Ph+ stem cells in early chronic phase CML patients during first line treatment with nilotinib have been reported. Patients, materials and methods We investigated the presence of residual CD34+/Ph+ cells in 24 CML patients in CCyR during first line nilotinib treatment. Patients were enrolled in 2 clinical trials (GIMEMA CML0307 and CAMN107A2303) and evaluation of residual leukemic stem cells was performed during a routine bone marrow aspirate after receiving specific patients informed consent. Bone marrow purified CD34+ cells were evaluated for BCR-ABL fusion gene by fluorescent in situ hybridization (FISH) analysis. A minimum of 100 interphase nuclei of purified CD34+ cells was considered optimal for FISH analysis. Results All 24 patients have been treated exclusively with nilotinib since diagnosis (17/24 at 400mg bid; 5/24 at 300mg bid; 2/24 at 400mg/day). At the time of analysis all 24 patients were in CCyR for a median time of 27 months (range 6–29) after being treated for a median time of 30 months (range 9–30) with this second generation TKI. Regarding molecular response 20/24 (83%) were in MMolR while only 1/24 (4%) was in CMolR. Harvest, purification and subsequent FISH analysis of bone marrow CD34+ cells was optimal in 15/24 (63%) patients, suboptimal in 5/24 (21%) patients (less than 100 interphase nuclei analyzed) and not adequate in 4/24 (16%) patients (less than 50 interphase nuclei). With respect to leukemic stem cells, residual CD34+/Ph+ cells were found only in 1/20 (5%) evaluable patients. Of note, in this patient 140 CD34+ interphase nuclei were analyzed and only 1 was found bcr-abl positive (0.7%). Conclusion Our study shows for the first time that in patients in CCyR during front line Nilotinib treatment residual CD34+/Ph+ stem cells are very rarely detected. These results quite differ from what was previously found in imatinib treated patients (Bocchia M, et al. Leukemia. 2008;22:426-428). In fact in the present series, only 1/20 (5%) patients treated with nilotinib in CCyR for a median time of 27 months showed residual CD34+/Ph+ cells, while in our prior study residual leukemic CD34+ cells were still detectable in 14/31 (45%) imatinib treated patients in stable CCyR (median of 39 months). Despite the limited number of patients studied, this novel evidence may support the better short term clinical results observed with nilotinib as first line treatment in CML. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.3413.3413
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
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    Health-Related Quality Of Life In Transfusion-Dependent Patients With Myelodysplastic Syndromes Treated With Deferasirox. A Multicenter Prospective Study
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2980-2980
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    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2980-2980
    Abstract: Anemia is a common symptom in patients with Myelodysplastic Syndromes (MDS) and although erythropoietic agents are often active, it is frequently treated with red blood cell (RBC) transfusions. A substantial proportion of patients might also eventually become transfusion-dependent and, Iron-chelating therapies might be important to minimize complications of iron overload. Objectives To investigate the impact of deferasirox therapy on health-related quality of life (HRQOL) of lower risk transfusion-dependent MDS patients over a one year period. Secondary objectives were to investigate relationships between HRQOL and ferritin levels and to explore the prognostic value of baseline HRQOL on the probability of achieving transfusion independence. Patients and Methods This was a prospective study whose clinical findings (i.e., primary endpoint was safety and tolerability) were previously reported. HRQOL was a secondary endpoint of the study and we herein report, for the first time, HRQOL prospective findings. Eligible patients included: MDS patients 18 years or older, International Prognostic Scoring System (IPSS) low or intermediate-1 risk and diagnosed with transfusional siderosis following a minimum of 20 blood transfusions. Patients received daily oral deferasirox at a dose between 10 and 30 mg/kg of body weight for a period of 1 year. HRQOL was assessed with the EORTC QLQ-C30. HRQOL at baseline and at 3, 6, 9 and 12 months after treatment start. The EORTC QLQ-C30 consists of 30 items and includes five functional scales (physical, role, emotional, social, and cognitive), three symptom (fatigue, nausea and vomiting and pain) and a global health status/QOL scale and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). The mean trend of HRQOL over time was estimated via a linear mixed model with a one-step autoregressive covariance structure. Such covariance structure provided the best model fit among those investigated. Results Overall, 159 patients were screened at 37 centers. The median duration of disease at enrollment was 32 months and median number of units of packed RBC received was 37. Seven patients did not start treatment at all and thus there were 152 expected HRQOL forms at baseline assessment. Out of these, 146 patients returned the questionnaire yielding a baseline compliance of 96%. No statistically significant differences over time were found for any scale of the EORTC QLQ-C30. Figure 1 depicts mean scores over time for selected scales of: fatigue, physical functioning, pain and global HRQOL. No HRQOL differences were found between patients with serum ferritin levels lower or higher than 2000 μg/L (pretreatment median value) at baseline. Also, the possible impact of ferritin level on HRQoL over time was estimated via a linear mixed model with a one-step autoregressive covariance structure. Coefficients and p values are reported in table 1. The prognostic impact of baseline HRQOL on the probability of achieving transfusion independence (i.e., defined as freedom from transfusion for 3 consecutive months) was investigated. Higher severity of pain (P=0.007) was associated with a greater likelihood of achieving transfusion independence. Multivariate analysis, controlling for age, IPSS risk score, time from diagnosis, number of previous blood transfusions and baseline ferritin level confirmed the independent value of pain (P=0.003). Conclusion Current findings suggest that Deferasirox therapy does not decrease HRQOL in lower risk transfusion-dependent MDS patients. Patients with higher baseline pain severity seems more likely to achieve transfusion independence and further analysis is needed to understand underlying reasons. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.2980.2980
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
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    5-Azacytidine, Valproic Acid and ALL-Trans Retinoic Acid in INT-2/High Risk Myelodysplastic Syndromes: Results of the GIMEMA MDS0205 Multicenter Trial
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 3648-3648
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    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3648-3648
    Abstract: Epigenetic changes have been shown to play a role and to cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). The potential reversibility of DNA and chromatin modifications makes chromatin remodeling enzymes attractive targets for therapeutic intervention in this disease. We conducted a phase II study on the combination of the DNMT inhibitor 5-azacitidine (5-AZA), the histone deacetylase inhibitor valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with intermediate-2/high-risk myelodysplastic syndromes. Bone marrow morphology was centrally reviewed before enrolment. VPA was given at 600–1500 mg daily to reach a final plasma concentration above 50 microg/ml, then 5-AZA was added at a standard dose of 75 mg/sqm daily, subcutaneously, 7 days for 8 cycles. In case of minor response, stable disease or failure after 4 cycles, ATRA was added at 30 mg/sqm orally daily, on days 8–27 for 4 cycles. Treatment was continued in responding patients until response persisted. The protocol included 62 patients (43 males, 19 females, median age 67 years, range 53–83 yrs). Diagnosis was RAEB for 37 patients (60.7%), RAEB-t for 21 (32.8%), and CMML for 4 patients (6.5%). The IPSS was int-2 (1.5) for 46 patients and High (≥2) for 16 patients. A valproic acid concentration between 45 and 55 microg/ml was reached in a median of 7 days (range 4–28 days). Three patients died before start of treatment, while 58.7% of patients (95% C.I.: 51.3–67.1) were alive at 12 months. Out of 27 patients who completed 8 treatment cycles, 8 patients (29.6%) obtained complete and partial remission, 3 patients (11.1%) major hematological improvement while 10 patients (37.4%) showed a stable disease. Transformation into AML or progression occurred in 20 patients. RBC transfusion needs decreased significantly from a median of 3 units (range 0–16) before start of treatment to 0 (range 0–7) after 8 cycles. Neurological toxicity occurred in 6 patients. Our data show that the 5-AZA/VPA/ATRA combination is safe and feasible in poor prognosis MDS patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.3648.3648
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 8
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    Treatment with Erythropoietic Stimulating Agents in IPSS Lower Risk MDS: Outcome Comparison Between 5q- and Non 5q- MDS Cases
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 2799-2799
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    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2799-2799
    Abstract: Abstract 2799 Background. In IPSS lower-risk Myelodysplastic Syndromes (MDS), anemia is the main therapeutic challenge. Erythropoietin stimulating agents (ESAs) can frequently correct anemia, but not all patients respond, and median response duration to ESAs is around 2 years (Park, Blood 2008;111:574). Patients with deletion of chromosome 5q are usually considered refractory to ESAs. Endogenous serum erythropoietin levels have been demonstrated in only one study to be higher in patients carrying del5q than in patients with Lower-Risk MDS and different abnormalities in karyotypes. Aims. We wanted to further analyze differences in management, efficacy and tolerability of ESAs therapy between MDS with and without del5q. Patients and Methods. We studied 239 MDS patients affected by IPSS low and intermediate 1 risk disease. 82 patients carried deletion of 5q, 12/82 in association with other anomalies. MDS patients with del 5q were WHO diagnosed as 9 RA, 9 RCMD, 13 RAEB-1, 47 5q minus syndrome and 2 unclassifiable MDS and divided by IPSS risk: 49 low risk and 33 INT-1. Patients without del5q were diagnosed as follows: 59 RA, 24 RARS, 43 RCMD, 17 RAEB-1, 4 CMML and 10 unclassifiable MDS. When subdivide per IPSS risk: 90 low risk and 67 INT-1. 75% of patients with del5q were female against 37% of patients without del5q. Medical record of patient were collected and reviewed, statistical analysis were perform with SPSS software. IWG criteria for response to ESA treatment were applied. Results. Endogenous erythropoietin (EPO) level at diagnosis were significant higher in patients with del 5q (mean 599,6 mU/ml) than in others (mean 99,3 mU/ml)(p=0.002). There was no significant difference, in terms of endogenous EPO levels, either stratifying by WHO classification (p=0.996) or by IPSS score (INT-1 325.8 mU/ml, low 138.6 mU/ml, p=0.120), or blast % (p 〉 0.05). Serum creatinine levels were correlated with endogenous EPO levels (p=0.003 Spearman's rho −0.258). Serum Epo was also correlated to age (p=0.026 Spearman's rho −0.183). No correlation was seen between number of transfusions at diagnosis and serum EPO levels and between hemoglobin levels and serum EPO levels. 18 patients (22%) with deletion of 5 q responded to ESAs treatment versus 56,8% of responding patients without del 5q (p 〈 0.001). Erythroid response was shorter p 〈 0.05 in MDS with del5q. ESA response was inversely correlated with endogenous serum EPO levels (p=0.000). In all of our cohort rate of response to ESA was lower in patients with excess of blast than the others (32% vs 49% p=0,022). Conclusion. ESAs treatment has to be considered first line therapy for IPSS lower risk MDS patients with syntomatic anemia, also when carrying del5q. Endogenous EPO levels are constantly higher, throughout disease history, in del5q MDS cases. This could account for worse ESA response. Anemia and WHO classification do not seem to influence ESA response. Excess of blasts was an adverse prognostic factor to ESA response with or without del5q. A deeper insight into mechanisms of resistance to ESAs is needed. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.2799.2799
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 9
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    Low-Dose Dasatinib as Front-Line Therapy for Elderly (〉 60 Years) Patients with CML
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 2293-2293
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2293-2293
    Abstract: Abstract 2293 Background. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. A phase III dose optimization study showed that in patients with chronic phase (CP) chronic myeloid leukaemia (CML), dasatinib at 100 mg once daily improved the safety profile while maintaining efficacy compared with the previously recommended dose of 70 mg twice-daily. Few data exist on the efficacy and safety of dasatinib in elderly CML patients. Aims. The aim of the study was to evaluate the impact of dose reduction on dasatinib efficacy. Methods. We revised 129 unselected pts with CP CML aged 〉 60 yrs treated in 21 Italian haematological Institution, who received dasatinib after being resistant/intolerant to imatinib. Among this group 70 pts were given dasatinib at adjusted-dosage below the standard recommended dose of 100 mg daily for 〉 6 months. In relation to the dose modulation, patients were divide in 2 groups: group-a (21/70, 30%) received a starting dose of 20 mg daily dose excalated to the maximum tolerated dose of 70 mg daily; group-b (49/70=70%) received a starting dose of 100 mg daily, successively adhusted according to tolerance. Sokal score was evaluable for 59/70 patients (low for 16, intermediate for 28, high for 15). All patients were analyzed for haematological, cytogenetic and molecular response. Results. All patients were fully evaluable for response at a median FU time of 25 mos (range 0,7- 56,3 mos). Eight pts (11.4%) discontinued treatment due to intolerance. Response rates were 25,7% (18pts), 24.3% (17 pts), 15.7% (11 pts), 10% (7 pts), 12.8% (9 pts) for complete haematologic response (RHC), complete cytogenetic response (RCyC), major molecular response (RMolM), complete molecular response (RMolC), partial cytogenetic response (RCyP), respectively. Median Cumulative event free survival (EFS) and overall survival (OS) were 21.3 and 27.3 mos respectively. We did not observe any significative difference in term of response between group A and B receiving different doses. Interestingly, 3/9 patients in group A who had a transient loss of molecular response achieved major molecular response after dose escalation to 50 mg. Conclusions: Dasatinib given at a lower dose than currently recommended is still effective in elderly CML patients. However, more close molecular monitoring is advised when lower doses are prescribed. Studies in larger series are warranted to better define optimal dose and schedule of dasatinib in this frail patient population. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.2293.2293
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
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  • 10
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    Lenalidomide in Myelodysplastic Syndromes with 5q Deletion. Results From the Italian National Cancer Registry
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 3850-3850
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3850-3850
    Abstract: Abstract 3850 Background: Lenalidomide (LEN) is available in Italy for patients with intermediate-1- and low-risk myelodysplastic syndromes (MDS) associated with 5q deletion (5q-) since October 2008, based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96). LEN is an oncological drug subject to intensive monitoring and, when it is prescribed in MDS, physicians are requested to enter the patient into a registry, which is entirely web-based. Methods: This observational, retrospective, multicenter study (registered at www.clinicaltrials.govasNCT01347944) has enrolled patients at 40 centres of 43 authorized in Italy. The study was approved by the ethic committee of each participating institution. The purpose was to analyse data available in the Registry and to integrate them with additional clinical and laboratory findings by filling up new e-forms in all cases with MDS and 5q- receiving LEN from October 31st, 2008 until the present. Diagnosis, treatment, follow-up and re-evaluation of patients were considered. Results: Study population included patients pre-treated and not pre-treated, with or without the integration form at the end of treatment. Pre-treated were defined as patients who were given LEN (from 1 to 12 cycles, median 3) before entering the AIFA registry. 158 patients (42 pre-treated and 116 not pre-treated) were eligible for this preliminary analysis. Median age was 75 (range, 38–89 years); 6 patients were younger than 50. There were 108 females (68.35%) and 50 males (31.6%) (table). Hematological findings evaluated at diagnosis were: hemoglobin ( 〈 8.5g/dL, 43% and 〉 8.5g/dL, 57%), macrocytosis (MCV 〉 98 fL, 54.4%), platelet count ( 〈 140×109/L, 24.7%; between 140 and 400×109/L, 56.3%; 〉 400×109/L, 19%). Median white blood cell count was 4× 103/L with 54% neutrophils. Bone marrow blasts ≤5% were found in 75.9% of cases. The 5q- was detected by conventional cytogenetics in 131/158 cases (82.9%): it was isolated in 110 cases, associated with one additional in 15, and in complex karyotypes in 6. In 2 cases with normal karyotype and in 25 cases with failed cytogenetics the 5q- was demonstrated by fluorescence in situ hybridization (FISH). These cases could not be grouped as isolated or non-isolated. Patients received LEN at a daily dose of 10mg or 5 mg for 21 of 28 days as the starting dose. The dose and schedule was adjusted mainly based on blood count and hematological toxicity. Median time on treatment was 15.5 months (range, 1–45). Major and minor criteria for hematological and cytogenetic response are under evaluation. Transfusion independence at 6 months was reached in 77/103 cases (74.75%). Hematological toxicity could be evaluated in 148 cases. A total of 555 neutropenia events (36% grade 3 and 12.9% grade 4) and 422 thrombocytopenia events (10.9% grade 3 and 6.16% grade 4) were seen. Among 69 evaluable cases, 11 (15.9%) developed acute myeloid leukemia. In this group the median age was 72 (range, 62–85) and there were 4 males and 7 females. The median number of LEN cycles was 6 (range, 2–31). The median time from diagnosis of MDS was 34 months (range, 4–68). Chromosome 5q- at diagnosis was demonstrated by conventional cytogenetics in 8 cases (6 isolated and 2 with one additional change) and by FISH in 3. Comments: The Italian Drug Agency (AIFA) Registry provided us with a large series of MDS cases with 5q- to investigate appropriatness of LEN prescription and management. As expected LEN was successful to obtain transfusion independence in this patient population. Hematological toxicity was manageable. The number of cases with leukemic evolution is in line with data reported in the literature. These cases will be further investigated. Disclosures: Mecucci: CELGENE: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.3850.3850
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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