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  • 1
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    Age Influences Initial Dose and Compliance to Imatinib In Chronic Myeloid Leukemia Elederly Patients but Concomitant Comorbidities Appear to Influence Overall and Event-Free Survival
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 2751-2751
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2751-2751
    Abstract: Abstract 2751 Comorbidities have been identified as significant determinants of response to therapy in elderly patients with acute myeloid leukemia, breast cancer, head and neck, and lung cancer. Charlson comorbidity index (CCI) is a list of comorbidities with a weight assigned from 1 to 6 derived from relative risk estimates of a proportional hazard regression model using clinical data. We applied CCI stratification on a large cohort of chronic myeloid leukemia (CML) very elderly patients ( 〉 75 years) treated with imatinib, in order to observe the impact of concomitant diseases on both compliance and outcome. One hundred and eighty-one patients were recruited by 21 Italian centers. There were 95 males and 86 females, median age 78.6 years (range 75–93.6). According to Sokal score, 106 patients were classified as intermediate risk and 55 as high risk (not determined in 20 patients). According to CCI stratification, 71 patients were score 0, 50 patients had a score 1, 37 patients had score 2 and 23 patients had score ≥ 3. Imatinib standard dose was reduced in 68 patients independently from the evaluation of baseline comorbidities but based only on physician judgement: 43.6% of patients with score 0 started with a reduced dose (200–300 mg/day) compared to more than 50% of patients with score ≥ 3. No significant differences were found in terms of further reduction of the dose (39% in patients with score 0 compared to 21% in patients with score ≥ 3) or in terms of discontinuation due to toxicity (58% in patients with score 0 vs 48% in patients with score ≥ 3). We did not find significant differences as regards the occurrence of hematologic side effects, probably due to the initial reduction of the dose: 39% of patients with score 0 experienced grade 3/4 hematologic toxicity (most commonly anemia) compared to 35% of patients with score ≥ 3. Independently from the initial dose, comorbidities again did not have an impact on development of grade 3/4 non-hematologic side effects (most common skin rash, muscle cramps and fluid retention): 62% of patients with score 0 compared to 35% of patients with score ≥ 3. Notwithstanding the reduced dose and the weight of comorbidities we did not find differences in terms of efficacy: 66% of patients with score 0 achieved a CCyR compared to 56.5% of patients with score ≥ 3. Comorbidities appeared to have an impact on EFS (34 months for patients with score 0 vs 23.5 months for patients with score ≥ 3) and influenced the median OS (40.8 months for patients with score 0 vs 10.6 months for patients with score ≥ 3). Our results suggested that treatment of very elderly CML patients might be influenced by personal physician perception: evaluation at baseline of comorbidities according to CCI should improve initial decision-making in this subset of patients. Disclosures: Russo Rossi: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Alimena:Novartis: Honoraria; Bristol Myers Squibb: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.2751.2751
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
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    Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome
    Impact Journals, LLC ; 2016
    In:  Oncotarget Vol. 7, No. 48 ( 2016-11-29), p. 80083-80090
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 7, No. 48 ( 2016-11-29), p. 80083-80090
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v7i48
    DOI: 10.18632/oncotarget.11657
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2016
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  • 3
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    Moderate/ Severe Pleural Effusion As a Side Effect in Very Old Chronic Myeloid Leukemia (CML) Patients Undergoing Imatinib Treatment
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 4445-4445
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4445-4445
    Abstract: Abstract 4445 Imatinib advent has provided for old CML patients too a chance for an effective treatment, aimed at complete cytogenetic and major molecular response. Indeed, a few studies reported in patients more than 65 year old a response rate comparable to that observed in younger ones. However, fluid retention, a common side effect of imatinib therapy, seems to occur more frequently in elderly patients. Indeed, periorbital and ankle oedema are common patients’ complaints, whereas pleural effusions have not been usually observed in imatinib-treated patients. Conversely, pleural effusions (usually mild to moderate) occur in about 14% of patients treated with the second generation tyrosine-kynase inhibitor (TKI) dasatinib at the optimal dosage of 100 mg by single daily administration. We conducted a retrospective survey of 181 Italian CML patients, above the age of 75, treated with imatinib for chronic phase CML. Among sixty-five patients who were more than 80 year old we observed 5 cases (7.7%) who displayed a severe (grade 3: 4 patients) or moderate (grade 2: 1 patient) pleural effusion. Conversely, such a side effect was not observed in any of the 101 slightly younger (75–80 year old) patients. The 5 patients displaying a pleural effusion were all males, 80.3 – 88.7 year old at the time of imatinib start. One patient was in late chronic phase, and had received hydroxyurea for more than 2 years before imatinib start, whereas the other 4 started imatinib therapy within 2 months from diagnosis. All 5 patients had at least one cardiovascular co-morbidity. Pleural effusion developed after 3–8 months of imatinib therapy. Pericardial effusion and peripheral oedema were also evident in two and one of the 5 patients, respectively. Imatinib was definitely discontinued in 2 patients (one of them had cytogenetically resistant disease) whereas the drug could be resumed, after a few months of interruption, in the other 3, in one case after intolerance to second generation TKI nilotinib. Three patients died: two of myocardial infarction and one for CML blastic phase at 45, 31 and 54 months, respectively, from diagnosis. Two patients are alive, one in major cytogenetic response with resumed imatinib treatment, at 12 and 30 months from diagnosis. Our survey evidenced a significant percentage of very old patients who developed a pleural effusion during imatinib treatment. Although our casistic of patients with pleural effusion is small, some differences are evident, compared to the more common dasatinib-induced pleural effusions. In the case of dasatinib, most of pleural effusions are mild, unrelated to peripheral oedema, and may have an immune-related aetiology. In our imatinib-treated patients pleural effusions were more severe and frequently accompanied by pericardial involvement. Moreover, they were restricted to very old patients and possibly correlated to cardio-vascular co-morbidities. In conclusion, although imatinib still represents the best CML treatment for most of very old patients too, these should be strictly monitored for fluid retention and possible appearance of a pleural and or pericardial effusion. Disclosures: Russo Rossi: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.4445.4445
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 4
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    Age influences initial dose and compliance to imatinib in chronic myeloid leukemia elderly patients but concomitant comorbidities appear to influence overall and event-free survival
    Elsevier BV ; 2014
    In:  Leukemia Research Vol. 38, No. 10 ( 2014-10), p. 1173-1176
    Details
    In: Leukemia Research, Elsevier BV, Vol. 38, No. 10 ( 2014-10), p. 1173-1176
    Type of Medium: Online Resource
    ISSN: 0145-2126
    URL: Article
    DOI: 10.1016/j.leukres.2014.06.020
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 2008028-1
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  • 5
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    Chronic Myeloid Leukemia with Deletions on Der(9) Shows Mir-199b Downregulated Expression.
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 1083-1083
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1083-1083
    Abstract: MicroRNAs (miRNAs) are small, single stranded non-coding RNAs, 19–24 nucleotides long, involved in crucial biological processes, including differentiation, apoptosis and proliferation. Recent evidence indicates that miRNAs may play an important role in tumorigenesis; changes in miRNAs expression level were identified in many types of human hematological and solid malignancies. To date, several papers have reported the occurrence of genomic deletions flanking the breakpoint on der(9)t(9;22) in 10%–18% of patients with chronic myeloid leukemia (CML). The most probable consequence of der(9) deletions is the loss of tumour suppressor genes, conferring a proliferative advantage to the Philadelphia-positive clone. On the other hand, two miRNAs, namely miR219-2 and miR-199b, are found to map centromeric to the ABL gene within the chromosomal region at 9q34 that is frequently lost in CML patients with der(9) deletions. In this study, we investigated the loss of miR-219-2 and miR-199b by fluorescence in situ hybridization (FISH) analysis with specific bacterial artificial chromosome (BAC) probes in 68 CML cases bearing der(9) deletions. We further evaluated miR-219-2 and miR- 199b expression levels by quantitative real-time polymerase chain reaction (qRT-PCR) experiments in cases showing deletions of at least one of these miRNAs. Depending on RNA sample availability, miRNAs expression level was evaluated in 7 and in 5 CML cases with miR-219-2 and miR-199b deletions, respectively. Statistical analysis of the relative expression results was performed by the Relative Expression Software Tool (REST). To explore the predicted miR-199b target genes, the miRGen targets database (http:// www.diana.pcbi.upenn.edu/cgi-bin/miRGen/v3/Targets.cgi) was queried; this interface provides integrated data of four widely used target prediction programs (miRanda, PicTar, TargetScan, DIANA-microT). FISH experiments revealed the loss of miR-219-2 and miR-199b in 17 (25%) and 10 (15%) out of 68 patients. The miR-199b expression study showed a downregulation in the analyzed group of 5 CML cases with miR-199b deletion as compared to a pool of 10 patients without deletions. The expression level of the miR-199b was 0.279 and the difference between the two groups was statistically significant (p= 0.028). On the contrary, the miR- 219-2 analysis did not reveal a detectable expression level in the examined patients. There were 26 predicted miR-199b target genes, involved in several biological processes such as signal transduction (Protein phosphatase inhibitor 2, PPP1R2), regulation of transcription (Hepatic leukaemia factor, HLF), chromosome organization and biogenesis (Zinc finger protein 238, ZNF238), cell proliferation (Mitogen-activated protein kinase 11, MAP3K11) and DNA repair (UV excision repair protein RAD23 homologue B, RAD23B). Among the CML patients evaluable for the response to the treatment, all cases with the miR-199b deletion were resistant to IFN-a and imatinib therapy. In conclusion, our data demonstrate a crucial role for miR-199b in CML cases bearing der(9) deletions. This miR-199b downregulation could influence the expression level of different target genes modifying important cellular pathways. Further analysis of miR-199b target genes will be needed to shed light on the link between miRNAs and CML.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.1083.1083
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 6
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    Chronic Myeloid Leukemia with Variant t(9;22) Shows Dysregulated Expression of Genes Included in Pivotal Cellular Pathways
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1674-1674
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    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1674-1674
    Abstract: Abstract 1674 The t(9;22)(q34;q11) generating the Philadelphia chromosome and the BCR/ABL1 fusion gene represents the cytogenetic hallmark of chronic myeloid leukemia (CML). About 5–10% of CML cases show variant translocations with the involvement of other chromosomes in addition to chromosomes 9 and 22. The greater frequency of occurrence of genomic microdeletions proximally to ABL1 or distally to BCR has been reported in CML cases with variant translocations (30–40%) than in cases with a classic t(9;22) (10–18%). The prognostic significance of variant t(9;22) was unclear and debated in the pre-imatinib era, whereas recent studies of large CML series showed that the presence of variant translocations has no impact on the cytogenetic and molecular response or on prognosis (Marzocchi et al. Blood 2011,117:6793-800). However, the molecular bases of differences between CML patients with classic and variant t(9;22) have never been elucidated. Here we report a gene expression profile analysis of 8 CML cases with variant t(9;22) and 12 patients with a classic t(9;22). RNA samples were extracted from bone marrow cells and hybridized on the Agilent SurePrint G3 Human GE 8×60K Microarray slide (Agilent Technologies). Ingenuity Pathways Analysis (IPA, www.ingenuity.com) software was used to provide an accurate biological and statistical analysis of microarray experimental data revealing functional relationships among the identified genes. Gene expression analysis identified a 59 gene set able to distinguish the two CML subsets. These genes are mostly involved in the development of the hematological system and in the occurrence of hematological diseases. Forty-five out of 59 (76%) genes were up-regulated, causing the probable activation of different molecular mechanisms such as cellular responses to stimuli, protein degradation, DNA repair, cell cycle progression. IPA analysis revealed that most of the dysregulated genes are included in a network where they are functionally linked to MAPK p38, AKT, and NFKB. Moreover, several genes play a role in cytoskeleton organization (WIPF1), in signal transduction and cell cycle progression (TRIB1, PDE4B, PTK2B, PLK3), in regulation of apoptosis (ZFAND5, STK17B), and in protein degradation (ZFAND5, SNRPG). On the contrary, among the downregulated genes, 5 (BCDIN3D, TMEM68, HILPDA, TMEM68, and C17orf61) establish direct interactions with ubiquitin C (UBC), a crucial gene involved in different intracellular mechanisms such as protein degradation, DNA repair, cell cycle regulation, and the regulation of other signaling pathways. In conclusion, gene expression profiling in cases with variant t(9;22) revealed biological differences in this CML subset. Our data show an overall deregulation of genes involved in hematological system development and in cell proliferation signaling pathway. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.1674.1674
    RVK:
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 7
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    Unfavourable Outcome and Heterogeneity of Partner Chromosomes in Chronic Lymphocytic Leukemia with 14q32/IGH Translocations.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4686-4686
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4686-4686
    Abstract: Translocations of 14q32/IgH have a low incidence in CLL. Partner chromosomes and the prognostic significance are poorly defined. Four hundred thirty cases of CLL seen at the Hospitals of Ferrara, Salamanca and Siena between 1992 and 2006 were studied. Inclusion criteria were: diagnosis of CD5/CD19+ CLL with k/λ restriction, cytogenetic/FISH data, immunophenotypic data, complete hematological and clinical data. Lymphomas in leukemic phase were excluded. FISH was performed for 17p13/TP53, 11q22.3/ATM, 6q21, chr 12 centromere, 13q14 and 14q32/IGH. Patients with no detectable aberration or isolated 13q− were included into a favourable cytogenetic group (group 1), those with +12, 6q− or 1–2 aberrations into an intermediate risk group (group 2) and those with 17p−, 11q−, ≥ 3 aberrations into an unfavourable group (group 3). Cases with 14q32/IGH translocation as primary chromosome change represented a specific category (group 4) and were studied with FISH probes for the detection of partners (BCL1, BCL2, BCL3, BCL6, c-MYC, BCL11A, PAX5, CCND3, CDK6). One hundred eighty-six cases were allocated into group 1; 158 into group 2; 64 into group 3, and 22 into group 4. Additional aberrations were found in a minority of cells in 8 patients in group 4. Being the aim of the study to assess whether the 14q32/IGH translocation represented an unfavourable parameter as compared with cases in the favourable or intermediate cytogenetic risk groups, cases within group 3 were excluded from the analysis and the data presented here will refer to 366 patients belonging to groups 1,2 and 4. Translocation partners of 14q32/IGH were identified in 9/22 cases: 2p13/BCL11A, (n 1); 6p21/CCND3 (n 1); 7q21/CDK6 (n 1); 18q21/BCL2 (n 6). Thirteen cases did not show involvement of the loci studied. Cases with 14q32/IGH translocations were characterized by typical morphology and classical immunophenotype (score 4–5 in 92% of the cases). Unmutated IGVH genes were found in 11/18 cases tested (61%); ZAP-70 was positive in 3/5 cases tested. Median age was 63.5 years (range 18–97), male:female ratio 240/126; 345 patients were in Rai stage 0-II, 21 were in stage 3–4; CD38 was positive in 137/366 cases. There was no difference between groups 1,2 and 4 for age, stage, male:female ratio, hematological parameters at diagnosis, IGVH mutations and ZAP70. CD38 was more positive in group 4 than in group 1 (p=0.028). There was no difference in survival and treatment free interval (TFI) when comparing cases in group 4 with and without additional aberrations. Cases in group 4 had a shorter TFI and a shorter survival when compared with group 1 (p=0.02) and group 2 (p=0.02). The difference maintained its statistical significance at multivariate analysis for TFI (p=0.02) along with stage (p 〈 0.0001) and CD38 positivity (p 〈 0.0001) and for survival (p=0.02) along with sex (p=0.006) and stage (p=0.0001). In conclusion, the 14q32/IGH translocation in CLL shows heterogeneity of partner chromosomes and it represents a cytogenetic marker predicting for an evolutive form of CLL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4686.4686
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 8
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    Imatinib In Very Elderly CML Patients: What Can We Achieve?.
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 1229-1229
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1229-1229
    Abstract: Abstract 1229 In the “real world” of clinical practice, many very elderly CML patients have been treated with imatinib (IM), but there are few data on the results and the best initial dosage in such patients. To highlight peculiar aspects of toxicity and efficacy of IM in this subset which accounts for at least 10–15% of all CML cases, we retrospectively revised 156 CML patients in chronic phase treated with IM when aged 〉 75 years from 23 haematological Institutions in Italy; there were 85 males and 71 females, median age at IM start was 78.4 years (IR 76.1 – 81.4), Sokal Risk at diagnosis was low in 2 patients, intermediate in 90, high in 50 and not evaluable in 14. One or more concomitant diseases requiring specific treatments were present in 144/156 patients (92.3%), with 94 patients (60.2%) assuming 3 or more concomitant drugs. Thirty patients (19.2%) were in late chronic phase (≥ 12 months from diagnosis) and pretreated (25 with HU and 5 with IFN) before starting IM; on the whole, median time from diagnosis to IM was 1.2 months (IR 0.5 – 3.6). Starting dose of IM was 400 mg/day in 117 patients (75.0%) and 300 mg/day or less in 39 patients (25.0%); overall, 59 patients (37.8%) (52/117 at 400 mg starting dose and 7/39 at 3 300 mg starting dose) needed a dose reduction and 18 (11.5%) discontinued IM for toxicity (early toxicity in 13 and late toxicity in 5). Excluding the 13 patients who discontinued IM due to early toxicity, maximum tolerated daily dose during treatment was 400 mg in 63 patients, 300 mg in 51 patients and 〈 300 mg in 29 patients. According to CTC-AE, grade 3 – 4 hematological and extra-hematological toxicities were observed in 34 (21.7%) and 34 (21.7%) patients, respectively; 5 patients (3.2%) presented a pleural effusion during IM treatment. After a median treatment period of 29.4 months (IR 7.9 – 54.4), 8 patients (5.1%) are still too early ( 〈 6 months of treatment), 13 (8.3%) discontinued IM due to early toxicity, 3 (1.9%) were resistant and 1 (0.7%) died from unrelated cause early after IM initiation: the remaining 131 patients (84.6%) achieved a complete haematological response (CHR). Among these 131 patients in CHR, 11 refused any other karyotipic or molecular evaluation (1 lost CHR and shifted to hydroxyurea, 4 are still alive in CHR, 6 died in CHR from unrelated causes), 17 achieved CHR only and 103 (66.0% of all 156 patients) achieved a cytogenetic response (CyR), which was major in 11 patients and complete (CCyR) in 92 (58.9% of all 156 patients). In addition, among the 92 patients in CCyR, 62 (39.7% of all 156 patients) achieved a molecular response (major molecular response in 40 patients and complete molecular response with an undetectable BCR/ABL hybrid gene at qualitative nested PCR in 22 patients). After a median follow-up of 34.0 months (IR 12.9 – 60.0), 36 patients have died (5 from disease progression and 31 from unrelated causes), 4 patients were lost to follow-up and 116 are still alive: 2-year and 4-year overall survival were 90.2% (CI95% 84.8 – 95.6) and 76.8% (CI95% 68.6 – 85.0), respectively. In conclusion, results from this large unselected cohort of patients show that should be definitely considered unethical to avoid IM therapy to any elderly patient; no upper age limit should be given but also very elderly (and with concomitant severe diseases) patients should have this chance of cure. The role of a reduced starting dose of IM warrants further studies. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.1229.1229
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 10
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    Gene expression profiling of chronic myeloid leukemia with variant t(9;22) reveals a different signature from cases with classic translocation
    Springer Science and Business Media LLC ; 2013
    In:  Molecular Cancer Vol. 12, No. 1 ( 2013), p. 36-
    Details
    In: Molecular Cancer, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2013), p. 36-
    Type of Medium: Online Resource
    ISSN: 1476-4598
    URL: Article
    DOI: 10.1186/1476-4598-12-36
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2091373-4
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