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  • American Society of Hematology  (104)
  • 1
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    Differences in Clinical Course and Management of Sars-CoV2 Infection in Patients with Chronic Lymphocytic Leukemia between the Sequential Pandemic Phases: An Eric Study
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2333-2337
    Details
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2333-2337
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2022-163259
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Amplification of the ABL Gene in T-Cell Acute Lymphoblastic Leukemia (T-ALL).
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1083-1083
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1083-1083
    Abstract: In acute leukemias gene amplification occurs with incidence of 1–10%. On conventional cytogenetic (CC) studies it is usually seen either intrachromosomally as homogeneously staining regions (HSRs) or extrachromosomally as double minute chromosomes (dmins). Fluorescence in Situ Hybridization (FISH) has established that the genes most frequently amplified in ALL are AML1 and MLL. Recently, the Leukaemia Research Fund UK Cancer Cytogenetic Group has detected the amplification of the ABL gene in 5/210 childhood and in 3/70 adult T-ALL and has suggested that this genetic abnormality might identify patients with a generally poor event-free survival (EFS). The present study was aimed at determining the incidence and clinical significance of ABL amplification in a series of 31 consecutive adult T-ALL patients. All of them had been submitted to routine FISH screening for BCR/ABL and TEL/AML1 fusions and for MLL amplification. ABL amplification was detected by chance in two patients (6.4%). In one CC did not yield analysable metaphases and in the other it showed the following karyotype: 46,XX/46,XX,t(1;3)(p34;p21),del(6)(q21),del(7)(q32). FISH with a painting probe specific for chromosome 9 detected an occult trisomy in the patient without analysable mitosis and a normal pattern in the other one. In both patients the number of ABL signals varied from cell to cell and the observer was always unable to count them properly. FISH on mitotic cells showed that ABL additional copies were localized neither on chromosome 9 nor on any other chromosome and revealed that amplification was extrachromosomal in nature even if no dmins were visualized. Therefore, it was hypothesized that the amplified ABL sequences might be localized on submicroscopic extrachromosomal structures, the episomes. In order to check whether the ABL gene was really over-expressed we performed a quantitative RT PCR (Q RT PCR) assay using the β-2-microglobulin as reference gene and total RNA from a normal subject for calibration. Quantification was made using the DDCt method. By this way we found that on clinical diagnosis the two patients expressed the ABL gene nine and twelve times more than the control. From a clinical point of view both patients were males. They had a high white blood cell count (31.8 and 21.8x109/L); their blast cells exhibited a T-ALL immunophenotype and a L2 morphology; their lactic dehydrogenase level was elevated. One patient achieved a complete remission (CR) of fifteen month duration and relapsed while still on maintenance treatment, the other did not respond to chemotherapy. In the former patient ABL expression was normal in CR but increased again on disease recurrence. In conclusion our data show that i) FISH is absolutely required to identify a new subset of T-ALL patients characterized by ABL amplification, ii) the role of ABL amplification in T-ALL pathogenesis is still obscure, iii) large cooperative studies are required to better define the clinical outcome of these patients whose EFS seems to be poor, iiii) Q RT PCR might be used to quantify minimal residual disease.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.1083.1083
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Randomized Trial of Busulfan with Cyclophosphamide Versus Busulfan with Fludarabine As Preparative Regimen to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: A Study from the Gruppo Italiano Trapianto Midollo Osseo (GITMO)
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 727-727
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 727-727
    Abstract: Background The combination of a myeloablative dose of intravenous (iv) busulfan with cyclophosphamide is the standard preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) patients. However, in patients older than 40 years, this conditioning can be associated to high non relapse mortality (NRM). A similar myeloablative dose of busulfan combined to fludarabine was found associated to a lower NRM in older AML (Alatrash, BBMT 2011). Patients and study design The Gruppo Italiano Trapianto Midollo Osseo (GITMO) conducted a Phase III, randomized, multicenter, trial to compare the standard myeloablative combination of iv busulfan (Busilvex®, Pierre Fabre, Boulogne, France) at a dose of 0.8 mg/kg/6h over two hours infusion for 4 consecutive days (16 doses), for a total dose of 12.8 mg/kg, in combination with cyclophosphamide at the dose of 60 mg/kg/day for 2 consecutive days for a total dose of 120 mg/kg (BUCY2 arm) or fludarabine at the dose of 40 mg/m2/day for 4 consecutive days, for a total dose of 160 mg/m2 (BUFLU arm). Eligible were patients with a diagnosis of AML in 1st or 2nd complete remission (CR) with an age ≥40 and ≤ 65 years, and the availability of an HLA compatible sibling or unrelated donor as defined by molecular high-resolution typing (4 digits) of the HLA gene loci class I (HLA- A, B, and C) and class II (DRB1). Excluded were patients with a t(15;17) or PML/RARα positive APL or with a t(8;21)(q22;q22) or an inv(16) or t(16;16)(p13;q22) positive AML in 1st CR. The GvHD prophylaxis was based on conventional Cyclosporine A and Methotrexate. In case of unrelated donors, anti Thymocyte Globulin (Thymoglobuline®, Sanofi-Aventis) was given at a total dose of 5 mg/kg (or 7.5 mg/kg, in case of HLA acceptable disparity) (one antigen/allele disparity in class I, or one allele disparity in class II). The primary study end-point was the one-year NRM using an intent-to-treat analysis. The required sample size was calculated assuming that the one-year NRM would have been halved (from 25% to 12.5%) in the BUFLU arm. The cumulative incidence of NRM was estimated by considering relapse as a competing event. All outcomes were evaluated from the date of transplantation. The study was approved by the Institutional Review Boards of each center. Results From July 2008 to February 2013, 25 centers in Italy and 1 in Israel, enrolled 245 patients who were randomly assigned to BUCY2 (n=121) or BUFLU (n=124), stratified according to donor type and remission (1st vs. 2nd or more). The main clinical features (balanced between the randomization arms) were as follows: the median age was 50 years, 209 patients (85%) were in 1st and 36 (15%) in 2ndCR and the ELN risk subgroups were good (11%), intermediate-1 (46%), intermediate-2 (20%) and adverse (23%). The donor was a sibling related (n= 112, 46%) or matched unrelated (n= 133, 54%) while the stem cell graft was the peripheral blood (PB, n= 168, 69%) or the bone marrow (BM, n= 77, 31%). The overall survival rate in the BUCY2 and BUFLU arm was 71% vs. 78% at 1 year, 65% vs. 62 % at 2 years and 56% vs. 57% at 5 years, respectively (P=ns). A non-significant lower incidence of relapse was documented in the BUCY2 vs. the BUFLU arm being 20.7% vs. 24.2% at 1 year, 25.6% vs. 29% at 2 years and 28.9 vs. 32.3 at 5 years, respectively. On the contrary, at 1 year, the overall NRM in the BUCY2 arm was 17.4% vs. 7.3% in the BUFLU (Gray Test P=0.02). At 2 years and throughout the study, the same significantly different NRM was observed between study arms being respectively 18.2% vs. 8.9% and 19% vs. 9.7% (Gray Test P=0.03) (Figure 1). Causes of NRM in the BUCY2/BUFLU arms were: infections 8/6, organ failures 9/0, GvHD 5/3, hemorrhage 1/1, others 0/2. All in all, at 1, 2 and 5 years the leukemia free survival of the BUCY2 and BUFLU arm was similar being 62% vs. 69%, 56% vs. 62% and 50% vs. 56%, respectively (P=ns) (Figure 2). The number of patients with grade III-IV acute GvHD was higher in the BUCY2 arm (P= 0.02). There were no significant between-group differences in the incidence of chronic GvHD. Conclusion In AML patients older than 40 years, the reduced toxicity conditioning with iv BUFLU significantly reduced the NRM compared to BUCY2. The increased incidence of leukemia relapse in the BUFLU arm was not associated with a detrimental effect on overall and leukemia free survival. (Funded by a grant from the Agenzia Italiana per il Farmaco (AIFA), ClinicalTrial.gov Identifier: NCT1191957). Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Rambaldi: Pierre Fabre Pharma: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.727.727
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 4
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    Long-Term Follow-up in Very Elderly Patients with Chronic Myeloid Leukemia Treated with Imatinib Frontline
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1598-1598
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1598-1598
    Abstract: In the current clinical practice, imatinib is widely used also in very elderly patients with chronic myeloid leukemia (CML) at different doses based on concomitant diseases and physician' judgment. However, data on long-term follow-up of these patients are still lacking. To address this issue, we revised in our retrospective database 233 CML patients aged ≥ 75 years and treated with imatinib frontline in 34 italian hematological centers from 2/2002 to 7/2014. Median age at diagnosis was 78.4 years [interquartile range (IQR) 76.3 - 81.3], there were 113 males (48.5%) and 120 females (51.5%), median WBC, Hb and PLT counts were 45.0 x 109/l (IQR 29.4 - 83.4), 12,4 g/dl (IQR 11.0 - 13.6) and 375 x 109/l (IQR 238 - 680), respectively. Sokal Risk at diagnosis was low in 1 patient (0.4%), intermediate in 149 (67.4%), high in 71 (32.2%) and not evaluable in 12. One or more concomitant diseases requiring specific treatments were present in 225/233 patients (96.5%). Median interval from diagnosis to imatinib start was 0.7 month (IQR 0.2 - 1.4): the initial imatinib dose was 400 mg/day in 161 patients (69.1%), 300 mg/day in 57 (24.5%) and 〈 300 mg/day in 15 (6.4%). According to WHO, a grade 3 - 4 hematological and extra-hematological toxicity was reported in 44 (18.8%) and 41 (17.6%) patients, respectively. As to cumulative response, 13 patients (5.6%) discontinued IM due to early toxicity, 4 (1.7%) were resistant and 2 (0.8%) died from unrelated cause early after IM initiation: the remaining 214 patients (91.9%) achieved a complete haematological response (CHR). Among these 214 patients in CHR, 13 refused any other karyotipic or molecular evaluation, 23 achieved CHR only and 178 (76.4% of all 233 patients) achieved a cytogenetic response (CyR), which was partial in 16 patients and complete (CCyR) in 162 (69.5% of all 233 patients). In addition, among the 162 patients in CCyR, 125 (53.6% of all 233 patients) achieved a molecular response (MolR) (ratio 〈 0.1). A blastic phase occurred in 11 patients (4.7%). After a median follow-up from imatinib start of 45.0 months (IQR 22.3 - 72.0), 70 patients have died (9 from disease progression and 61 from unrelated causes), 16 patients were lost to follow-up and 147 are still alive (115 of them still in treatment with imatinib): 5-year event-free survival (EFS) and overall survival (OS) were 51.4% (CI95% 43.9 - 58.9) and 68.5% (CI95% 61.2 - 75.8), respectively. At univariate analysis, only the initial dose of imatinib (400 vs ≤ 300, p=0.03) was a significant predictive factor for CCyR achievement while only PLT count ≤ 500 x 109/l (p=0.031) was a significant predictive factor for MolR achievement. At multivariate analysis for EFS, achievement of a MolR (OR 0.25, 95%CI 0.14 - 0.43, p 〈 0.001), achievement of a CCyR (OR 0.40, 95%CI 0.23 - 0.67, p=0.001) and spleen enlargement (OR 1.56, 95%CI 1.01 - 2.41, p=0.042) were independent prognostic factors; at multivariate analysis for OS, achievement of a MolR (OR 0.30, 95%CI 0.18 - 0.49, p 〈 0.001), age 〈 80 yrs (OR 0.53, 95%CI 0.33 - 0.86, p=0.011) and male gender (OR 1.80, 95%CI 1.11 - 2.91, p=0.016) were independent prognostic factors. In conclusion, the long term follow-up of very elderly CML patients who started imatinib is very good and justify any effort to treat these patients with standard doses, in order to achieve cytogenetic and molecular responses as in younger subjects. Disclosures Castagnetti: BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Tiribelli:Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis Farma: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau. Gugliotta:BMS: Honoraria; Novartis: Honoraria. Abruzzese:BMS, Novartis, Pfizer, Ariad: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.1598.1598
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 5
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    Very Elderly Patients with Chronic Phase-Chronic Myeloid Leukemia on Imatinib: No Impact of Concomitant Drugs on Complete Cytogenetic Response
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1582-1582
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1582-1582
    Abstract: Tyrosine-kinase inhibitors (TKIs)have completely changed the expected survival of chronic myeloid leukemia (CML) patients which is now approaching that of the general population: a relevant proportion of CML patients are currently elderly or very elderly. Very elderly patients represent generally a small proportion in published experiences. Older CML patients imatinib treated, as it happens in the general population, receive other drug treatments for associated chronic illnesses. Our aim is to assess if and which classes of concomitant drugs have an impact on cytogenetic response in chronic phase (CP)-CML very elderly (age 〉 75 years) patients. Two hundred and twelve very elderly CP-CML patients, imatinib treated at 33 italian hematological institutions have been retrospectively evaluated. Median age at diagnosis was 78.5 years (range 75.0-93.0); 111 (52.4%) were male. Sixty-two (29.2%) were Sokal high risk. Sixty-seven (31.8%) were treated with reduced dose imatinib ( 〈 400 mg/day), and the remaining patients with imatinib 〉 400 mg/day. Concomitant drugs were 1-2 in 73 (34.4%) patients, 3-4 in 59 (27.8%), and 〉 5 in 64 (30.2%); 16 (7.6%) did not assume any concomitant drug. Drugs more frequently used were antiplatelets, assumed by 104 (49.1%) patients, followed by diuretics in 91 (42.9%) patients, proton pump inhibitors (PPIs) in 86 (40.6%), ACE inhibitors in 55 (25.9%), beta blockers in 44 (20.7%), angiotensin II receptors blockers (ARB) in 41 (19.3%), calcium channel blockers in 34 (16%), statins in 25 (11.8%), and alpha blockers in 11 (5.2%). Univariate logistic regression models were computed to assess the association between cytogenetic response after 6 or 12 months of imatinib treatment and number of concomitant drugs or selected drug classes. Statistical analyses were done using JMP 11.1 (SAS Institute Inc., Cary, NC, USA). Complete cytogenetic response (CCyR) was obtained in 124 (58.8%) patients, of whom 70 (33%) within 6 months. Consequently, we focused our study on the impact of number and types of drugs on CCyR rate, which represents the primary therapeutic endpoint in the elderly. Cytogenetic response distribution according to concomitant drugs is reported in table 1. We did not find any significant correlation between number of concomitant drugs, single classes of antihypertensive drugs, antiplatelets, PPIs or statins and CCyR rate at 6 or 12 months. Even though few pharmacokinetic interactions are reported between imatinib and some of medications we considered, this does not seem to have an impact on cytogenetic response rate in our cohort. Indeed, our results confirm the well-known safety and efficacy of imatinib also in very elderly CML patients. Table 1. Cytogenetic response according to concomitant drugs Drug classes Cytogenetic response CCyR 〈 6 months CCyR 7-12 months CCyR 〉 12 months No CCyR Antiplatelets (n=104) 38 (36.5%) 31 (29.8%) 11 (10.6%) 24 (23.1%) Diuretics (n=91) 32 (35.2%) 21 (23.1%) 13 (14.3%) 25 (27.4%) Proton pump inhibitors (n=86) 30 (34.9%) 22 (25.6%) 13 (15.1%) 21 (24.4%) ACE inhibitors (n=55) 19 (34.6%) 11 (20%) 12 (21.8%) 13 (23.6%) Beta blockers (n=44) 18 (40.9%) 11 (25%) 3 (6.8%) 12 (27.3%) Angiotensin II receptor blockers (n=41) 19 (46.3%) 11 (26.8%) 5 (12.3%) 6 (14.6%) Calcium channel blockers (n=34) 10 (29.4%) 7 (20.6%) 6 (17.7%) 11 (32.3%) Statins (n=25) 9 (36%) 7 (28%) 2 (8%) 7 (28%) Alpha blockers (n=11) 4 (36.4%) / 1 (9.1%) 6 (54.5%) Disclosures Castagnetti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Abruzzese:BMS, Novartis, Pfizer, Ariad: Consultancy. Tiribelli:Bristol Myers Squibb: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis Farma: Consultancy, Speakers Bureau. Rosti:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.1582.1582
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 6
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    Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis
    American Society of Hematology ; 2002
    In:  Blood Vol. 100, No. 10 ( 2002-11-15), p. 3484-3488
    Details
    In: Blood, American Society of Hematology, Vol. 100, No. 10 ( 2002-11-15), p. 3484-3488
    Abstract: A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included patients, 181 had known cancer at entry. The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7% (95% CI, 15.6%-25.8%) versus 6.8% (95% CI, 3.9%- 9.7%) in patients without cancer, for a hazard ratio of 3.2 (95% CI, 1.9-5.4) The 12-month cumulative incidence of major bleeding was 12.4% (95% CI, 6.5%-18.2%) in patients with cancer and 4.9% (95% CI, 2.5%-7.4%) in patients without cancer, for a hazard ratio of 2.2 (95% CI, 1.2-4.1). Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation. Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy. These risks correlate with the extent of cancer. Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2002-01-0108
    RVK:
    XA 33000
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2002
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  • 7
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    Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation
    American Society of Hematology ; 2015
    In:  Blood Vol. 125, No. 18 ( 2015-04-30), p. 2855-2864
    Details
    In: Blood, American Society of Hematology, Vol. 125, No. 18 ( 2015-04-30), p. 2855-2864
    Abstract: TSCM are abundant early after allogeneic hematopoietic stem cell transplantation and derive from naive T cells that survived pt-Cy. Pt-Cy allows the generation of donor primary and recall responses in transplanted patients, even in the presence of persistent antigen.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2014-11-608406
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 8
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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:
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 9
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    Thrombotic and Bleeding Complications in Patients with Chronic Lymphocytic Leukemia and Severe COVID-19: A Study of Eric, the European Research Initiative on CLL
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2772-2775
    Details
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2772-2775
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2022-169909
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 10
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    Eltrombopag for the Treatment of Thrombocytopenia of Low and Intermediate-1 IPSS Risk Myelodysplastic Syndromes: Interim Results on Efficacy, Safety and Quality of Life of an International, Multicenter Prospective, Randomized, Trial
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 91-91
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    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 91-91
    Abstract: Background: About 10% of low risk patients with myelodysplastic syndromes (MDS) experience severe thrombocytopenia. Bleeding and the scarce efficacy of platelet (PLT) transfusions drive research in novel treatments. Eltrombopag is an oral agonist of the thrombopoetin-receptor (TPO-R). Its potential in increasing platelet (PLT) counts in low risk MDS has not been evaluated. We present interim results on the efficacy and safety of eltrombopag in inducing PLT responses in patients with low and intermediate-1 International Prognostic Scoring System (IPSS) risk MDS with severe thrombocytopenia in a Phase II, multicentre, prospective, placebo-controlled, single-blind study (EQoL-MDS). Methods: Primary endpoints are safety and efficacy of eltrombopag. Secondary endpoints include changes in quality of life (QoL), PLT transfusion requirement, incidence and severity of bleeding, and survival. Inclusion criteria are adult age; PLT 〈 30 Gi/L; ECOG performance status 〈 4; ineligibility for, relapsed or refractory to other treatments; and naive to TPO-R agonists. Eltrombopag/placebo (2:1) is administered at a 50 mg daily starting dose with 50 mg increases every 2 weeks to maximum 300 mg to target PLT 100 Gi/L. Dose interruptions or reductions are required for PLT 〉 200 Gi/L or adverse events. Study design is shown in the figure. PLT response, assessed at each visit, is defined as Response if: 1) baseline PLT 〉 20 Gi/L: absence of bleeding and increase by at least 30 Gi/L from baseline; 2) baseline PLT 〈 20 Gi/L: PLT 〉 20 Gi/L and increase by at least 100%, not due to PLT transfusions; and Complete Response if PLT≥100 Gi/L and absence of bleeding. QoL scores are analysed by MDS-specific instrument, QOL-E v. 3. Results: Seventy patients (46 on eltrombopag - Arm A, 24 on placebo -Arm B) have been randomized at the time of this report. Mean age is 68.3 (SD 13.0) years, M/F 38/32. ECOG performance status was 0 in 47 cases, 1 in 16 cases, 2 in 7 cases. Ten patients had comorbidities. According to the WHO 2008 classification, 22 patients had refractory cytopenia with unilineage dysplasia, 9 had refractory anemia with ringed sideroblasts, 31 had refractory cytopenia with multilineage dysplasia (of which 15 with ringed sideroblasts), 6 had refractory anemia with excess blasts-1 and 2 were unclassified. IPSS score was low in 48 cases. Mean baseline platelet (PLT) count was 17.1 (SD 8.2) Gi/L, mean hemoglobin level 10.8 (SD 2.5) g/dL and mean white blood cell count was 5.0 (SD 3.8) Gi/L. Twenty-five (36%) patients were red blood cell transfusion-dependent. Thirty-three had a WHO bleeding scale of 1, 2 experienced mild blood loss, 4 a gross blood loss and 1 a debilitating blood loss. Fourteen patients in Arm A and 8 in Arm B had required PLT transfusions in the 8 weeks prior to randomization. Twenty-three cases (50%) in Arm A have responded versus 2 (8%) in Arm B (p=0.001). Thirty-three patients have completed at least 24 weeks of study. Median time to response was 14 days (IQR 7-46 days) at a median daily dose of 75 (IQR 50-162.5 mg). PLT count increased by mean 53.2 (SD 68.1) Gi/L (p=0.001) in Arm A versus no significant changes in Arm B by week 24. QOL-E scores at baseline and 12 weeks in 47 cases in both arms are shown in the table. There was an increase in treatment outcome index,mainly experienced in the first 3 weeks (p=0.034). Fatigue improved from baseline to 12 weeks associated with response (p=0.016). Related Grade III-IV adverse events (AE) occurred in 10 patients (22%) in Arm A and consisted in: nausea (4), hypertransaminasemia (3), hyperbilirubinemia (1), sepsis (1), pruritis (1), heart failure (1), asthenia (1), vomit (1), while in Arm B 1 patient (4 %) experienced grade 3 bone marrow fibrosis. MDS disease progression occurred in 5 (11%) in Arm A versus 2 (8%) in Arm B, p=ns. Conclusions: Preliminary data indicate that lower risk MDS patients with severe thrombocytopenia undergoing treatment with eltrombopag experience significant improvements in PLT counts accompanied by improvements in fatigue. The drug appears to be well-tolerated and not associated with MDS progression. Further follow-up is required to evaluate the impact on survival. Figure 1. Study design Figure 1. Study design Figure 2. QOL-E domains at baseline and 12 weeks between Arm A (eltrombopag) and Arm B (placebo) Figure 2. QOL-E domains at baseline and 12 weeks between Arm A (eltrombopag) and Arm B (placebo) Disclosures Oliva: Novartis: Speakers Bureau; Celgene: Other: Advisory Board, Speakers Bureau; Amgen: Consultancy. Santini:celgene, Janssen, Novartis, Onconova: Honoraria, Research Funding. Palumbo:Novartis: Honoraria, Other: Advisory Board. Fenaux:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.91.91
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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