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  • 1
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    Acute Myeloid Leukemia with Translocation (8;21). Cytomorphology, Dysplasia and Prognostic Factors in 41 Cases
    Informa UK Limited ; 1996
    In:  Leukemia & Lymphoma Vol. 23, No. 3-4 ( 1996-01), p. 227-234
    Details
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 23, No. 3-4 ( 1996-01), p. 227-234
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    URL: Article
    DOI: 10.3109/10428199609054825
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1996
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  • 2
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    Long Term Follow-up of 121 Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Treated in Prospective GMALL Trials Supports a Greater Emphasis On Allogeneic SCT as Definitive Postremission Therapy.
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 2608-2608
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2608-2608
    Abstract: Abstract 2608 Background: Combined treatment with a tyrosine kinase inhibitor (TKI) and ALL-type induction and consolidation chemotherapy followed by allogeneic SCT is standard front-line therapy for younger patients with Ph+ALL, but the value of adding intensive chemotherapy to a TKI in elderly patients is controversial. More than 90% of elderly patients achieve a complete remission, irrespective of the type of TKI-based induction, but relapse is the major cause of treatment failure. In a previously reported randomized trial examining imatinib combined with intensive induction and consolidation chemotherapy for Ph+ALL in elderly patients (n=55), the probability of overall survival (OS) after 24 months was 42% ± 8% (Ottmann OG et al., Cancer. 2007; 109:2068-76). To date, very little published data on long-term outcome of elderly patients with Ph+ALL are available. Aims: We conducted the present analysis to determine whether subsets of patients derive long-term benefit from combined imatinib plus intensive chemoptherapy, examine the characteristics of long-term survivors, determine whether such patients can be identified by assessment of MRD, and obtain preliminary results on the feasibility and efficacy of SCT in this population of elderly patient. Study design and patients demographics: Our current analysis includes a total of 121 patients (119 ALL, 2 CML in lymphoid blast crisis), with a median age of 66 years (range 54–80). Fifty-five patients were enrolled in a previously reported randomized clinical trial comparing single-agent imatinib and chemotherapy as induction therapy, followed by up to 6 cycles of consolidation chemotherapy; a further 67 patients were subsequently treated according to this protocol as per recommendation by the GMALL Study Group. Results: The overall CR rate was 88%, median time to progression was 14.5 months (range 0.5–102) and OS was 18.6 months (range 0.5–102), respectively. Probabilities of remission duration, survival and TTP at 5 years were 19%, 22% and 19%, respectively. The type of initial induction therapy had no significant impact on OS and DFS. Of 113 pts, who were evaluable for comorbities, pulmonary disease was the only comorbidity associated with inferior outcome (median OS 13 months vs. 20 months, univariate analysis p=0.02). Allogeneic SCT was performed in CR1 in 12 patients and as salvage therapy in another 7 patients. Median age of these 19 patients was 62y (range 54–69). The time from diagnosis to SCT in CR1 was 4.6 months (2.9 mo – 16.8 mo) and from relapse to SCT in 〉 CR1 3 months (2.1 mo – 6.1 mo). The 5yr OS in patients transplanted in CR1 vs. non-transplanted patients was superior (48% vs 22%). Remarkably, OS of the 7 patients transplanted beyond CR1 as part of salvage therapy was 43% after 4.5 years. With a median follow-up of 21.6 months (range 3.3– 54) after SCT, 8 patients are in ongoing CR with a median OS of 51.8 months from initial diagnosis (range 35 – 66), 5 pts. died in CR, 6 pts. relapsed. Conclusions: The combination of imatinib with intensive chemotherapy is feasible in elderly patients, but long-term survival is poor primarily due to high relapse rate. Allogeneic SCT in CR1 is superior to conventional therapy and should be considered as front-line therapy in this elderly patient population. The encouraging results of allogeneic SCT performed beyond CR1 suggest that SCT should be considered as definite postremission therapy in a larger proportion of elderly patients than is current practice. Disclosures: Ottmann: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.2608.2608
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 3
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    Secondary acute leukaemias with 11q23 rearrangement: clinical, cytogenetic, FISH and FICTION studies
    Wiley ; 1996
    In:  British Journal of Haematology Vol. 92, No. 3 ( 1996-02), p. 673-680
    Details
    In: British Journal of Haematology, Wiley, Vol. 92, No. 3 ( 1996-02), p. 673-680
    Abstract: Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML), FAB M5a, one had pro‐B‐acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19–20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL‐1 gene on 11q23 confirmed that in each case the ALL‐1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topoisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. ALL with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for 〉 19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL‐1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL‐1 rearrangement expressed CD34. Moreover, the pro‐B‐ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Article
    DOI: 10.1046/j.1365-2141.1996.00399.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 1996
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  • 4
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    Amifostine has the potential to induce haematologic responses and decelerate disease progression in individual patients with low- and intermediate-1-risk myelodysplastic syndromes
    Elsevier BV ; 2009
    In:  Leukemia Research Vol. 33, No. 9 ( 2009-9), p. 1183-1188
    Details
    In: Leukemia Research, Elsevier BV, Vol. 33, No. 9 ( 2009-9), p. 1183-1188
    Type of Medium: Online Resource
    ISSN: 0145-2126
    URL: Article
    DOI: 10.1016/j.leukres.2009.03.027
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
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  • 5
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    Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia
    Wiley ; 1996
    In:  British Journal of Haematology Vol. 95, No. 4 ( 1996-12), p. 678-691
    Details
    In: British Journal of Haematology, Wiley, Vol. 95, No. 4 ( 1996-12), p. 678-691
    Abstract: The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 〉 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD; 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%; MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 〉 50 achieved CR, and the overall survival was superior to all other Ph‐positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid‐associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph‐positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph‐positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Article
    DOI: 10.1046/j.1365-2141.1996.d01-1968.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 1996
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  • 6
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    3 Morphology and cytochemistry of acute lymphoblastic leukaemia
    Elsevier BV ; 1994
    In:  Baillière's Clinical Haematology Vol. 7, No. 2 ( 1994-6), p. 263-272
    Details
    In: Baillière's Clinical Haematology, Elsevier BV, Vol. 7, No. 2 ( 1994-6), p. 263-272
    Type of Medium: Online Resource
    ISSN: 0950-3536
    URL: Article
    DOI: 10.1016/S0950-3536(05)80202-1
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1994
    detail.hit.zdb_id: 2262847-2
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  • 7
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    Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial
    American Society of Hematology ; 2003
    In:  Blood Vol. 101, No. 1 ( 2003-01-01), p. 64-70
    Details
    In: Blood, American Society of Hematology, Vol. 101, No. 1 ( 2003-01-01), p. 64-70
    Abstract: Risk assessment in acute myeloid leukemia (AML) using pretreatment characteristics may be improved by incorporating parameters of early response to therapy. In the 1992 trial of the German AML Cooperative Group (AMLCG), the amount of residual leukemic blasts in bone marrow was assessed one week after the first induction course (day 16 blasts). A total of 449 patients 16 to 76 years of age (median, 53 years) with de novo AML entered the trial and were evaluable. Treatment included TAD/HAM (thioguanine, cytosine arabinoside, and daunorubicin/high-dose cytosine arabinoside and mitoxantrone) double induction, TAD consolidation, and randomly either maintenance therapy or S-HAM consolidation. Cytogenetics were favorable, intermediate, unfavorable and not available in 10.0%, 48.3%, 13.1%, and 28.5%, respectively. Day 16 blasts ranged from 0% to 100% (median, 5%, mean ± SD, 18.6 ± 28.5%). Complete remission (CR) rate was 72.6%, 17.6% had persistent leukemia (PL), and 9.8% succumbed to hypoplastic death. Median overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were 18, 9, and 15 months with 28.4%, 21.6%, and 30.1% at 5 years, respectively. As a continuous variable, day 16 blasts were related to CR rate (P  & lt; 0.0001), PL rate (P  & lt; 0.0001), OS (P  & lt; 0.0001), EFS (P  & lt; 0.0001), and RFS (P = 0.0049). Multivariate analyses identified the following parameters to be associated with the respective end points. CR rate: day 16 blasts (P  & lt; .0001), age (P = .0036), and LDH (P = .0072); OS: unfavorable cytogenetics (P  & lt; .0001), day 16 blasts (P  & lt; .0001), age (P  & lt; .0001), and LDH (P = .0040); EFS: unfavorable cytogenetics (P  & lt; .0001), LDH (P  & lt; .0001), day 16 blasts (P  & lt; .0001), and age (P = .0061); RFS: unfavorable cytogenetics (P  & lt; .0001), LDH (P  & lt; .0001), and day 16 blasts (P = .0359). The prognostic significance of day 16 blasts is independent of pretherapeutic parameters and predicts outcome even in patients achieving a CR.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood-2002-02-0532
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2003
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  • 8
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    Imatinib (IM) and Interferon-Alpha (IFN-a) Maintenance Therapy Is Associated with Long-Term DFS in a Subset of Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL)
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1503-1503
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1503-1503
    Abstract: Abstract 1503 Background: The frequent development of acquired resistance in patients with Ph+ALL initially responsive to tyrosine kinase inhibitor(TKI)-based regimens highlights the need for more effective post-remission therapy. Imatinib or dasatinib as single agents or combined with chemotherapy are commonly employed, but do not adequately prevent relapse. Interferon-alpha as treatment for bcr-abl positive leukemias has attracted renewed interest, fueled by preclinical observations suggesting that IFN-a may target leukemic stem cells. Proposed mechansims of IFN-a action include recruitment of dormant CML stem cells into the cell cycle, enhancing their susceptibility to eradication by TKIs. Whereas several recent randomized clinical studies in CML demonstrate greater efficacy of combined IFN-a and TKI compared to TKIs alone, no long-term clinical data on the combination of IFN-a and TKIs are available for patients with Ph+ALL. Aims: This prospective, open-label phase II study was designed to investigate the combination of low-dose IFN-a with imatinib mesylate (IM) 600mg daily as maintenance therapy in Ph+ALL patients in terms of hematologic and non-hematologic toxicity and the ability to adhere to the planned dose of the study drugs. In addition, we examined whether bcr-abl transcript levels and mutation status were predictive of relapse and remission duration. Outcome with study treatment is compared with that of patients with Ph+ALL who received the same initial therapy, followed by maintenance with imatinib alone. Patients and study design: Patients with Ph+ALL in first CR after receiving induction and consolidation chemotherapy according the GMALL protocol for elderly Ph+ALL who were not candidates for allogeneic stem cell transplantation (SCT). were eligible. MT consisted of IM at a single dose of 600 mg daily, combined with low dose subcutaneous interferon-alfa-2a (RoferonÒ) starting at 1 MU three times a week with dose escalation to a target dose of 3 MU three times a week as rapidly as tolerated. The trial was approved by the Ethics Committee of the University of Frankfurt, Germany. Results: 19 elderly patients (median age 66 yrs; [60 – 75 yrs]) were enrolled in the combination study, 12 patients (median age 67 yrs; [58 – 75 yrs] ) who received only IM as recommended MT after the same front-line therapy served as a control group. The median overall duration of MT is 26 mos. [3 – 110 mos] . Median overall survival for pts. receiving IM+ IFN-a is 5.4 yrs [2.5 – 11.4 yrs] vs. 2.9 yrs. [0.7 – 8.7 yrs] for pts. receiving IM alone (p=ns). For pts. receiving IM+ IFN-a, the median remission duration from start of maintenance is 2.2 yrs. [0.4–9.5 yrs] versus 0.75 yrs[0.1–7.6 yrs] . for patients receiving IM as MT (p=0.07). Three of 19 pts. are in ongoing CR 7.9, 8.6, and 10.4 years after start of maintenance. 4 pts. died in CR of causes unrelated to leukemia and 12 patients relapsed, 2 (16%) with isolated CNS involvement. Remission duration was independent of the number of previous cycles of intensive chemotherapy, of the MRD response during the first 6 mos. of intensive front-line therapy (16 mos. vs. 26 mos.) and of achievement of PCR negativity at any time during intial therapy. Surprisingly, the BCR-ABL transcript level at the start of MT likewise had no impact on time to disease recurrence. Prolonged MRD positivity without hematologic relapse occured in several patients. For pts. receiving IM as MT, 2 of 12 pts. are in ongoing CR 6.5 and 7.6 yrs. from start of maintenance. 2 of the 10 patients relapsed on MT with CNS involvement. Overall tolerability was acceptable, adverse events which lead to dose reductions for IFN-a were noted in 9 of 18 evaluable pts. Nine pts. suffered from moderate depression or fatigue. Hematologic toxicity during MT with IM+ IFN-a was mild with grade III cytopenia developing in only 2 pts. Conclusions: In elderly Ph+ALL pts. ineligible for allogeneic SCT, maintenance with IM in combination with low-dose IFN-a results in long-term sustained remissions in a substantial proportion of patients, with acceptable side effects. Surprisingly, the level of MRD was not predictive for remission duration. The lack of relationship between number of consolidation cycles and remission duration suggests IM+IFN-a MT may be effective even if started earlier during front-line therapy. Evaluation of the more potent 2nd generation TKI in combination with LD IFN-a as MT for Ph+ALL is warrented. Disclosures: Ottmann: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.1503.1503
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 9
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    Morphologic Dysplasia in De Novo Acute Myeloid Leukemia (AML) Is Related to Unfavorable Cytogenetics but Has No Independent Prognostic Relevance Under the Conditions of Intensive Induction Therapy: Results of a Multiparameter Analysis From the German AML Cooperative Group Studies
    American Society of Clinical Oncology (ASCO) ; 2003
    In:  Journal of Clinical Oncology Vol. 21, No. 2 ( 2003-01-15), p. 256-265
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 21, No. 2 ( 2003-01-15), p. 256-265
    Abstract: Purpose: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. Patients and Methods: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. Results: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P 〈 .001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P 〈 .001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. Conclusion: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2003.08.005
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2003
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  • 10
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    Final Evaluation of Randomized CML-Study IV: 10-Year Survival and Evolution of Terminal Phase
    American Society of Hematology ; 2017
    In:  Blood Vol. 130, No. Suppl_1 ( 2017-12-07), p. 897-897
    Details
    In: Blood, American Society of Hematology, Vol. 130, No. Suppl_1 ( 2017-12-07), p. 897-897
    Abstract: Background Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). Methods From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. The impact of patients' and disease factors on survival was prospectively analyzed. At the time of evaluation, at least 62% of patients still received imatinib, 26.2% were switched to 2nd generation tyrosine kinase inhibitors. Results After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival 80% and 10-year relative survival 92%. In spite of a faster response with IM800mg, the survival difference between IM400mg and IM800mg was only 3% at 5 years. In a multivariate analysis, the influence on survival of risk-group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs. other) was significant in contrast to any form of initial treatment optimization. Patients that reached the response milestones 3, 6 and 12 months, had a significant survival advantage of about 6% after 10 years regardless of therapy. The progression probability to blast crisis was 5.8%. Blast crisis was proceeded by high-risk additional chromosomal aberrations. Conclusions For responders, monotherapy with IM400mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease and blast crisis, more life-time can currently be gained by carefully addressing non-CML determinants of survival. Disclosures Hehlmann: Novartis: Research Funding; BMS: Consultancy. Saussele: Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Pfirrmann: BMS: Honoraria; Novartis: Honoraria. Krause: Novartis: Honoraria. Baerlocher: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Bruemmendorf: Novartis: Research Funding. Müller: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Jeromin: MLL Munich Leukemia Laboratory: Employment. Hänel: Roche: Honoraria; Novartis: Honoraria. Burchert: BMS: Honoraria. Waller: Mylan: Consultancy, Honoraria. Mayer: Eisai: Research Funding; Novartis: Research Funding. Link: Novartis: Honoraria. Scheid: Novartis: Honoraria. Schafhausen: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Hochhaus: Incyte: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; ARIAD: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V130.Suppl_1.897.897
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2017
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