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  • 1
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 23, No. 3-4 ( 1996-01), p. 227-234
    Materialart: Online-Ressource
    ISSN: 1042-8194 , 1029-2403
    Sprache: Englisch
    Verlag: Informa UK Limited
    Publikationsdatum: 1996
    ZDB Id: 2030637-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2608-2608
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2012
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: British Journal of Haematology, Wiley, Vol. 92, No. 3 ( 1996-02), p. 673-680
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0007-1048 , 1365-2141
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1996
    ZDB Id: 1475751-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Leukemia Research, Elsevier BV, Vol. 33, No. 9 ( 2009-9), p. 1183-1188
    Materialart: Online-Ressource
    ISSN: 0145-2126
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2009
    ZDB Id: 2008028-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: British Journal of Haematology, Wiley, Vol. 95, No. 4 ( 1996-12), p. 678-691
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0007-1048 , 1365-2141
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1996
    ZDB Id: 1475751-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 1994
    In:  Baillière's Clinical Haematology Vol. 7, No. 2 ( 1994-6), p. 263-272
    In: Baillière's Clinical Haematology, Elsevier BV, Vol. 7, No. 2 ( 1994-6), p. 263-272
    Materialart: Online-Ressource
    ISSN: 0950-3536
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1994
    ZDB Id: 2262847-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Walter de Gruyter GmbH ; 2011
    In:  LaboratoriumsMedizin Vol. 35, No. 5 ( 2011-01-01), p. --
    In: LaboratoriumsMedizin, Walter de Gruyter GmbH, Vol. 35, No. 5 ( 2011-01-01), p. --
    Materialart: Online-Ressource
    ISSN: 1439-0477 , 0342-3026
    Sprache: Unbekannt
    Verlag: Walter de Gruyter GmbH
    Publikationsdatum: 2011
    ZDB Id: 2081704-6
    ZDB Id: 2909042-8
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1503-1503
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2012
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Blood, American Society of Hematology, Vol. 130, No. Suppl_1 ( 2017-12-07), p. 897-897
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2017
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 1995
    In:  Transplantation Vol. 59, No. 12 ( 1995-06), p. 1734-1736
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 59, No. 12 ( 1995-06), p. 1734-1736
    Materialart: Online-Ressource
    ISSN: 0041-1337
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 1995
    ZDB Id: 2035395-9
    Standort Signatur Einschränkungen Verfügbarkeit
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