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  • 1
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 9 ( 2022-09), p. 2539-2548
    Abstract: Curative intended treatment is challenging in patients with relapsed or refractory acute myeloid leukemia (r/r AML) and associated with a dismal prognosis for long-term survival. Despite novel treatment options, the majority of patients are treated with chemotherapy-based regimens. Although widely used, little data exist on the combination of fludarabine, cytarabine, granulocyte colony stimulating factor (FLAG) and mitoxantrone as salvage strategy for r/r AML. Materials and methods Sixty-six patients receiving Mito-FLAG for r/r AML treated at a German tertiary care center between 2009 and 2019 were analyzed with regard to response rates, survival and safety profile. Results Overall response rate was 75.8% with 56.1% of patients achieving complete remission (CR) and 19.7% partial remission (PR). After a median follow-up of 54 months, median overall survival (OS) was 13 months. Patients transitioned to allogeneic hematopoietic stem cell transplantation (alloHSCT) (75.8%) showed a significant improvement in OS with a median OS of 17 (95% CI 8.5–25.4) months vs 3 (95% CI 1.7–4.3) months ( p   〈  0.001). 30- and 60-day mortality rates for all patients after the initial cycle of Mito-FLAG were 4.5% and 7.6%, respectively. Conclusion The Mito-FLAG salvage protocol represents an effective and feasible treatment regimen for r/r AML. Importantly, a high rate of transition to successful alloHSCT with the aim of long-term disease-free survival has been shown.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459285-X
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5436-5436
    Abstract: Introduction: Incidence of diffuse large B-cell lymphoma (DLBCL) increases in part due to a growing elderly population. Age, comorbidities and different drug metabolism confer to increased risk for treatment-dependent toxicity. Thus, standard R-CHOP frequently is no treatment option. Therapeutic strategies vary from adapted CHOP-protocols to Bendamustine, both in combination with Rituximab (R). R-mini-CHOP is an attenuated CHOP-regimen with reduced cyclophosphamide and doxorubicin doses that recently has been shown to be a good compromise between efficacy and safety in patients older than 80 years. R-Bendamustine is well established in indolent lymphoma and shows efficacy in small DLBCL series of elderly and co-morbid patients. No comparison between R-mini-CHOP and R-Bendamustine is available. Patients/methods: We retrospectively analyzed 24 consecutive patients with newly diagnosed DLBCL unfit for R-CHOP. All finished firstline therapy. Median observation time was 15 months. Ten patients received R-mini-CHOP and 14 R-Bendamustine (R-B) as 1st line therapy. Baseline characteristics were age, ECOG, comorbidities quantified with the relevant somatic comorbidity index (RSC) based on cumulative illness rating scale for geriatrics (CIRS-G), and risk stratification according to the international prognostic index (IPI). Primary endpoint was progression free survival (PFS), secondary endpoints overall response rate and survival (ORR/OS), rate of complete remission (CR) and graded toxicity according to NCI-CTCAE 4.0. Results: Median age of the 14 R-B treated patients was 83 years (62-92), ECOG score was ≥ 2 in 36%. 50% had an RSC ≥ 3, Ann-Arbor-Stage was ≥ 3 in 57% and IPI was ≥ 3 in 57%. Median age of the 10 R-mini-CHOP patients was 81 years (68-87), ECOG was ≥ 2 in 30%. 40% had an RSC ≥ 3, Ann-Arbor-Stage was ≥ 3 in 70% and IPI was ≥ 3 in 60%. Median 5 (2-9) cycles of R-B and 4 (2-6) cycles of R-mini-CHOP were administered, and 36% vs. 40% reached the planned six cycles. The ORR for R-B was 64% with med. PFS of 6 (2-41) months and med. OS of 15 (4-56) months. The ORR for R-mini-CHOP was 60% with a med. PFS of 6 (2-34) months and med. OS of 8 (3-36) months. 21% (R-B) vs. 20% (R-mini-CHOP) achieved CR. Non hematologic toxicity was mainly grade I and II. Grade III/IV hematologic toxicity occurred in 7% vs. 22% of the administered cycles of R-B/R-mini-CHOP, hence 21% vs. 50% patients were affected. Conclusions: This exploratory retrospective analysis confirms R-B and R-mini-CHOP as reasonable treatment options for 1st line treatment of elderly and comorbid DLBCL-patients. Toxicity was well manageable in both treatment arms. Superior hematologic tolerability of R-B compared to R-mini-CHOP warrants a treatment recommendation in particular for patients with impaired hematologic reserve. However, our data cannot recommend any of both regimens as “winner”. For evidence based decision-making prospective and comparative investigation is required. Disclosures Hammersen: Mundipharma: travel support Other. Off Label Use: Bendamustine in the treatment of agressive Non-Hodgkin Lymphoma. La Rosee:Mundipharma: Honoraria, travel support Other.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC
    Abstract: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. Methods We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. Results Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. Conclusion Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1459285-X
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  • 4
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 6 ( 2022-06), p. 1481-1492
    Abstract: Acute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predicts poor prognosis. Intensive treatment protocols of those high-risk patients should consider allogeneic stem cell transplantation (allo-HSCT) in first complete remission (CR). Despite allo-HSCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AML-MRC) or t-AML based on improved survival and remission rates compared to standard 7 + 3 induction. Patients and methods 110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24–77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing allo-HSCT, reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%). Results Induction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in eight patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0–167), 10 months (0–234) and 15 months (0–234), respectively ( p   〈  0.0001). A significant improvement of OS was observed in patients who underwent allo-HSCT compared to those without subsequent allo-HSCT: 9 vs. 46 months, p   〈  0.0001. Rate of transplantation-related mortality (TRM) in the early phase post allo-HSCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post allo-HSCT (median OS not reached). Conclusion S-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with allo-HSCT after full or reduced-intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459285-X
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  • 5
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e2130832-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2922183-3
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4371-4371
    Abstract: Frail patients with aggressive NHL frequently do not qualify for CHOP-based chemotherapy. Alternatives are required urgently. Bendamustine has been well established as a standard treatment of indolent lymphomas. Its use in high grade lymphoma has been suggested as a promising option. However, which patients benefit most effectively requires further clarification. Methods We retrospectively characterized 51 unselected consecutive patients (39,2% female, 60,8% male, median age 70 years, range 32 - 92 years) with aggressive NHL treated with bendamustine +/- rituximab. They were analyzed for baseline characteristics (histological type, IPI, ABC/GCB-subtypes, age, ECOG, comorbidity (CIRS-G), outcome (ORR, PFS, OS), and toxicity (CTCAE)). Results 21 patients with aggressive NHL received Bendamustin as 1st-line therapy and 30 patients beyond 1st-line. Of the 1st line patients 14 suffered from diffuse large cell B cell lymphoma (DLCBL), 5 from mantle cell lymphoma (MCL), and 2 from other subtypes. In 1st line patients median age was 82 years, ECOG-status was ≥ 2 in 38%. Median international prognostic index (IPI) was 3 (range 1-4). Comorbidity assessment by CIRS-G revealed median 3 (range 1 to 5) severely or very severely affected organs. The overall response rate (ORR) in 1st line treatment was 91%, with a median progression free survival (PFS) of 6 months and a median overall survival (OS) of 15 month. In DLBCL 5 GCB- and 6 ABC-lymphomas were differentiated. GCB-patients showed an ORR of 80% (2 complete remission (CR), 2 partial remission PR)), a median PFS 8 month and OS of 15 months, respectively. ABC-patients had an ORR 67% (no CR, 4 PR, 2 SD), a median PFS of 6 month and OS of 8 months, respectively (n.s.). 7 patients achieved a long term-remission 〉 5 years. Univariate analysis of prognostic variables showed significance for ECOG (p 〈 0.0001) and CIRS-G (p=0.002) for OS, Cox-regression analysis showed significance for ECOG (p=0.016). No significance was shown for disease stage or LDH activities. The ORR in patients beyond 1st-line therapy (median age 64 years, ECOG-status ≥ 2 in 17%) was 66% with a median PFS of 8 month and OS of 24 month. Median cumulative dose was 540 mg/m2 in median 4 cycles. Toxicity in the 1st-line cohort was moderate, mainly grade 1 & 2. Three patients showed grade 3 leukocytopenia. Other side effects primarily were: inappetence, weight-loss, fever. Conclusion Bendamustine shows high efficacy in aggressive NHL, even sustained remission was achieved by a subgroup, which requires further definition. Toxicity was well manageable. Defining prognostic parameters we showed GCB-subtype of DLBCL might predict a better outcome in bendamustine treated patients. Remarkably, performance and comorbidity assessment is of crucial prognostic value with a greater impact on outcome compared to classic parameters. Currently, the BRENDA trial (NCT01686321) prospectively investigates the role of bendamustine in aggressive NHL. Disclosures: Off Label Use: Use of Bendamustine in aggressive NHL. Wedding:Roche: Speakers Bureau; Amgen: Speakers Bureau; Chugai: Speakers Bureau; Janssen-Cilag: Speakers Bureau; Novartis: Speakers Bureau; Cephalon: Speakers Bureau; Prostarkan: Speakers Bureau; Pfizer: Speakers Bureau. La Rosée:Mundi Pharma: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 3 ( 2007-09), p. 861-870
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Issue
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1472120-X
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  • 8
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 11 ( 2022-11), p. 3191-3202
    Abstract: Diagnosis of acute myeloid leukemia (AML) is associated with poor outcome in elderly and unfit patients. Recently, approval of the BCL-2 inhibitor venetoclax (VEN) in combination with hypo-methylating agents (HMA) led to a significant improvement of response rates and survival. Further, application in the relapsed or refractory (r/r) AML setting or in context of allogeneic stem cell transplantation (alloHSCT) seems feasible. Methods and patients Fifty-six consecutive adult AML patients on VEN from January 2019 to June 2021 were analyzed retrospectively. Patients received VEN either as first-line treatment, as subsequent therapy (r/r AML excluding prior alloHSCT), or at relapse after alloHSCT. VEN was administered orally in 28-day cycles either combined with HMA or low-dose cytarabine (LDAC). Results After a median follow-up of 11.5 (range 6.1–22.3) months, median overall survival (OS) from start of VEN treatment was 13.3 (2.2–20.5) months, 5.0 (0.8–24.3) months and 4.0 (1.5–22.1) months for first-line, subsequent line treatment and at relapse post-alloHSCT, respectively. Median OS was 11.5 (10–22.3) months from start of VEN when subsequent alloHSCT was carried out. Relapse-free survival (RFS) for the total cohort was 10.2 (2.2 – 24.3) months. Overall response rate (composite complete remission + partial remission) was 51.8% for the total cohort (61.1% for VEN first-line treatment, 52.2% for subsequent line and 42.8% at relapse post-alloHSCT). Subgroup analysis revealed a significantly reduced median OS in FLT3-ITD mutated AML with 3.4 (1.9–4.9) months versus 10.4 (0.8–24.3) months for non-mutated cases, (HR 4.45, 95% CI 0.89–22.13, p  = 0.0002). Patients harboring NPM1 or IDH1/2 mutations lacking co-occurrence of FLT3-ITD showed a survival advantage over patients without those mutations (11.2 (5–24.3) months versus 5.0 (0.8–22.1) months, respectively, (HR 0.53, 95% CI 0.23 – 1.21, p  = 0.131). Multivariate analysis revealed mutated NPM1 as a significant prognostic variable for achieving complete remission (CR) (HR 19.14, 95% CI 2.30 – 436.2, p   〈  0.05). The most common adverse events were hematological, with grade 3 and 4 neutropenia and thrombocytopenia reported in 44.6% and 14.5% of patients, respectively. Conclusion Detailed analyses on efficacy for common clinical scenarios, such as first-line treatment, subsequent therapy (r/r AML), and application prior to and post-alloHSCT, are presented. The findings suggest VEN treatment combinations efficacious not only in first-line setting but also in r/r AML. Furthermore, VEN might play a role in a subgroup of patients with failure to conventional chemotherapy as a salvage regimen aiming for potential curative alloHSCT.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459285-X
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  • 9
    Online Resource
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    Springer Science and Business Media LLC ; 2023
    In:  Journal of Cancer Research and Clinical Oncology Vol. 149, No. 4 ( 2023-04), p. 1569-1583
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 149, No. 4 ( 2023-04), p. 1569-1583
    Abstract: Infectious complications reflect a major challenge in the treatment of patients with acute myeloid leukemia (AML). Both induction chemotherapy and epigenetic treatment with hypomethylating agents (HMA) are associated with severe infections, while neutropenia represents a common risk factor. Here, 220 consecutive and newly diagnosed AML patients were analyzed with respect to infectious complications dependent on treatment intensity and antifungal prophylaxis applied to these patients. Patients and methods We retrospectively analyzed 220 patients with newly diagnosed AML at a tertiary care hospital between August 2016 and December 2020. The median age of AML patients undergoing induction chemotherapy ( n  = 102) was 61 years (25–76 years). Patients receiving palliative AML treatment ( n  = 118) had a median age of 75 years (53–91 years). We assessed the occurrence of infectious complication including the classification of pulmonary invasive fungal disease (IFD) according to the EORTC/MSG criteria at diagnosis and until day 100 after initiation of AML treatment. Furthermore, admission to intensive care unit (ICU) and subsequent outcome was analyzed for both groups of AML patients, respectively. Results AML patients subsequently allocated to palliative AML treatment have a significantly higher risk of pneumonia at diagnosis compared to patients undergoing induction chemotherapy (37.3% vs. 13.7%, P   〈  0.001) including a higher probability of atypical pneumonia (22.0% vs. 10.8%, P  = 0.026). Furthermore, urinary tract infections are more frequent in the palliative subgroup at the time of AML diagnosis (5.1% vs. 0%, P  = 0.021). Surprisingly, the incidence of pulmonary IFD is significantly lower after initiation of palliative AML treatment compared to the occurrence after induction chemotherapy (8.4% vs. 33.3%, P   〈  0.001) despite only few patients of the palliative treatment group received Aspergillus spp. -directed antifungal prophylaxis. The overall risk for infectious complications at AML diagnosis is significantly higher for palliative AML patients at diagnosis while patients undergoing induction chemotherapy have a significantly higher risk of infections after initiation of AML treatment. In addition, there is a strong correlation between the occurrence of pneumonia including atypical pneumonia and pulmonary IFD and the ECOG performance status at diagnosis in the palliative AML patient group. Analysis of intensive care unit (ICU) treatment (e.g. in case of sepsis or pneumonia) for both subgroups reveals a positive outcome in 10 of 15 patients (66.7%) with palliative AML treatment and in 15 of 18 patients (83.3%) receiving induction chemotherapy. Importantly, the presence of infections and the ECOG performance status at diagnosis significantly correlate with the overall survival (OS) of palliative AML patients (315 days w/o infection vs. 69 days with infection, P 0.0049 and 353 days for ECOG  〈  1 vs. 50 days for ECOG  〉  2, P   〈  0.001, respectively) in this intent-to-treat analysis. Conclusion The risk and the pattern of infectious complications at diagnosis and after initiation of AML therapy depends on age, ECOG performance status and subsequent treatment intensity. A comprehensive diagnostic work-up for identification of pulmonary IFD is indispensable for effective treatment of pneumonia in AML patients. The presence of infectious complications at diagnosis contributes to an inferior outcome in elderly AML patients.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1459285-X
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 19 ( 2013-07-01), p. e312-e315
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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