142 results on '"Hoogendoorn, Mels"'
Search Results
102. Prognostic Importance of Comorbidity in a Population-Based Analysis of Patients with Advanced-Stage Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP
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Wieringa, André, primary, van Roon, Eric N., additional, Joosten, Peter, additional, Beerden, Tim, additional, Storm, Huib, additional, Kibbelaar, Robby, additional, Kluin-Nelemans, Hanneke C., additional, Veeger, Nic J.G.M., additional, and Hoogendoorn, Mels, additional
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- 2012
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103. A Significant Better Two Year Survival in the Very Elderly Patients with a Diffuse Large B-Cell Lymphoma (DLBCL) Who Did Complete Standard Therapy: A Population-Based Cohort Study On Treatment, Toxicity and Outcome.
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Boslooper, Karin, primary, Joosten, Peter, additional, Veeger, Nic J.G.M., additional, Kibbelaar, Robby, additional, van Roon, Eric, additional, Hovenga, Sjoerd, additional, Woolthuis, Gerhard, additional, Kluin-Nelemans, Hanneke C., additional, and Hoogendoorn, Mels, additional
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- 2012
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104. R-DHAP Immuno-Chemotherapy Is An Effective Remission-Induction Treatment for Fludarabine Refractory CLL Patients and Allows the Majority to Proceed to Allogeneic Stem Cell Transplantation. Results of the Planned Interim Analysis of the Dutch-Belgian Prospective Multicenter HOVON88 Trial,
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Van Gelder, Michel, primary, Ghidey, Wendim, additional, Chamuleau, Martine ED, additional, Cornelissen, Jan J, additional, Wu, Ka Lung, additional, Hoogendoorn, Mels, additional, Daenen, S. M. G. J., additional, Petersen, Eefke, additional, and van Oers, Marinus H. J., additional
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- 2011
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105. Platelet Doubling After the First Azacitidine Cycle Is a Promising Predictor for Response in MDS, CMML and AML Patients in the Dutch Azacitidine Compassionate Patient Named Program,
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Huls, Geert A, primary, van der Helm, Lieke H., additional, Alhan, Canan, additional, Wijermans, P.W., additional, van Marwijk Kooy, Marinus, additional, Schaafsma, Martijn R., additional, Biemond, Bart J, additional, Beeker, Aart, additional, Hoogendoorn, Mels, additional, van Rees, Bastiaan P., additional, de Weerdt, Okke, additional, Wegman, Jurgen, additional, Libourel, Eduard J, additional, Luykx-de Bakker, Sylvia A., additional, Minnema, Monique C., additional, Brouwer, Rolf, additional, Croon-de Boer, Fransien, additional, Eefting, Matthias, additional, Jie, Kon-Siong G., additional, van der Loosdrecht, Arjan A., additional, Koedam, Jan, additional, Veeger, Nic J.G.M., additional, and Vellenga, Edo, additional
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- 2011
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106. Influence of Prophylactic Platelet Transfusions on the Recovery of Bone Marrow Function After Intensive Chemotherapy for Acute Myeloid Leukemia.
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Kivit, Roland MH, primary, Joosten, Peter, additional, Hoogendoorn, Mels, additional, and De Wolf, Joost TM, additional
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- 2010
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107. Unsuccessful Treatment with Lenalidomide in a Diamond-Blackfan Anemia Patient.
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Joosten, Peter, primary, Hoogendoorn, Mels, additional, Storm, Huib, additional, and Kibbelaar, Robby, additional
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- 2009
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108. Early Detection and Rapid Isolation of Leukemia-Reactive Donor T Cells for Adoptive Transfer Using the IFN-γ Secretion Assay
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Jedema, Inge, primary, Meij, Pauline, additional, Steeneveld, Esther, additional, Hoogendoorn, Mels, additional, Nijmeijer, Bart A., additional, van de Meent, Marian, additional, van Luxemburg-Heijs, Simone A.P., additional, Willemze, Roel, additional, and Falkenburg, J.H. Frederik, additional
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- 2007
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109. HemoBase: A Multidisciplinary Registration Systeem in Hemato-Oncology.
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Joosten, Peter, primary, Hoogendoorn, Mels, additional, Storm, Huib, additional, and Kibbelaar, Robby E., additional
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- 2006
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110. A Two Step Nonmyeloablative Allogeneic Transplantation Protocol Using In Vitro T-Cell Depleted Mobilized Stem Cells Followed by Donor Lymphocyte Infusions in Patients with Advanced CLL.
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Barge, Renee M.Y., primary, Hoogendoorn, Mels, primary, Marijt, Erik W.A., primary, Beaumont, Floor, primary, Starrenburg, Ingrid, primary, Smit, Willem, primary, Posthuma, Ward, primary, Fibbe, Willem E., primary, Falkenburg, Frederik, primary, and Willemze, Roelof, primary
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- 2005
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111. Primary Allogeneic T-Cell Responses against Mantle Cell Lymphoma Antigen-Presenting Cells for Adoptive Immunotherapy after Stem Cell Transplantation
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Hoogendoorn, Mels, primary, Olde Wolbers, Judith, additional, Smit, Willem M., additional, Schaafsma, M. Ronald, additional, Jedema, Inge, additional, Barge, Renee M.Y., additional, Willemze, Roel, additional, and Falkenburg, J.H. Frederik, additional
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- 2005
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112. Primary Epstein-Barr virus infection diffusing F18- fluorodeoxyglucose-positron emission tomography/computed tomography response monitoring of Hodgkin's disease: a case report.
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Balink, Hans and Hoogendoorn, Mels
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LYMPHOMAS , *CELL transplantation , *STEM cell transplantation , *POSITRON emission tomography , *COMPUTED tomography - Abstract
Introduction Hodgkin's disease is highly curable by radiotherapy and/or chemotherapy, but refractory disease or early relapses are rarely cured by conventional salvage therapy. Case presentation We report a case of a 20-year-old Caucasian man, with a biopsy-proven intrapulmonary relapse of Hodgkin's disease, for whom salvage chemotherapy was administered. During salvage chemotherapy intense increased F18-fluorodeoxyglucose uptake was noticed in multiple lymph nodes and diffuse increased splenic uptake, suggesting chemotherapyrefractory disease. However, additional information obtained from the patient revealed he recently had met his first girlfriend. An asymptomatic primary Epstein-Barr virus infection was considered proven. Conclusions Interim F18-fluorodeoxyglucose-positron emission tomography/computed tomography is a strong prognostic factor for advanced Hodgkin's and may better identify those patients needing intensified chemotherapy. Related to the nonspecificity of F18-fluorodeoxyglucose, clinical awareness of the potential interference of intercurrent asymptomatic viral infections with treatment and remission status monitoring continues to be important in the interpretation of equivocal medical imaging results. [ABSTRACT FROM AUTHOR]
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- 2014
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113. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma: a population-based cohort study on treatment, toxicity and outcome.
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Boslooper, Karin, Kibbelaar, Robby, Storm, Huib, Veeger, Nic J. G. M., Hovenga, Sjoerd, Woolthuis, Gerhard, van Rees, Bas, de Graaf, Elly, van Roon, Eric, Kluin-Nelemans, Hanneke C., Joosten, Peter, and Hoogendoorn, Mels
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OLDER patients ,LYMPHOMAS ,B cells ,RITUXIMAB ,CYCLOPHOSPHAMIDE ,DOXORUBICIN ,VINCRISTINE ,PREDNISOLONE - Abstract
To assess treatment strategies, toxicity and outcome in very elderly patients (aged ≥ 75 years) diagnosed with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, an observational population-based cohort study was performed. From 103 patients with a median age of 81 years, data of clinical characteristics, treatment, toxicity and outcome were evaluated. Advanced stage DLBCL was documented in 74 patients. In 80 patients chemotherapy was initiated; 70 patients received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). In this group, 39 patients completed all cycles and 30 patients achieved a complete remission. Severe chemotherapy-related toxicity occurred in 69%. Two-year overall survival was 70% for elderly patients who completed chemotherapy, 28% for those treated with incomplete or suboptimal chemotherapy and 21% for those receiving palliative radiotherapy or supportive care. In conclusion, the ability to complete R-CHOP was associated with better overall survival compared to other treatment strategies at the expense of severe treatment-related toxicity. [ABSTRACT FROM AUTHOR]
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- 2014
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114. Progressive multifocal leukoencephalopathy during treatment with rituximab and CHOP chemotherapy in a patient with a diffuse large B-cell lymphoma.
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Sikkema, Tineke, Schuiling, Wouter Jan, and Hoogendoorn, Mels
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DIFFERENTIAL diagnosis ,PROGRESSIVE multifocal leukoencephalopathy diagnosis ,B cell lymphoma ,BIOPSY ,CANCER chemotherapy ,COMBINATION drug therapy ,DISEASE progression ,PROGRESSIVE multifocal leukoencephalopathy - Abstract
A 74-year-old woman with a diffuse large B-cell lymphoma was treated with rituximab and CHOP chemotherapy. After three cycles of chemotherapy she developed progressive symptoms of motor imbalance, fatigue, weight loss and impaired cognitive function, which was interpreted as toxicity of the CHOP chemotherapy. The sixth cycle CHOP chemotherapy was withheld and three additional cycles of rituximab were given. Two weeks later, neurological symptoms appeared, including abducens nerve palsy of her left eye, ataxia and hemiparesis of her right body. MRI of the brain revealed two hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery images without oedema or gadolinium enhancement. A PCR on John Cunningham (JC) virus DNA in cerebrospinal fluid was negative, but subsequent brain biopsy diagnosed progressive multifocal leukoencephalopathy (PML). She rapidly deteriorated and died. Awareness of PML during immunosuppressive therapy can be lifesaving, since only immune reconstitution can prevent mortality in these patients. [ABSTRACT FROM AUTHOR]
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- 2013
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115. Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells
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van Bruggen, J.A.C., van der Windt, G.J.W., Hoogendoorn, Mels, Dubois, J., Kater, Arnon P., and Peters, F.S.
- Abstract
Acquired T-cell dysfunction is characteristic of CLL and is associated with reduced efficacy of T-cell based therapies. A recently described feature of dysfunctional CLL-derived CD8 T cells is reduced metabolic plasticity. To what extend CD4 T cells are affected, and if CD4 T-cell metabolism and function can be restored upon clinical depletion of CLL cells is currently unknown. Here we address these unresolved issues by a comprehensive phenotypic, metabolic, transcriptomic and functional analysis of CD4 T cells of untreated CLL patients, and by analyzing the effects of venetoclax + obinutuzumab on the CD4 population. Resting CD4 T cells derived from CLL patients expressed lower levels of GLUT-1, displayed deteriorated oxidative phosphorylation (OXPHOS) and overall reduced mitochondrial fitness. Upon T-cell stimulation, CLL T cells were unable to initiate glycolysis. Transcriptome analysis revealed that depletion of CLL cells in vitroresulted in upregulation of OXPHOS and glycolysis pathways and restored T-cell function in vitro. Analysis of CD4 T cells from CLL patients prior and after venetoclax + obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells which lead to reduced CD4 T-cell functionality. This trial is registered in the Netherlands Trial Registry ID: NTR6043.
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- 2022
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116. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial
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Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J
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hemic and lymphatic diseases ,610 Medizin und Gesundheit ,3. Good health - Abstract
Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
117. Very late recovery of dapsone-induced methemoglobinemia.
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Wieringa, Andre, Bethlehem, Carina, Hoogendoorn, Mels, van der Maten, Jan, and van Roon, Eric N.
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METHEMOGLOBINEMIA ,DAPSONE ,THERAPEUTICS - Abstract
A letter to the editor is presented which discusses a case of dapsone-induced methemoglobinemia having prolonged recovery period.
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- 2014
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118. Efficacy and Safety of First-Line Therapy with Chlorambucil, Rituximab and Individualized Dose Lenalidomide in FCR-Unfit Patients with Advanced Chronic Lymphocytic Leukemia (CLL): A Phase I/II HOVON Trial
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Kater, Arnon P., Van Oers, Marinus H.J. H.J., Norden, Yvette, Liu, Roberto D., Schipperus, Martin R., Chamuleau, Martine, Nijland, Marcel, Doorduijn, Jeanette K., van Gelder, Michel, Hoogendoorn, Mels, Croon-de Boer, Fransien, Wittebol, Shulamit, Kerst, Martijn, Marijt, Willem, Posthuma, Ward, Raymakers, Reinier, Schaafsma, Ron, Dobber, Johan, Kersting, Sabina, and Levin, Mark-David
- Abstract
Introduction.Since publication of the pivotal CLL011 phase 3 trial, combination of chlorambucil and anti-CD20 MAb has become the standard first-line CLL treatment for patients unfit for FCR. Lenalidomide (Len) has been proven effective both as monotherapy and in combination with rituximab. Although recent studies in CLL suggest that Len is mostly beneficial as consolidation treatment, the exact place and duration of this drug is still not optimized. Moreover, Len has shown a distinct and more difficult to manage toxicity profile in the context of CLL, potentially hampering combination treatment with this drug. We therefore conducted a phase 2 study to evaluate efficacy and safety of a combination of chlorambucil, rituximab and individual dosed Len (induction-I) followed by 6 months of Len monotherapy (induction-II).
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- 2017
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119. Fatal Cobalt Toxicity after a Non-Metal-on-Metal Total Hip Arthroplasty
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M. Peters, Rinne, Willemse, Pax, C. Rijk, Paul, Hoogendoorn, Mels, and P. Zijlstra, Wierd
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This case illustrates the potential for systemic cobalt toxicity in non-metal-on-metal bearings and its potentially devastating consequences. We present a 71-year-old male with grinding sensations in his right hip following ceramic-on-ceramic total hip arthroplasty (THA). After diagnosing a fractured ceramic liner, the hip prosthesis was revised into a metal-on-polyethylene bearing. At one year postoperatively, X-rays and MARS-MRI showed a fixed reversed hybrid THA, with periarticular densities, flattening of the femoral head component, and a pattern of periarticular metal wear debris and pseudotumor formation. Before revision could take place, the patient was admitted with the clinical picture of systemic cobalt toxicity, supported by excessively high serum cobalt and chromium levels, and ultimately died. At autopsy dilated cardiomyopathy as cause of death was hypothesized. A third body wear reaction between ceramic remnants and the metal femoral head very likely led to excessive metal wear, which contributed systemic cobalt toxicity leading to neurotoxicity and heart failure. This case emphasizes that fractured ceramic-on-ceramic bearings should be revised to ceramic-on-ceramic or ceramic-on-polyethylene bearings, but not to metal-on-polyethylene bearings. We aim to increase awareness among orthopedic surgeons for clinical clues for systemic cobalt intoxication, even when there is no metal-on-metal bearing surface.
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- 2017
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120. Effectiveness of a vitamin D regimen in deficient multiple myeloma patients and its effect on peripheral neuropathy.
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Oortgiesen, Berdien E., Dekens, Marloes, Stapel, Ruud, Alheraky, Abdulrazzaq, Dannenberg, Pauline de Keizer, Siemes, Claire, Jansman, Frank G. A., Kibbelaar, Robby E., Veeger, Nic J. G. M., Hoogendoorn, Mels, and van Roon, Eric N.
- Abstract
Purpose : Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D3 supplementation on PN. Methods: Thirty-nine MM patients with inadequate (< 75 nmol/L [= 30 ng/mL]) 25-hydroxyvitamin D (25(OH)D) levels were included in this multicenter, prospective, single-arm study, of whom 35 patients completed the study. They received oral vitamin D3 for 6 months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200 IU/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN. Results: Median 25(OH)D increased from 38 (IQR 32–52) nmol/L at baseline to 77 (IQR 72–87) nmol/L after 6 months (P < 0.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50–75 nmol/L. Furthermore, in 37% of the participants, PN severity decreased (P = 0.007). Conclusion: The use of substantially higher vitamin D3 doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research. [ABSTRACT FROM AUTHOR]
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- 2023
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121. No decrease in fracture risk despite 15 years of treatment evolution for multiple myeloma patients: A Danish nationwide case-control study.
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Oortgiesen, Berdien E., Driessen, Johanna H.M., Hoogendoorn, Mels, Kibbelaar, Robby E., Veeger, Nic J.G.M., van den Bergh, Joop P.W., Vestergaard, Peter, de Vries, Frank, and van Roon, Eric N.
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MULTIPLE myeloma , *VERTEBRAL fractures , *CASE-control method , *MONOCLONAL gammopathies , *TREATMENT effectiveness , *BONES - Abstract
While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time. To determine the effect of different treatment periods (1996–2000, 2001–2006 and 2007–2011) on the risk of fractures in patients with multiple myeloma. This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use. The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: OR adj [95% CI] 1996–2000: 1.7[1.3–2.3]; 2001–2006: 1.3[1.1–1.6]; 2007–2011: 1.7[1.4–2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: OR adj [95% CI] 1996–2000: 3.5[1.4–8.6]; 2001–2006: 4.0[1.9–8.2]; 2007–2011: 3.0[1.6–5.7]). Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions. • No decrease in fracture risk over time was found for multiple myeloma patients. • New treatment options do not guarantee a corresponding reduction in bone lesions. • There is a strong clinical need for new bone-sparing strategies in multiple myeloma. [ABSTRACT FROM AUTHOR]
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- 2020
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122. Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study.
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Saberi Hosnijeh, Fatemeh, van der Straten, Lina, Kater, Arnon P., van Oers, Marinus H.J., Posthuma, Ward F.M., Chamuleau, Martine E.D., Bellido, Mar, Doorduijn, Jeanette K., van Gelder, Michel, Hoogendoorn, Mels, de Boer, Fransien, te Raa, G. Doreen, Kerst, J. Martijn, Marijt, Erik W.A., Raymakers, Reinier A.P., Koene, Harry R., Schaafsma, Martijn R., Dobber, Johan A., Tonino, Sanne H., and Kersting, Sabina S.
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CHRONIC lymphocytic leukemia , *IMMUNOGLOBULIN heavy chains , *PROTEOMICS - Abstract
• The prognostic ability of IGHV mutational status and sex was validated in this cohort. • The markers sCD23, SPINT1, and LY9 have possible prognostic ability for EFS in CLL patients. • Patients with these marker levels above the median had a shorter EFS than those with marker levels below the median. • Unmutated IGHV patients with an sCD23 or sCD27 level above the median had the lowest EFS. Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients. [ABSTRACT FROM AUTHOR]
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- 2020
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123. New treatment opportunities for older patients with acute myeloid leukemia and the increasing importance of frailty assessment - An oncogeriatric perspective.
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Diekmann B, Timmerman M, Hempenius L, van Roon E, Franken B, and Hoogendoorn M
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- Humans, Azacitidine adverse effects, Quality of Life, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Sulfonamides adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Frailty epidemiology, Leukemia, Myeloid, Acute drug therapy
- Abstract
With the introduction of targeted chemotherapy drugs, a new age of treatment for acute myeloid leukemia (AML) has begun. The promotion of the azacitidine+venetoclax combination regimen to first line of treatment in patients deemed ineligible for intensive chemotherapy marks the first of many novel combination regimens becoming part of national treatment guidelines. We review recent phase II and III clinical trials and conclude that these novel regimens offer significant increases in response rates, remission rates, and overall survival. The incidence of adverse events, the accrued time toxicity, and the healthcare costs, however, are increasing as well. Compared with clinical trials, older patients in the real world frequently present with an inferior baseline health status, which is associated with an increased risk of experiencing side effects. The key to reaping the maximum benefit of the new agents and their combination regimens therefore lies in sufficient attention being given to a patients' preexisting comorbidities, potential frailty, and quality of life. A systematic collaboration between hemato-oncologists and geriatricians can be a potent first step towards addressing the increased treatment intensity patients with AML experience under the novel regimens. In this narrative review article we provide an overview of recent and ongoing clinical trials, highlight encountered adverse events, discuss frailty assessment options, and outline an oncogeriatic care path for older patients with AML., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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124. BCR::ABL1 kinase domain mutation testing and clinical outcome in a nationwide chronic myeloid leukemia patient population.
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Kockerols C, Valk PJM, Blijlevens NMA, Cornelissen JJ, Dinmohamed AG, Geelen I, Hoogendoorn M, Janssen JJWM, Daenen LGM, Reijden BAV, and Westerweel PE
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- Humans, Drug Resistance, Neoplasm genetics, Mutation, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
- Abstract
Objectives: Acquired missense mutations in the BCR::ABL1 kinase domain (KD) may cause tyrosine kinase inhibitor (TKI) treatment failure. Based on mutation-specific in vitro derived IC50-values, alternative TKI may be selected. We assessed clinical practice of BCR::ABL1 KD mutation testing, clinical response in relation to IC50-values, and clinical outcome of tested patients., Methods: Patients from six Dutch CML reference centers and a national registry were included once a mutational analysis was performed. Reasons for testing were categorized as suboptimal TKI response, and primary or secondary TKI resistance., Results: Four hundred twenty analyses were performed in 275 patients. Sixty-nine patients harbored at least one mutation. Most analyses were performed because of suboptimal TKI response but with low mutation incidence (4%), while most mutations were found in primary and secondary resistant patients (21% and 51%, respectively). Harboring a BCR::ABL1 mutation was associated with inferior overall survival (HR 3.2 [95% CI, 1.7-6.1; p < .001]). Clinically observed responses to TKI usually corresponded with the predicted TKI sensitivity based on the IC50-values, but a high IC50-value did not preclude a good clinical response per se., Conclusions: We recommend BCR::ABL1 KD mutation testing in particular in the context of primary or secondary resistance. IC50-values can direct the TKI choice for CML patients, but clinical efficacy can be seen despite adverse in vitro resistance., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2023
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125. Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL.
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van der Straten L, Stege CAM, Kersting S, Nasserinejad K, Dubois J, Dobber JA, Mellink CHM, van der Kevie-Kersemaekers AF, Evers LM, de Boer F, Koene HR, Schreurs J, van der Klift M, Velders GA, van der Spek E, van der Straaten HM, Hoogendoorn M, van Gelder M, Posthuma EFM, Visser HPJ, Houtenbos I, Idink CAM, Issa DE, Dompeling EC, van Zaanen HCT, Veelken JH, Levenga H, Tick LW, Terpstra WE, Tonino SH, Westerweel PE, Langerak AW, Kater AP, and Levin MD
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- Humans, Aged, Quality of Life, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Fatigue chemically induced, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis
- Abstract
Chronic lymphocytic leukemia (CLL)-related symptoms and morbidity related to the advanced age at diagnosis impairs the well-being of older adult patients. Therefore, it is essential to tailor treatment according to geriatric characteristics and aim for an improvement in health-related quality of life (HRQoL) as a primary treatment goal. In the HOVON139/GiVe trial, 12 cycles of fixed-duration venetoclax plus obinutuzumab (Ven-O) were shown to be effective and tolerable in FCR (fludarabine, cyclophosphamide, rituximab)-unfit patients with CLL (n = 67). However, prolonged venetoclax exposure as consolidation treatment led to increased toxicity with limited effect on minimal residual disease. To assess the impact of geriatric assessment on treatment outcomes and the patients' HRQoL, patient-reported outcomes (PROs), including function, depression, cognition, nutrition, physical performance, muscle parameters, comorbidities, and the European Organization for Research and Treatment of Cancer C30 and CLL17 questionnaires were assessed. At baseline, geriatric impairments were present in >90% of patients and ≥2 impairments present in 60% of patients predicted grade ≥3 nonhematological toxicity. During treatment, the number of geriatric impairments diminished significantly and clinically relevant improvements in HRQoL subscales were reached for global health status, physical functioning, role functioning, emotional functioning, fatigue, dyspnea, physical condition or fatigue, and worries or fears related to health and functioning. These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued. Collectively, frontline fixed-duration Ven-O improves overall PROs in older, unfit patients with CLL with and without geriatric impairments. This study was registered at EudraCT as 2015-004985-27 and the Netherlands Trial Register as NTR6043., (© 2023 by The American Society of Hematology.)
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- 2023
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126. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine.
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Hilberink JR, van Zeventer IA, Chitu DA, Pabst T, Klein SK, Stussi G, Griskevicius L, Valk PJM, Cloos J, van de Loosdrecht AA, Breems D, van Lammeren-Venema D, Boersma R, Jongen-Lavrencic M, Fehr M, Hoogendoorn M, Manz MG, Söhne M, van Marwijk Kooy R, Deeren D, van der Poel MWM, Legdeur MC, Tick L, Chalandon Y, Ammatuna E, Blum S, Löwenberg B, Ossenkoppele GJ, and Huls G
- Subjects
- Humans, Male, Female, Aged, Decitabine therapeutic use, Mutation, Treatment Outcome, Myelodysplastic Syndromes genetics, Leukemia, Myeloid, Acute genetics
- Abstract
Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival., (© 2023. The Author(s).)
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- 2023
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127. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
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Eichhorst B, Niemann CU, Kater AP, Fürstenau M, von Tresckow J, Zhang C, Robrecht S, Gregor M, Juliusson G, Thornton P, Staber PB, Tadmor T, Lindström V, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schöttker B, Nösslinger T, Janssens A, Christiansen I, Baumann M, Frederiksen H, van der Klift M, Jäger U, Leys MBL, Hoogendoorn M, Lotfi K, Hebart H, Gaska T, Koene H, Enggaard L, Goede J, Regelink JC, Widmer A, Simon F, De Silva N, Fink AM, Bahlo J, Fischer K, Wendtner CM, Kreuzer KA, Ritgen M, Brüggemann M, Tausch E, Levin MD, van Oers M, Geisler C, Stilgenbauer S, and Hallek M
- Subjects
- Humans, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Neoplasm, Residual diagnosis, Rituximab administration & dosage, Rituximab adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Background: Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking., Methods: In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10
-4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival., Results: A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%)., Conclusions: Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.)., (Copyright © 2023 Massachusetts Medical Society.)- Published
- 2023
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128. Treatment patterns in older patients with myelodysplastic syndromes: A population-based analysis reflecting the real world.
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Rozema J, Graafsma J, Hoogendoorn M, Kibbelaar R, Veeger N, and van Roon E
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- Humans, Male, Female, Aged, Lenalidomide, Treatment Outcome, Treatment Failure, Kaplan-Meier Estimate, Myelodysplastic Syndromes therapy
- Abstract
Introduction: Treatment for myelodysplastic syndromes (MDS) is complex, options are limited, and insight into consecutive treatments is lacking. We performed this study to assess the outcomes in a real-world cohort of patients with MDS., Materials and Methods: An observational population-based study was performed using the HemoBase registry. Treatment patterns and overall survival (OS) were analyzed with Kaplan-Meier analyses., Results: In 144 of 280 (51.4%) patients with MDS >50 years, first-line treatment was initiated. The median age was 75.1 years (range: 52.6-92.0); the majority were male (72.2%). Hypomethylating agents (HMA), intensive chemotherapy, lenalidomide, and erythropoiesis-stimulating agents (ESA) were given as first-line treatment to 31.1% (n = 45), 12.5% (n = 18), 2.8% (n = 4), and 53.5% (n = 77) of the population, respectively. The median treatment duration was 5.8 months (95% Confidence Interval [CI]: 1.1-10.4) for HMA, 1.7 months (95%CI: 0.9-2.6) for intensive chemotherapy, 10.8 months (95%CI: 4.7-17.0) for lenalidomide, and 14.8 months (95%CI: 11.4-18.1) for ESA. Consecutive treatments were given to 27.2% of patients. The main reasons for first-line treatment discontinuation were treatment failure (45.8%), toxicity (6.9%), or death (20.1%). Median OS after termination of the initial, second, and third treatment was 5.8 months (95%CI: 3.2-8.5), 9.3 months (95%CI: 0.0-19.6), and 1.0 months (95%CI: 0.0-5.1), respectively., Discussion: This study shows the treatment outcomes in a real-world population of older patients with MDS. Treatment duration and median OS after treatment discontinuation were relatively limited. There is still an urgent need for new treatment options, strategies to further optimize duration of existing treatments, and communication of realistic treatment goals and expectations, especially for older, higher-risk patients with MDS with a poor prognosis., Competing Interests: Declaration of Competing Interest All authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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129. Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial.
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Kersting S, Dubois J, Nasserinejad K, Dobber JA, Mellink C, van der Kevie-Kersemaekers AF, Evers LM, de Boer F, Koene HR, Schreurs J, van der Klift M, Velders GA, van der Spek E, van der Straaten HM, Hoogendoorn M, van Gelder M, Posthuma EFM, Visser HPJ, Houtenbos I, Idink CAM, Issa DE, Dompeling EC, van Zaanen HCT, Veelken H, Levenga H, Tick LW, Terpstra WE, Tonino SH, Boyer M, Mobasher M, Levin MD, and Kater AP
- Subjects
- Adolescent, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Female, Humans, Male, Sulfonamides, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Background: Fixed-duration 12 cycles of venetoclax plus obinutuzumab is established as first-line treatment for patients with chronic lymphocytic leukaemia. We aimed to determine the activity and safety of 12 cycles of venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated patients with chronic lymphocytic leukaemia who were unfit for fludarabine-based treatment, and whether this could be guided by minimal residual disease status., Methods: We conducted an open-label, randomised, parallel-group, phase 2 trial (HOVON 139/GiVe) at 25 hospitals in the Netherlands. Eligible patients were aged 18 years or older with previously untreated chronic lymphocytic leukaemia, had an ECOG performance status of 0-2, and were unfit for fludarabine-based treatment. All patients received two debulking cycles of intravenous obinutuzumab (100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8, 15, and day 1 of cycle two), followed by fixed-duration venetoclax plus obinutuzumab for 12 cycles (six cycles of intravenous obinutuzumab 1000 mg on day 1 and 12 during 28-day cycles of oral venetoclax, starting with a 5-week ramp-up and then 400 mg once daily until completion of cycle 12). Patients were then randomly assigned (1:1) by minimal residual disease status in peripheral blood, to receive either 12 cycles of venetoclax consolidation irrespective of minimal residual disease or venetoclax consolidation only if minimal residual disease was detected at randomisation. The primary endpoint was undetectable minimal residual disease in bone marrow and no progressive disease 3 months after end of consolidation treatment (or corresponding timepoint) by intention-to-treat. Safety was assessed in all patients who received at least one dose of any study drug. This is the primary endpoint analysis of this trial, which is ongoing and is registered with EudraCT (2015-004985-27)., Findings: Between Oct 28, 2016, and May 31, 2018, 70 patients were enrolled, of whom 67 (47 [70%] men and 20 [30%] women) received fixed-duration treatment and 62 were randomly assigned to receive 12 cycles of venetoclax consolidation (n=32) or minimal residual disease-guided venetoclax consolidation (n=30; one of whom was minimal residual disease positive at randomisation). Median follow-up was 35·2 months (IQR 31·5-41·3). 16 (50% [95% CI 32-68]) of 32 patients in the consolidation group and 16 (53% [34-72]) of 30 in the minimal residual disease-guided consolidation group met the primary endpoint of undetectable minimal residual disease in bone marrow and no progressive disease. 22 (69%) of 32 patients in the venetoclax consolidation group and 11 (37%) of 30 in the minimal residual disease-guided consolidation group had any adverse event (grade 2-4; mainly infections). The most common grade 3 or worse adverse events were infection (two [6%] of 32 patients in the consolidation group and one [3%] of 30 in the minimal residual disease-guided consolidation group) and neutropenia (two [6%] and two [7%]). There were no treatment-related deaths., Interpretation: Consolidation with venetoclax 12-cycle treatment increases the duration of known side-effects and does not prevent the loss of minimal residual disease response and subsequent risk of disease relapse., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests APK reports personal fees from AbbVie, LAVA, Genmab, Janssen, AstraZeneca, Roche/Genentech, and Bristol Myers Squibb; and research funding from AbbVie, Janssen, AstraZeneca, Roche/Genentech, and Bristol Myers Squibb. EvdS reports honoraria from Janssen and Amgen; and support for attending meetings from Janssen. JD reports research funding from Roche/Genentech. SK reports personal fees from Janssen, AbbVie, Novartis, Gilead, and Celgene; and research funding from AbbVie, Janssen, AstraZeneca, and Roche/Genentech. M-DL reports personal fees from AbbVie, Janssen, and Roche; and research funding from AbbVie, Janssen, AstraZeneca, and Roche/Genentech. SHT reports personal fees from Roche, Takeda, Incyte, Kite/Gilead, and Celgene. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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130. A clinical effect of disease-modifying treatment on alloimmunisation in transfused patients with myelodysplastic syndromes: data from a population-based study.
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Rozema J, Slim CL, Veeger NJGM, Kibbelaar RE, de Wit H, van Roon EN, and Hoogendoorn M
- Subjects
- Blood Transfusion, Humans, Incidence, Anemia, Hemolytic, Autoimmune, Blood Group Antigens, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes therapy
- Abstract
Background: Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS)., Materials and Methods: An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis., Results: 233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively., Discussion: In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.
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- 2022
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131. Improving the identification of frail elderly newly diagnosed multiple myeloma patients.
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Stege CAM, Nasserinejad K, Klein SK, Timmers GJ, Hoogendoorn M, Ypma PF, Nijhof IS, Velders GA, Strobbe L, Durdu-Rayman N, Westerman M, Davidis-van Schoonhoven MA, van Kampen RJW, Beeker A, Koster A, Dijk AC, van de Donk NWCJ, van der Spek E, Leys RBL, Silbermann MH, Groen K, van der Burg-de Graauw NCHP, Sinnige HAM, van der Hem KG, Levenga H, Bilgin YM, Sonneveld P, Levin MD, and Zweegman S
- Subjects
- Aged, Aged, 80 and over, Follow-Up Studies, Humans, Multiple Myeloma drug therapy, Multiple Myeloma pathology, Prognosis, Prospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Geriatric Assessment methods, Multiple Myeloma mortality
- Published
- 2021
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132. Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features.
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Aukema SM, Croci GA, Bens S, Oehl-Huber K, Wagener R, Ott G, Rosenwald A, Kluin PM, van den Berg E, Bosga-Bouwer AG, Hoogendoorn M, Hoster E, Bittmann I, Nagel I, Murga Penas EM, Kreuz M, Bausinger J, Belder W, Oschlies I, Dyer MJS, Jayne S, Siebert R, and Klapper W
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Child, Preschool, Clonal Evolution, Comparative Genomic Hybridization, Cytogenetic Analysis, DNA Nucleotidylexotransferase analysis, Diagnosis, Differential, Female, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Immunophenotyping, Lymphoma, Mantle-Cell immunology, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Neoplasm Grading, Phenotype, Predictive Value of Tests, Biomarkers, Tumor genetics, Chromosome Breakpoints, Cyclin D1 genetics, Gene Rearrangement, Lymphoma, Mantle-Cell genetics, Proto-Oncogene Proteins c-myc genetics
- Abstract
Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns. Thirteen out of fifteen MYC - R+ samples showed a non-classical cytology including pleomorphic (centroblastic, immunoblastic), anaplastic or blastoid. MYC translocation partners were IG-loci in 4/11 and non-IG loci in 7/11 analysed cases. The involved IG-loci included IGH in 3 cases and IGL in one case. PAX5 was the non-IG partner in 2/7 patients. The MYC - R+ MCL reported herein frequently displayed characteristics associated with an aggressive clinical course including high genomic-complexity (6/7 samples), frequent deletions involving the CDKN2A locus (7/10 samples), high Ki-67 proliferation index (12/13 samples) and frequent P53 expression (13/13 samples). Of note, in 4/14 samples, SOX11 was not or only focally expressed and 3/13 samples showed focal or diffuse TdT-positivity presenting a diagnostic challenge as these features could point to a differential diagnosis of diffuse large B-cell lymphoma and/or lymphoblastic lymphoma/leukaemia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)
- Published
- 2021
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133. Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes: a population-based study.
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Rozema J, Hoogendoorn M, Kibbelaar R, van den Berg E, Veeger N, and van Roon E
- Subjects
- Aged, Comorbidity, Female, Humans, Proportional Hazards Models, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes therapy, Neoplasms, Neoplasms, Second Primary diagnosis, Neoplasms, Second Primary epidemiology
- Abstract
Population-based studies that contain detailed clinical data on patients with myelodysplastic syndrome (MDS) are scarce. This study focused on the real-world overall survival (OS) of MDS patients in association with comorbidities, specifically malignancies. An observational population-based study using the HemoBase registry was performed, including all patients with MDS diagnosed between 2005 and 2017 in Friesland, a Dutch province. Detailed information about diagnosis, patient characteristics, previous treatment of malignancies, and comorbidities according to the Charlson Comorbidity Index (CCI) was collected from electronic health records. Patients were followed up until June 2019. Kaplan-Meier plots and Cox regression analyses were used to study survival differences. In the 291 patients diagnosed with MDS, the median OS was 25.3 months (95% confidence interval [CI], 20.3-30.2). OS was significantly better for patients with CCI score <4, age <65 years, female sex, and low-risk MDS. Fifty-seven patients (20%) had encountered a prior malignancy (excluding nonmelanoma skin cancer), and a majority (38 patients; 67%) were therapy related. Both therapy-related and secondary MDSs were associated with worse OS (hazard ratio, 1.51; 95% CI, 1.02-2.23 and 1.58; 95% CI, 0.95-2.65, respectively), as compared with de novo MDS patients (P = .04). Patients in remission at time of MDS diagnosis had a similar median OS compared with patients with de novo MDS (25.5 vs 28.3 months). This population-based study involving all newly diagnosed MDS patients over a 13-year period in Friesland showed that multiple comorbidities, including previous malignancies, are associated with shorter OS. OS was not related to the use of radiotherapy or chemotherapy., (© 2021 by The American Society of Hematology.)
- Published
- 2021
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134. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial.
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Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, and Ossenkoppele GJ
- Subjects
- Adolescent, Adult, Aged, Humans, Lenalidomide, Middle Aged, Remission Induction, Transplantation, Autologous, Young Adult, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy
- Abstract
Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study., (© 2021 by The American Society of Hematology.)
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- 2021
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135. Rituximab-PECC induction followed by 90 Y-ibritumomab tiuxetan consolidation in relapsed or refractory DLBCL patients who are ineligible for or have failed ASCT: results from a phase II HOVON study.
- Author
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Lugtenburg PJ, Zijlstra JM, Doorduijn JK, Böhmer LH, Hoogendoorn M, Berenschot HW, Beeker A, van der Burg-de Graauw NC, Schouten HC, Bilgin YM, Kersten MJ, Koene HR, Herbers AHE, de Jong D, Hijmering N, Lam KH, Chiţu D, Brouwer RE, and van Imhoff GW
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Autografts, Carmustine administration & dosage, Carmustine adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Humans, Male, Middle Aged, Prednisone administration & dosage, Prednisone adverse effects, Rituximab adverse effects, Survival Rate, Vindesine administration & dosage, Vindesine adverse effects, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, Large B-Cell, Diffuse mortality, Lymphoma, Large B-Cell, Diffuse therapy, Rituximab administration & dosage, Stem Cell Transplantation
- Abstract
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with
90 Y-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade ≥3 adverse events from start of90 Y-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to90 Y-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after90 Y-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of90 Y-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and90 Y-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with90 Y-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2019
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136. Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment.
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de Weerdt I, Hofland T, de Boer R, Dobber JA, Dubois J, van Nieuwenhuize D, Mobasher M, de Boer F, Hoogendoorn M, Velders GA, van der Klift M, Remmerswaal EBM, Bemelman FJ, Niemann CU, Kersting S, Levin MD, Eldering E, Tonino SH, and Kater AP
- Subjects
- Adult, Aged, Antineoplastic Agents immunology, Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, CD8-Positive T-Lymphocytes, Female, Humans, Immunosuppression Therapy, Killer Cells, Natural, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Male, Middle Aged, Sulfonamides pharmacology, Sulfonamides therapeutic use, T-Lymphocytes, Regulatory, Blood immunology, Bridged Bicyclo Compounds, Heterocyclic immunology, Immune System drug effects, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Lymph Nodes immunology, Lymphocytes drug effects, Sulfonamides immunology
- Abstract
Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (T
regs ) and CLL supportive follicular T helper (Tfh ) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg , and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells., (© 2019 by The American Society of Hematology.)- Published
- 2019
- Full Text
- View/download PDF
137. [Proton pump inhibitors when using clopidogrel: balance between necessity and disadvantages].
- Author
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van der Elst K, Oortgiesen B, Kruik-Kollöffel W, Hoogendoorn M, Hofma S, and van Roon E
- Subjects
- Aspirin adverse effects, Clopidogrel administration & dosage, Drug Interactions, Female, Gastrointestinal Diseases, Gastrointestinal Hemorrhage chemically induced, Humans, Male, Peptic Ulcer chemically induced, Platelet Aggregation Inhibitors adverse effects, Proton Pump Inhibitors administration & dosage, Risk Factors, Clopidogrel adverse effects, Gastrointestinal Hemorrhage prevention & control, Peptic Ulcer prevention & control, Proton Pump Inhibitors adverse effects
- Abstract
Rationale When patients are using carbasalate calcium or acetylsalicylic acid (ASA), it is recommended to prescribe a proton pump inhibitor (PPI) in order to prevent gastrointestinal (GI) bleeding. Should this recommendation also be followed for patients who are using clopidogrel in monotherapy, which is increasingly the case in practice? Method In a systematic literature review of the occurrence of GI bleeding when using clopidogrel versus ASA, we included 9 studies that compared the risk of GI bleeding when using ASA with clopidogrel monotherapy. Results These 9 studies on clopidogrel and ASA show that the risk of GI bleeding is also elevated when using clopidogrel monotherapy and that it is comparable with the risk of GI bleeding when using ASA. Conclusion Based on the current literature, we recommend prescribing pantoprazole to patients who are using clopidogrel monotherapy and have additional risk factors for GI bleeding, in accordance with the procedure for low-dose ASA. The risk of GI bleeding must be weighed against the disadvantages of using PPIs.
- Published
- 2019
138. Feasibility and efficacy of addition of individualized-dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia.
- Author
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Kater AP, van Oers MHJ, van Norden Y, van der Straten L, Driessen J, Posthuma WFM, Schipperus M, Chamuleau MED, Nijland M, Doorduijn JK, Van Gelder M, Hoogendoorn M, De Croon F, Wittebol S, Kerst JM, Marijt EWA, Raymakers RAP, Schaafsma MR, Dobber JA, Kersting S, and Levin MD
- Subjects
- Adolescent, Adult, Chlorambucil administration & dosage, Disease-Free Survival, Feasibility Studies, Female, Humans, Lenalidomide administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Rituximab administration & dosage, Survival Rate, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m
2 daily), rituximab (375 mg/m2 cycle 1 and 500 mg/m2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34 ., (Copyright© 2019 Ferrata Storti Foundation.)- Published
- 2019
- Full Text
- View/download PDF
139. Validation of the EUTOS long-term survival score in a recent independent cohort of "real world" CML patients.
- Author
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Geelen IGP, Sandin F, Thielen N, Janssen JJWM, Hoogendoorn M, Visser O, Cornelissen JJ, Hoglund M, and Westerweel PE
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Middle Aged, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
- Published
- 2018
- Full Text
- View/download PDF
140. Clinical challenges related to novel oral anticoagulants: drug-drug interactions and monitoring.
- Author
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Altena R, van Roon E, Folkeringa R, de Wit H, and Hoogendoorn M
- Subjects
- Aged, Drug Incompatibility, Female, Humans, Morpholines administration & dosage, Morpholines adverse effects, Morpholines pharmacokinetics, Rivaroxaban, Thiophenes administration & dosage, Thiophenes adverse effects, Thiophenes pharmacokinetics, Antibiotics, Antitubercular administration & dosage, Antibiotics, Antitubercular adverse effects, Antibiotics, Antitubercular pharmacokinetics, Anticoagulants administration & dosage, Anticoagulants adverse effects, Anticoagulants pharmacokinetics, Atrial Fibrillation therapy, Ciprofloxacin administration & dosage, Ciprofloxacin adverse effects, Ciprofloxacin pharmacokinetics, Coronary Artery Bypass, Rifampin administration & dosage, Rifampin adverse effects, Rifampin pharmacokinetics
- Published
- 2014
- Full Text
- View/download PDF
141. [An immunocompromised patient with a histoplasmosis infection: a weakened patient's undisclosed trip].
- Author
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de Borst MH, van Zeijl JH, Grond J, and Hoogendoorn M
- Subjects
- Aged, Antifungal Agents therapeutic use, Fatal Outcome, Histoplasmosis drug therapy, Histoplasmosis immunology, Histoplasmosis microbiology, Humans, Itraconazole therapeutic use, Male, Histoplasmosis diagnosis, Immunocompromised Host, Travel
- Abstract
A 69-year-old man with chronic lymphocytic leukemia presented with fever and a productive cough. He was diagnosed with a histoplasmosis infection, caused by the dimorphic fungus Histoplasma capsulatum, which is rare in the Netherlands but endemic in parts of the United States and South America. The patient was treated with high doses of itraconazole and gamma globulin infusions. This initially led to a clinical improvement, but eventually he developed a probable progressive histoplasmosis. The patient refused additional treatment and died. In immunocompromised patients, infections of the respiratory tract can be caused by a broad variety of agents. Knowledge of the patient's travel history is crucial to determine or exclude certain causal agents.
- Published
- 2010
142. Early detection and rapid isolation of leukemia-reactive donor T cells for adoptive transfer using the IFN-gamma secretion assay.
- Author
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Jedema I, Meij P, Steeneveld E, Hoogendoorn M, Nijmeijer BA, van de Meent M, van Luxemburg-Heijs SA, Willemze R, and Falkenburg JH
- Subjects
- Cell Survival, HLA Antigens metabolism, Humans, Immunophenotyping, Immunotherapy, Adoptive instrumentation, Leukemia metabolism, Leukemia, B-Cell pathology, Leukemia, B-Cell therapy, Leukemia, Myeloid pathology, Leukemia, Myeloid therapy, Monocytes metabolism, Stem Cell Transplantation methods, T-Lymphocytes metabolism, Transplantation, Homologous, Adoptive Transfer, Immunotherapy, Adoptive methods, Interferon-gamma metabolism, T-Lymphocytes cytology
- Abstract
Purpose: The poor immunogenicity of most leukemias and the lack of specificity of the donor T cells limit the in vivo effectiveness of conventional donor lymphocyte infusions in many patients suffering from persistent or recurrent leukemia after allogeneic stem cell transplantation. These limitations may be overcome by the adoptive transfer of in vitro generated leukemia-reactive T cells. Although the potential clinical efficacy of this approach has been shown previously, lack of reproducibility of the procedure and the inability to show persistence and survival of the transferred T cells hampered further clinical application. The purpose of this study was to develop a new, broadly applicable strategy for the efficient generation and isolation of leukemia-reactive T cells with a better probability to survive and expand in vivo., Experimental Design: Myeloid and B-cell leukemias were modified into professional immunogenic antigen-presenting cells, and used to stimulate HLA-matched donor T cells. After two stimulations, responding donor T cells were isolated based on their secretion of IFN-gamma and tested for their capacity to recognize and kill the primary leukemia., Results: Using one universal stimulation and isolation protocol for various forms of leukemia, T-cell populations containing high frequencies of leukemia-reactive T cells could reproducibly be generated and early isolated under mild stimulatory conditions. Isolated T cells still had high proliferative potential and their reactivity seemed to be restricted to cells of the patient's hematopoiesis., Conclusion: We here show a new robust procedure for the generation and isolation of leukemia-reactive T cells for adoptive transfer.
- Published
- 2007
- Full Text
- View/download PDF
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