33 results on '"Hoogendoorn, Mels"'
Search Results
2. 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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3. BCR::ABL1 kinase domain mutation testing and clinical outcome in a nationwide chronic myeloid leukemia patient population.
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Kockerols, Camille, Valk, Peter J. M., Blijlevens, Nicole M. A., Cornelissen, Jan J., Dinmohamed, Avinash G., Geelen, Inge, Hoogendoorn, Mels, Janssen, Jeroen J. W. M., Daenen, Laura G. M., Reijden, Bert A. van der, and Westerweel, Peter E.
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CHRONIC myeloid leukemia , *GENETIC mutation , *CHRONIC leukemia , *PROTEIN-tyrosine kinase inhibitors , *MISSENSE mutation , *TREATMENT failure - 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. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Primary Epstein-Barr virus infection diffusing F18-fluorodeoxyglucose-positron emission tomography/computed tomography response monitoring of Hodgkin's disease: a case report.
- Author
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Balink, Hans and Hoogendoorn, Mels
- 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 chemotherapy-refractory 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]- Published
- 2014
- Full Text
- View/download PDF
5. 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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6. Adherence to quality indicators in chronic myeloid leukemia care: results from a population-based study in The Netherlands.
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Ector, Geneviève I.C.G., Geelen, Inge G. P., Dinmohamed, Avinash G., Hoogendoorn, Mels, Westerweel, Peter E., Hermens, Rosella P.M.G., and Blijlevens, Nicole M.A.
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CHRONIC myeloid leukemia , *CHRONIC leukemia , *SHOWROOMS , *OVERALL survival , *SURVIVAL rate , *LEUKEMIA - Abstract
Suboptimal guideline adherence in chronic myeloid leukemia (CML) care is associated with worse treatment outcomes. Current study focused on adherence to seven quality indicators (QIs) based on the European Leukemia Network guideline (one diagnostic, one therapeutic, and five monitoring indicators). Data were obtained from population-based registries in the Netherlands of 405 newly diagnosed chronic phase CML patients between January 2008 and April 2013. Compliance rates regarding diagnostic and therapeutic indicator were 83% and 78%, respectively. Monitoring indicators rates were lower: 21–27% for indicators concerning the first year and 58% and 62% for the second and third year, respectively. Noncompliance occurred mostly due to non-timely monitoring. Twenty cases did not comply with any indicator, 6% complied with all indicators. After adjustment for age, overall survival rates did not differ significantly between the groups. Adherence to guideline-based QIs was suboptimal. This demonstrates the evidence-practice gap, shows room for improvement and underscores the need for real-world data. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes.
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Rozema, Johanne, van Asten, Ivar, Kwant, Beau, Kibbelaar, Robby E., Veeger, Nic J. G. M., de Wit, Harry, van Roon, Eric N., and Hoogendoorn, Mels
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CHELATION therapy , *MYELODYSPLASTIC syndromes , *FERRITIN , *IRON , *MEDICAL records - Abstract
Objectives: In patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 μg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice. Methods: We performed an observational population‐based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower‐risk MDS was collected from health records. Results: Two hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p =.016). Clinical performance was also associated with initiating ICT (RR: 5.99, p <.001). ICT was offered to 22.3% (n = 25) of eligible patients. Conclusions: In this population‐based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Management of infection prophylaxis in Dutch patients with myelodysplastic syndromes, a web‐based case vignette questionnaire: The MINDSET study.
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Rozema, Johanne, van Roon, Eric, Vogelzang, Lars, Kibbelaar, Robby, Veeger, Nic, van de Loosdrecht, Arjan, and Hoogendoorn, Mels
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MYELODYSPLASTIC syndromes , *ANTIFUNGAL agents , *VIGNETTES , *PREVENTIVE medicine , *INFECTION prevention - Abstract
Objectives: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). The objective of the MINDSET study was to evaluate haematologists' management of infection prevention in MDS patients using a case vignette study and to assess the availability of guidelines. Methods: We conducted a web‐based, nationwide survey amongst haematologists in the Netherlands between September and December 2021. The survey included a set of case vignettes. In addition, the availability of protocols was evaluated. Results: Sixty responses were obtained (23.6%). These responses were well distributed across hospital types as well as level of experience. No protocols regarding infection prophylaxis specifically for MDS patients were received. In the case vignette of a 75‐year‐old MDS patient, respondents would primarily prescribe infection prophylaxis in case of recurrent infections (96.7%) and neutropenia (75.0% for absolute neutrophil count [ANC] < 0.2 × 109/L and 53.3% for ANC < 0.5 × 109/L), especially in combination with hypomethylating agents (80.0%), lenalidomide (66.7%) or chemotherapy (51.7%). Respondents would predominantly choose antibacterial agents (85.0%), followed by antifungal agents (71.7%). Conclusions: This study showed diverse reasons and considerations of haematologists regarding whether to prescribe infection prophylaxis in MDS patients. Given the seriousness of infections in MDS patients, patient‐tailored recommendations might be valuable in clinical decision‐making. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients.
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Waal, Esther G. M., Munck, Linda, Hoogendoorn, Mels, Woolthuis, Gerhard, Velden, Annette, Tromp, Yvonne, Vellenga, Edo, and Hovenga, Sjoerd
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COMBINATION drug therapy , *MULTIPLE myeloma treatment , *CYCLOPHOSPHAMIDE , *BORTEZOMIB , *DEXAMETHASONE , *DISEASE relapse , *THERAPEUTICS - Abstract
Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow- up was 27.1 (0.46-54.4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18.4 months (range 0.13-43.5) and the median OS was 28.1 months (range 0.13-54.4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Serial ADAMTS13 measurements during initial plasma exchange therapy guide decisions for management of unresponsive thrombotic thrombocytopenic purpura.
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van der Veen, Betty S., Besseling, Rens, and Hoogendoorn, Mels
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THROMBOTIC thrombocytopenic purpura treatment , *PLASMA exchange (Therapeutics) , *DISINTEGRINS , *METALLOPROTEINASES , *THROMBOSPONDIN-1 , *MEDICAL decision making , *ANTICOAGULANTS , *DECISION making , *GLYCOPROTEINS , *HEPARIN , *THROMBOTIC thrombocytopenic purpura - Abstract
Background: The standard therapy in acquired thrombotic thrombocytopenic purpura (TTP) is plasma exchange. In unresponsive TTP, intensification of plasma exchange and immunomodulatory therapy can be initiated but it can be complicated to select for patients that will benefit from intensification.Case Report: We describe two cases of newly diagnosed TTP with a complicated clinical course during initial treatment with plasma exchange. In one case, after an initial response to plasma exchange, a decrease in platelet count was observed on Day 7. The normalized ADAMTS13 activity guided the clinicians in the diagnosis of a concurrent heparin-induced thrombocytopenia due to the heparin lock, used for the indwelling catheter. The other case with TTP clinically deteriorated early during initial treatment. Reevaluation on Day 5, including ADAMTS13 activity, which was undetectably low, supported the clinical decision to intensify the plasma exchange to twice daily and start with the immunomodulating agent rituximab. In both clinically complicated cases measurements of ADAMTS13 activity during plasma exchange proved to be useful in guiding treatment decisions.Conclusion: Serial measurements of ADAMTS13 activity should be considered in patients with newly diagnosed TTP with an unpredictable clinical course during initial therapeutic plasma exchange. These measurements may provide pivotal clinical insights on appropriate patient management. [ABSTRACT FROM AUTHOR]- Published
- 2015
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11. Comorbidity is an independent prognostic factor in patients with advanced-stage diffuse large B-cell lymphoma treated with R- CHOP: a population-based cohort study.
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Wieringa, Andre, Boslooper, Karin, Hoogendoorn, Mels, Joosten, Peter, Beerden, Tim, Storm, Huib, Kibbelaar, Robby E., Veldhuis, Gerrit J., Kamp, Harmen, Rees, Bastiaan, Kluin ‐ Nelemans, Hanneke C., Veeger, Nic J. G. M., and Roon, Eric N.
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COHORT analysis , *COMORBIDITY , *B cell lymphoma , *PROGNOSIS , *CELL populations , *DOXORUBICIN , *CYCLOPHOSPHAMIDE , *PATIENTS - Abstract
An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma ( DLBCL) treated with R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index ( CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R- CHOP schedule was completed by 84% and 75% reached complete remission ( CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival ( OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/ IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R- CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities. [ABSTRACT FROM AUTHOR]
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- 2014
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12. Patterns of transfusion burden in an unselected population of patients with myelodysplastic syndromes: A population‐based study.
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Rozema, Johanne, van Roon, Eric N., Kibbelaar, Robby E., Veeger, Nic J. G. M., Slim, Christiaan L., de Wit, Harry, and Hoogendoorn, Mels
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MYELODYSPLASTIC syndromes , *FETOFETAL transfusion , *ELECTRONIC health records , *TREATMENT effectiveness , *REGRESSION analysis , *ODDS ratio - Abstract
Background: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real‐world MDS population is largely unknown. Study design and methods: An observational, retrospective, population‐based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed. Results: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3–7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75–84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84–8.82), high‐risk MDS patients (OR 2.88, 95% CI: 1.08–7.68) and MDS‐EB‐2 patients (OR 7.07, 95% CI: 2.17–22.90) were particularly at risk for a HTB. Discussion This study provides a reliable estimate of the transfusion burden in real‐world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low‐ and high‐risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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13. 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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14. Bortezomib maintenance after R‐CHOP, cytarabine and autologous stem cell transplantation in newly diagnosed patients with mantle cell lymphoma, results of a randomised phase II HOVON trial.
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Doorduijn, Jeanette K., Zijlstra, Josee M., Lugtenburg, Pieternella J., Kersten, Marie Josee, Böhmer, Lara H., Minnema, Monique C., MacKenzie, Marius A., van Marwijk Kooij, Rien, Jongh, Eva, Snijders, Tjeerd J.F., Weerdt, Okke, Gelder, Michel, Hoogendoorn, Mels, Leys, Rineke B.L., Kibbelaar, Robby E., Jong, Daphne, Chitu, Dana A., Van't Veer, Mars B., and Kluin‐Nelemans, Hanneke C.
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MANTLE cell lymphoma , *STEM cell transplantation , *BORTEZOMIB - Abstract
Rituximab‐containing induction followed by autologous stem cell transplantation (ASCT) is the standard first‐line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo‐immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high‐dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow‐up of 77·5 months for patients still alive, 5‐year event‐free survival (EFS) was 51% (95% CI 42–59%); 5‐year overall survival (OS) was 73% (95% CI 65–80%). The median follow‐up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5‐year EFS of 63% (95% CI 44–78%) and 5‐year OS of 90% (95% CI 72–97%). The patients randomised to observation had 5‐year PFS of 60% (95% CI, 40–75%) and OS of 90% (95% CI 72–97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT. [ABSTRACT FROM AUTHOR]
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- 2020
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15. Native aortic valve endocarditis with Morganella morganii in a patient with multiple myeloma and valvular amyloidosis: a case report.
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van Bentum, Renée, Nieken, Judith, de Waal, Esther, and Hoogendoorn, Mels
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AORTIC valve , *INFECTIVE endocarditis , *CARDIAC amyloidosis , *MULTIPLE myeloma , *AMYLOIDOSIS , *ENDOCARDITIS , *AORTIC valve insufficiency - Abstract
Background: Patients with multiple myeloma (MM) are known to be immune incompetent and experience higher incidences of infectious diseases. However, infective endocarditis (IE) is rarely observed in patients with MM and Morganella morganii (M. morganii) has rarely been associated with IE.Case Presentation: A 72-year-old female receiving 4th line treatment for MM presented with fever and concomitant confusion. Urinary culture revealed growth of Escherichia coli, wherefore broadspectrum penicillin and high-dose corticosteroids were initiated. However, blood cultures showed growth of M. morganii. Fluoroquinolone was added due to penicillin-resistance of the Morganella species. Two days after admission, the patient acutely deteriorated with hemodynamic instability. Gentamicin and high dose corticosteroids were added. Echocardiography showed marked aortic valve vegetation with severe aortic valve regurgitation, leading to the diagnosis of bacterial endocarditis of the native aortic valve. Shortly after diagnosis, the patient died. At autopsy, vegetation with gram-negative rods in the native aortic valve was observed, confirming the diagnosis of M. morganii-endocarditis. Additional staining for amyloid confirmed advanced light-chain (AL) amyloidosis with extensive amyloid depositions of the aortic valve and valvular damage as complications of her MM.Conclusions: Our case suggests that IE with M. morganii was facilitated by the combination of the cardiac amyloidosis with valvular impairment and the profound immune deficiency caused by the several chemo-immunomodulatory treatment lines and the MM itself. This case further illustrates that awareness for rare opportunistic infections in an era with growing potential of combined chemoimmunotherapy is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2019
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16. Rituximab‐PECC induction followed by 90Y‐ibritumomab tiuxetan consolidation in relapsed or refractory DLBCL patients who are ineligible for or have failed ASCT: results from a phase II HOVON study.
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Lugtenburg, Pieternella J., Zijlstra, Josee M., Doorduijn, Jeanette K., Böhmer, Lara H., Hoogendoorn, Mels, Berenschot, Henriette W., Beeker, Aart, van der Burg‐de Graauw, Nicole C., Schouten, Harry C., Bilgin, Yavuz M., Kersten, Marie‐Jose, Koene, Harry R., Herbers, Alexandra H. E., de Jong, Daphne, Hijmering, Nathalie, Lam, King H., Chiţu, Dana, Brouwer, Rolf E., and van Imhoff, Gustaaf W.
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STEM cell transplantation - Abstract
Summary: 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 90Y‐ibritumomab tiuxetan in responsive patients. Primary endpoints were failure‐free survival (FFS) and incidence of grade ≥3 adverse events from start of 90Y‐ibritumomab tiuxetan. The overall response rate after R‐PECC was 50%. Twenty‐nine of 31 responsive patients proceeded to 90Y‐ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90Y‐ibritumomab tiuxetan. One‐year FFS and overall survival (OS) from start of 90Y‐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 and 90Y‐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 with 90Y‐ibritumomab tiuxetan resulted in long‐term response durations in approximately one third of the patients that received it. [ABSTRACT FROM AUTHOR]
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- 2019
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17. Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.
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Geelen, Inge G. P., Thielen, Noortje, Janssen, Jeroen J. W. M., Hoogendoorn, Mels, Roosma, Tanja J. A., Valk, Peter J. M., Visser, Otto, Cornelissen, Jan J., and Westerweel, Peter E.
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TREATMENT of chronic myeloid leukemia , *HUMAN cytogenetics , *CHROMOSOME abnormalities , *BONE marrow , *MOLECULAR diagnosis , *CHRONIC myeloid leukemia , *PREVENTION ,PREVENTION of disease progression - Abstract
Abstract: Objectives: The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. Methods: In a population‐based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. Results: The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular “warning.” The development of additional cytogenetic abnormalities was always accompanied with molecular failure. Conclusion: We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re‐assessment should still be performed when molecular response is suboptimal. [ABSTRACT FROM AUTHOR]
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- 2018
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18. MYC expression and translocation analyses in low-grade and transformed follicular lymphoma.
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Aukema, Sietse M, Pel, Roel, Nagel, Inga, Bens, Susanne, Siebert, Reiner, Rosati, Stefano, Berg, Eva, Bosga‐Bouwer, Anneke G, Kibbelaar, Robby E, Hoogendoorn, Mels, Imhoff, Gustaaf W, Kluin‐Nelemans, Hanneke C, Kluin, Philip M, and Nijland, Marcel
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LYMPHOMAS , *MYC oncogenes , *CHROMOSOMAL translocation , *IMMUNOHISTOCHEMISTRY , *IMMUNOGLOBULINS , *FLUORESCENCE in situ hybridization , *BCL-2 genes , *GENE expression , *GENETICS - Abstract
Aims Low-grade follicular lymphoma ( FL) (grade 1/2, FL1/2) has an annual risk of transformation of ≈3%, which is associated with aberrations in CDKN2A/ B, TP53, and MYC. As in diffuse large B-cell lymphoma, high MYC expression in transformed FL ( tFL) might predict a MYC breakpoint. Methods and results We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in four isolated biopsies of tFL. As controls, 28 biopsies of FL1/2 without transformation (median follow-up of 105 months) and nine biopsies of FL3A/B were analysed. In the 20 FL1/2- tFL pairs, MYC expression was significantly higher in tFL than in the initial FL1/2 biopsies (median 54% versus 6%; 7% in FL3A, and 35% in FL3B). MYC breaks ( MYC-R) were detected in eight of 21 (38%) tFLs analysed by fluorescence in-situ hybridization ( FISH), with a median MYC score of 86%. In two of the analysed tFL cases, the translocation was already detected in antecedent FL1/2. MYC partners were immunoglobulin ( IG) loci in three of eight cases (one IGL, one IGH, and one IGK) and non- IG in five of eight cases (two PAX5, one BCL6, and two unknown). Of the eight MYC-R+ cases, six were BCL2+/ MYC+ double-hit, one was BCL2+/ BCL6+/ MYC+ triple-hit, and one was MYC+ single-hit. All three IG- MYC+ cases showed a MYC expression level of >85%, whereas the five cases with a non- IG MYC partner had a wider range of expression (median 68%, range 13-86%). Among the 13 MYC-R− tFLs, two groups with almost dichotomous MYC expression could be observed (three cases showed ≥90% MYC expression), suggesting alternative mechanisms of MYC activation. Conclusions we show an increase in MYC expression from FL1/2 to tFL. MYC breakpoints were present in ≈40% of the cases, which is markedly higher than in de novo DLBCL. MYC expression was uniformly high in cases with an IG- MYC translocation but much more heterogeneous and in part independent of the presence of a MYC break in non- IG- MYC and MYC-negative cases. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
19. 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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20. Restoration of renal function in patients with newly diagnosed multiple myeloma is not associated with improved survival: a population-based study.
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de Vries, Joost C., Oortgiesen, Berdien, Hemmelder, Marc H., van Roon, Eric, Kibbelaar, Robby E., Veeger, Nic, and Hoogendoorn, Mels
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MULTIPLE myeloma , *CHRONIC kidney failure , *SURVIVAL , *THALIDOMIDE , *BORTEZOMIB , *PATIENTS , *PROGNOSIS - Abstract
Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1.08, 95% CI = 0.67–1.74,p = .76). In multivariable analysis, baseline eGFR <30 ml/min (HR = 1.71), age >70 yrs (HR = 1.77), hypercalcemia (HR = 2.73), lambda Bence–Jones (HR= 1.76), and initial treatment regimen (HR = 0.89 for thalidomide, HR = 1.95 in treatment regimens without novel agents and HR = 3.60 for no chemotherapy, all vs. bortezomib) were associated with decreased OS. In conclusion, achieving renal response was not associated with improved OS. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
21. Fatal Cobalt Toxicity after a Non-Metal-on-Metal Total Hip Arthroplasty.
- Author
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Peters, Rinne M., Willemse, Pax, Rijk, Paul C., Hoogendoorn, Mels, and Zijlstra, Wierd P.
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COBALT , *TOTAL hip replacement , *TOXICITY testing , *X-rays , *FEMUR head - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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22. Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission.
- Author
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Versluis, Jurjen, Kalin, Burak, Zeijlemaker, Wendelien, Passweg, Jakob, Graux, Carlos, Manz, Markus G., Vekemans, Marie-Christiane, Biemond, Bart J., Legdeur, Marie-Cecile J.C., Kooy, Marinus van Marwijk, de Weerdt, Okke, Wijermans, Pierre W., Hoogendoorn, Mels, Bargetzi, Mario J., Kuball, Juergen, Schouten, Harry C., van der Velden, Vincent H.J., Janssen, Jeroen J.W.M., Pabst, Thomas, and Lowenberg, Bob
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- *
ACUTE myeloid leukemia , *HEMATOPOIETIC stem cell transplantation , *CANCER remission , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Purpose: The detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) may improve future risk-adapted treatment strategies. We assessed whether MRD-positive and MRD-negative patients with AML benefit differently from the graft-versus-leukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT). Methods: A total of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research AML trials, of whom 547 obtained a first complete remission, received postremission treatment (PRT), and had available flow cytometric MRD before PRT. MRD positivity was defined as more than 0.1% cells with a leukemia-associated immunophenotype within the WBC compartment. PRT consisted of alloHSCT (n = 282), conventional PRT by a third cycle of chemotherapy (n = 160), or autologous hematopoietic stem-cell transplantation (n = 105). Results: MRD was positive in 129 patients (24%) after induction chemotherapy before proceeding to PRT. Overall survival and relapse-free survival were significantly better in patients without MRD before PRT compared with MRD-positive patients (65% ± 2% v 50% ± 5% at 4 years; P =.002; and 58% ± 3% v 38% ± 4%; P <.001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% ± 2% compared with 54% ± 4%; P <.001, respectively). Multivariable analysis with adjustment for covariables showed that the incidence of relapse was significantly reduced after alloHSCT compared with chemotherapy or autologous hematopoietic stem cell transplantation (hazard ratio [HR], 0.36; P <.001), which was similarly exerted in both MRD-negative and MRD-positive patients (HR, 0.38; P <.001; and HR, 0.35; P <.001, respectively). Conclusion: The graft-versus-leukemia effect of alloHSCT is equally present in MRD-positive and MRD-negative patients, which advocates a personalized application of alloHSCT, taking into account the risk of relapse determined by AML risk group and MRD status, as well as the counterbalancing risk of nonrelapse mortality. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
23. New insights in the neurological phenotype of aceruloplasminemia in Caucasian patients.
- Author
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Vroegindeweij, Lena H.P., Langendonk, Janneke G., Langeveld, Mirjam, Hoogendoorn, Mels, Kievit, Anneke J.A., Di Raimondo, Domenico, Wilson, J.H. Paul, and Boon, Agnita J.W.
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MOVEMENT disorders , *NEUROLOGY , *PHENOTYPES , *CAUCASIAN race , *COGNITION , *SEVERITY of illness index , *YOUTH mortality , *DISEASES , *BLOOD proteins , *GENEALOGY , *GENETIC techniques , *GLOBULINS , *IRON metabolism disorders , *LONGITUDINAL method , *NEURODEGENERATION , *NEUROLOGICAL disorders , *WHITE people - Abstract
Introduction: The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This 'classical' phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients.Methods: Data on neurological presentation and follow-up were gathered from both our patients, homozygous for the G631R mutation in the CP gene, and other published Caucasian cases. Neurological features of aceruloplasminemia in Caucasian patients were compared to those summarized in Japanese patients.Results: 21 Caucasian patients, both ours and the described cases, displayed a wide range of movement disorders with predominant chorea, parkinsonism and ataxia, and also tremor and dystonia. In addition to cognitive decline, nearly half of the Caucasian patients presented with psychiatric changes, including depression, anxiety and behavioral changes. In one-third of the neurologically symptomatic Caucasian patients, cognitive- or psychiatric changes were the first neurological manifestations of aceruloplasminemia.Conclusions: Aceruloplasminemia in Caucasian patients can present with a wider range and a different order of neurological symptoms than previously described in Japanese patients. Psychiatric changes and parkinsonism can be added to the spectrum of neurological disease. Cognitive- or psychiatric changes may be the first neurological manifestations of aceruloplasminemia. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
24. Progression of a solitary plasmacytoma to multiple myeloma. A population-based registry of the northern Netherlands.
- Author
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Waal, Esther G. M., Leene, Marnix, Veeger, Nic, Vos, Hanneke J., Ong, Francisca, Smit, Wilma G. J. M., Hovenga, Sjoerd, Hoogendoorn, Mels, Hogenes, Marieke, Beijert, Max, Diepstra, Arjan, and Vellenga, Edo
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PLASMACYTOMA , *MULTIPLE myeloma , *RADIOTHERAPY complications , *DISEASE progression , *NEOVASCULARIZATION , *DISEASE risk factors - Abstract
Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma ( MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors ( HIF), vascular endothelial growth factor ( VEGF, also termed VEGFA) and micro-vessel density ( MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma ( EMP) while 66% had a solitary plasmacytoma of the bone ( SBP). Median follow-up was 89 months, (7-293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2α (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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25. 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.
- Author
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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]
- Published
- 2014
- Full Text
- View/download PDF
26. Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK).
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Ossenkoppele, Gert J., Stussi, Georg, Maertens, Johan, Montfort, Kees van, Biemond, Bart J., Breems, Dimitri, Ferrant, August, Graux, Carlos, de Greet, Georgine E., Halkes, C. J. M., Hoogendoorn, Mels, Hollestein, Rene M., Jongen-Lavrencic, Mojca, Levin, Mark D., van de Loosdrecht, Arjan A., Marwijk Kooij, Marinus van, Norden, Yvette van, Pabst, Thomas, Schouten, Harry C., and Vellenga, Edo
- Subjects
- *
BEVACIZUMAB , *ACUTE myeloid leukemia , *CYTARABINE , *CLINICAL trials , *DRUG therapy , *CANCER research - Abstract
An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm.(n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic out-come of older AML patients. This trial is registered as number NTR904 in The Netherlands Trial Register (www.trialregister.nI). [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme
- Author
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van der Helm, Lieke H., Alhan, Canan, Wijermans, Pierre W., van Marwijk Kooy, Marinus, Schaafsma, Ron, Biemond, Bart J., Beeker, Aart, Hoogendoorn, Mels, van Rees, Bastiaan P., de Weerdt, Okke, Wegman, Jurgen, Libourel, Ward J., Luykx-de Bakker, Sylvia A., Minnema, Monique C., Brouwer, Rolf E., Croon-de Boer, Fransien, Eefting, Matthijs, Jie, Kon-Siong G., van de Loosdrecht, Arjan A., and Koedam, Jan
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- *
CHRONIC myeloid leukemia , *ACUTE myeloid leukemia , *AZACITIDINE , *MULTIVARIATE analysis , *DRUG administration - Abstract
Summary The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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28. Do not give paraffin to packers.
- Author
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Visser, Loes, Stricker, Bruno, Hoogendoorn, Mels, and Vinks, Alexander
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DRUG traffic , *COCAINE , *PEOPLE with drug addiction , *DRUG overdose , *PARAFFIN wax , *CARING , *CASE studies , *HEALTH - Abstract
Presents a medical case report of a man who died after ingesting 102 latex packages of cocaine to smuggle aboard a plane. How he began to feel on arrival to the airport; His treatment at the hospital; His death as a result of cardiovascular and respiratory failure due to cocaine intoxication; How he was treated with a mineral oil that may have contributed to the rupture of the packages; The conclusion that liquid paraffin not be used as a laxative for body-packers.
- Published
- 1998
- Full Text
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29. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS.
- Author
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Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, and Jongen-Lavrencic, Mojca
- Subjects
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THERAPEUTIC use of antineoplastic agents , *MYELODYSPLASTIC syndromes , *DRUG efficacy , *GLYCINE , *CONFIDENCE intervals , *CANCER chemotherapy , *ACUTE myeloid leukemia , *PROTEOLYTIC enzymes , *ANTINEOPLASTIC agents , *ATRIAL fibrillation , *CANCER patients , *RANDOMIZED controlled trials , *COMPARATIVE studies , *INFECTION , *SURVIVAL analysis (Biometry) , *DESCRIPTIVE statistics , *STATISTICAL sampling , *CYTARABINE , *HYDROXY acids , *LONGITUDINAL method , *CHEMICAL inhibitors , *EVALUATION , *OLD age - Abstract
Simple Summary: Treatment results of acute myeloid leukemia (AML) in elderly patients are unsatisfactory. We investigated in an open label randomized phase II study whether addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy would improve outcome in this population. 231 AML patients > 65 years of age were randomly assigned to receive standard chemotherapy with or without tosedostat for two cycles. We found that complete bone marrow leukemia clearance was not significantly different between both arms. After two years, survival was 33% for the standard arm versus 18% for the tosedostat arm. More patients died due to infectious complications in the tosedostat arm than after standard treatment. Also, a cardiac rhythm abnormality called atrial fibrillation was more often seen in the tosedostat arm. We conclude that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly patients with acute myeloid leukemia. Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
30. Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study.
- Author
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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.
- Subjects
- *
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]
- Published
- 2020
- Full Text
- View/download PDF
31. Influence of WHO versus ELN advanced phase chronic myeloid leukemia definitions on overall survival.
- Author
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Geelen, Inge G.P., Thielen, Noortje, Janssen, Jeroen J.W.M., Levin, Mark‐David, Hoogendoorn, Mels, Visser, Otto, Cornelissen, Jan J., and Westerweel, Peter E.
- Subjects
- *
CHRONIC myeloid leukemia , *HEALTH outcome assessment , *PATIENTS - Published
- 2017
- Full Text
- View/download PDF
32. Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion.
- Author
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Mihajlović, Jovan, Bax, Pieter, van Breugel, Erwin, Blommestein, Hedwig M., Hoogendoorn, Mels, Hospes, Wobbe, and Postma, Maarten J.
- Abstract
Purpose The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands. Methods Using a prospective, observational, bottom-up microcosting study, we collected primary data on the direct medical costs of the preparation, administration, and acquisition of rituximab. Drug costs and costs of drug wastage, labor costs, material costs, and outpatient costs were identified using standardized forms, structured using prices from official pricelists, and compared for the intravenous and subcutaneous forms of rituximab. Findings Measurements were taken on 53 rituximab administrations (33 intravenous and 20 subcutaneous) and on 13 rituximab preparation (7 intravenous and 6 subcutaneous). The mean total costs were €2176.77 for the intravenous infusion and €1911.09 for the subcutaneous injection. The estimated difference of €265.17 (95% CI, €231.99–`€298.35) per administration was mainly attributable to differences in time spent in the chemotherapy unit, related outpatient costs, drug wastage, and drug costs. Implications Rituximab administered in the form of subcutaneous injection is less costly than its intravenous form. With their equal effectiveness taken into account, subcutaneous rituximab administration can result in significant savings when transferred to the total diffuse large B-cell lymphoma population in the Netherlands. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
33. Implications of chills.
- Author
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Van Dissel, Jaap T., Schijf, Vicky, Vogtlander, Nils, Hoogendoorn, Mels, Van't Wout, Jan, Van Dissel, J T, Schijf, V, Vogtländer, N, Hoogendoorn, M, and van't Wout, J
- Subjects
- *
SPASMS , *SYMPTOMS , *DIAGNOSIS of bacterial diseases , *BACTEREMIA , *BACTERIAL diseases , *CYTOKINES , *ENDOTOXINS , *FEVER , *GRAM-negative bacterial diseases , *INTERLEUKINS , *LONGITUDINAL method , *SHOCK (Pathology) , *TUMOR necrosis factors , *PREDICTIVE tests , *SHIVERING ,RESEARCH evaluation - Abstract
Investigates how often chills are associated with bacterial infections, endotoxaemia, and cytokinaemia. Details of research done; Findings.
- Published
- 1998
- Full Text
- View/download PDF
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