Mels Hoogendoorn

Medisch Centrum Leeuwarden · Department of Hematology

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 o...

Chronic lymphocytic leukemia (CLL)-related symptoms and morbidity related to the advanced age at diagnosis, impairs the well-being of older CLL 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 HOVON...

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 w...

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...

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. Treatmen...

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 D 3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D 3 regimen on achieving a...

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 registrie...

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 popula...

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, na...

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 C...

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 lymphocyti...

The a priori risk for infections in patients with myelodysplastic syndromes (MDS) is unknown. This study examines prescription rates of anti‐infective agents in MDS patients before and after diagnosis, in both in‐ and outpatient settings, to provide information on infection management in clinical practice. We performed a population‐based study usin...

Background: The majority of patients with myelodysplastic syndromes (MDS) needs regular blood transfusions and becomes transfusion dependent. Blood transfusions temporarily alleviate anemia-related symptoms, but can be accompanied by adverse events, like iron overload. In MDS patients with >20 blood transfusions and plasma ferritin levels >1000 µg/...

Background: For fit CLL patients (pts), continuous BTK inhibitor treatment is replacing CIT as standard of care in frontline setting, particularly in pts with unfavorable prognostic factors. The time limited combinations venetoclax plus obinutuzumab (GVe) and venetoclax plus rituximab (RVe) have produced high rates of undetectable minimal residual...

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 includin...

Background Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. Methods Cost-effectiveness was...

Purpose Peripheral neuropathy (PN) is common in patients with multiple myeloma (MM). We hypothesized that the relationship between hypovitaminosis D and PN described in diabetes mellitus patients may also be present in MM patients. Methods To study this potential association, we assessed the incidence of hypovitaminosis D (vitamin D < 75 nmol/L [=...

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...

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...

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 a...

BACKGROUND There has been a cultural shift toward patient engagement in health with a growing demand from patients to access their results. OBJECTIVE The Lymphoma InterVEntion [LIVE] trial was conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological...

Background: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. Objective: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psycholog...

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, ra...

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 He...

Background: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. Methods: Cost-effectiveness wa...

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabin...

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 pre-treatment, and to search for new proteomic markers that might be...

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compa...

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 bortezo...

Rationale: 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. Objective: To determine the effect of different treatment periods (1996-2000, 2001-2006 and 2007-2011) on the risk of fractures in patients with...

Introduction New strategies in the treatment of multiple myeloma (MM) have improved response rates, progression-free survival and overall survival (OS). Despite the advances in treatment, patients frequently experience adverse events such as chemotherapy-induced peripheral neuropathy (CIPN). CIPN decreases quality of life, and requires dose adjustm...

Introduction Bone lesions are one of the primary symptoms in multiple myeloma (MM), and it has been suggested that these lesions adversely impact overall survival (OS). In the last decades, intensified supportive care and new treatment strategies were introduced to improve overall survival and quality of life. Bortezomib may have the capacity to st...

The majority of patients with myelodysplastic syndromes (MDS) require regular red blood cell (RBC) transfusions. Alloimmunization (AI) against blood products is an adverse event, causing time-consuming RBC compatibility testing. The reported incidence of AI in MDS patients varies greatly. Even though different studies on AI in MDS patients have bee...

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 lin...

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...

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‐immunot...

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...

7507 Background: This randomized phase III trial assessed whether intensification of rituximab (R) during the first 4 cycles of R-CHOP can improve outcome of diffuse large B-cell lymphoma (DLBCL) patients compared with standard R-CHOP. Patients in complete remission (CR) after induction treatment were randomized between rituximab maintenance and ob...

Early data on venetoclax-containing regimens for the treatment of chronic lymphocytic leukemia (CLL) show promising results with deep remissions, but are hampered by potential risk for tumor lysis syndrome (TLS). Whether optimal duration of venetoclax treatment can be guided by minimal residual disease (MRD) is currently unknown. To study whether T...

Introduction Chronic lymphocytic leukemia (CLL) is characterized by a profound immune suppression. In addition, CLL cells evade immune destruction by interacting with cells of the adaptive immune system, resulting in dysfunctional T cells. CD4+ T cells are skewed towards a TH2-profile and the number of regulatory T (Treg) cells, that diminish cellu...

Background: Lenalidomide (Len) has been proven effective both as monotherapy and in combination with rituximab for the treatment of chronic lymphocytic leukemia (CLL). Len has shown a distinct and more difficult to manage toxicity profile in the context of CLL, potentially hampering combination treatment with this drug. Methods: In 1st-line CLL...

Figure S1. Type of treatment of the 122 patients with a stage I(E) diffuse large B‐cell lymphoma (DLBCL) who completed therapy according to tumour localization. In nodal DLBCL, abbreviated R‐CHOP plus involved field radiotherapy is favoured over R‐CHOP. In extranodal DLBCL, nearly half of patients received R‐CHOP. Figure S2. A. Overall survival (OS...

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,...

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). M...

Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From Januar...

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved p...

Follicular lymphoma (FL) is typically a slow growing cancer that can be effectively treated. Some patients undergo transformation to diffuse large B cell lymphoma (DLBCL), which is frequently resistant to chemotherapy and is generally fatal. Targeted sequencing of DNA and RNA was applied to identify mutations and transcriptional changes that accomp...

Real-world evaluations of the efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide population-based chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagn...

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 in...

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 immunohisto...

With great interest, we read the recent article by Söderlund et al. in your journal describing the incidence, patient characteristics and outcome of Swedish patients with chronic myeloid leukemia (CML) in accelerated phase (AP) or blast crisis (BC) (1). The authors compared observations in a Swedish population-based cohort to published intervention...

PurposeThis prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. Methods D...

Introduction: In patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival. Methods: A population-based cohort study was performed including 343 consecutive p...

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, administrat...

Kikuchi disease is a rare disorder with an unknown pathogenesis and a typically self-limiting natural course in predominantly previously healthy young women. Here we present a 54-year-old woman suffering from an overwhelming presentation of Kikuchi disease, associated with haemophagocytic syndrome, liver cell necrosis and nephrotic syndrome. She re...

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...

OBJECTIVE To determine equivalence of the mean anti-Xa activity [aXa] in patients with EGFR < 60 mL/min treated with a reduced therapeutic dose of nadroparin using the dosage guideline of the Dutch Federation of Nephrology (NfN) and patients with EGFR > 60 mL/min receiving a standard therapeutic dose of nadroparin. DESIGN Prospective, observational...

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 1...