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  1. Article ; Online: A tango of antibody and inhibitor.

    Zwaan, C Michel

    Blood

    2021  Volume 137, Issue 19, Page(s) 2571–2572

    MeSH term(s) Antibodies
    Chemical Substances Antibodies
    Language English
    Publishing date 2021-05-12
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2020010322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Targeting the innate immune system in pediatric and adult AML.

    Perzolli, Alicia / Koedijk, Joost B / Zwaan, C Michel / Heidenreich, Olaf

    Leukemia

    2024  

    Abstract: While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable ... ...

    Abstract While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable target antigens, a better understanding of the immunosuppressive tumor microenvironment is necessary for the design of novel immunotherapy approaches. To date, most immune characterization studies in AML have focused on T cells, while innate immune lineages such as monocytes, granulocytes and natural killer (NK) cells, received less attention. In solid cancers, studies have shown that innate immune cells, such as macrophages, myeloid-derived suppressor cells and neutrophils are highly plastic and may differentiate into immunosuppressive cells depending on signals received in their microenvironment, while NK cells appear to be functionally impaired. Hence, an in-depth characterization of the innate immune compartment in the TME is urgently needed to guide the development of immunotherapeutic interventions for AML. In this review, we summarize the current knowledge on the innate immune compartment in AML, and we discuss how targeting its components may enhance T cell-based- and other immunotherapeutic approaches.
    Language English
    Publishing date 2024-03-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-024-02217-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects.

    Brivio, Erica / Zwaan, C Michel

    Pediatric blood & cancer

    2019  Volume 66, Issue 5, Page(s) e27645

    Abstract: There is an increasing interest for anaplastic lymphoma kinase (ALK) inhibitors in pediatric oncology for specific entities such as ALK-driven inflammatory myofibroblastic tumor (IMT). IMT treatment can be challenging due to localization of the tumor and ...

    Abstract There is an increasing interest for anaplastic lymphoma kinase (ALK) inhibitors in pediatric oncology for specific entities such as ALK-driven inflammatory myofibroblastic tumor (IMT). IMT treatment can be challenging due to localization of the tumor and in rare cases of metastasis. When standard surgical treatment is not feasible, ALK inhibitors may play an important role, as recently reported for the first-generation ALK inhibitors (crizotinib). However, data on the second-generation ALK inhibitors are limited. We report two emblematic cases of IMT in pediatric patients, treated with the second-generation ALK inhibitor ceritinib in the context of a clinical trial (NCT01742286).
    MeSH term(s) Adolescent ; Anaplastic Lymphoma Kinase/antagonists & inhibitors ; Child ; Crizotinib/therapeutic use ; Humans ; Inflammation/drug therapy ; Inflammation/pathology ; Male ; Myofibroblasts/drug effects ; Myofibroblasts/pathology ; Neoplasms, Muscle Tissue/drug therapy ; Neoplasms, Muscle Tissue/pathology ; Prognosis ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Protein Kinase Inhibitors ; Crizotinib (53AH36668S) ; ALK protein, human (EC 2.7.10.1) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1)
    Language English
    Publishing date 2019-01-29
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.27645
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Limited sampling strategies for individualized BAX 855 prophylaxis in severe hemophilia A: in silico evaluation.

    Bukkems, Laura H / Goedhart, Tine M H J / Zwaan, C Michel / Cnossen, Marjon H / Mathôt, Ron A A

    Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

    2023  Volume 34, Issue 3, Page(s) 171–178

    Abstract: Objective: Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS ...

    Abstract Objective: Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS of a standard half-life (SHL) factor VIII (FVIII) concentrate in a clinical setting.
    Methods: Individual PK parameters of BAX 855 were estimated for 10 000 virtual patients with severe hemophilia A using Monte Carlo simulations. Several LSS consisting of 2-6 samples were examined based on patient burden, bias and accuracy of clearance, elimination half-life, volume of distribution and trough levels at 72 h (C72). Analyses were performed separately for adults and children <12 years.
    Results: The preferred LSS for BAX 855 consisted of three sampling points at 15-30 min, 48 h and 72 h for both adults (mean accuracy C72: 14.0% vs. 10.8% using six samples) and children (mean accuracy C72: 14.9% vs. 11.4% using six samples). The best strategy with two samples (peak, 48 h) resulted in an adequate, but lower accuracy than strategies with ≥3 samples (mean accuracy C72: 22.3%). The optimal combination of the LSS of SHL FVIII and BAX 855 led to six samples during four clinical visits.
    Conclusion: This in silico study has identified that two to three samples are necessary to estimate the individual PK of BAX-855 adequately. These samples can be collected in one or two clinical visits. When combining PK profiling of SHL FVIII and BAX 855, six samples during four clinical visits are needed.
    MeSH term(s) Adult ; Child ; Humans ; Factor VIII ; Hemophilia A/drug therapy ; Hemostatics/therapeutic use ; Half-Life
    Chemical Substances BAX 855 (5X3GF74R79) ; Factor VIII (9001-27-8) ; Hemostatics
    Language English
    Publishing date 2023-04-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 1033551-1
    ISSN 1473-5733 ; 0957-5235
    ISSN (online) 1473-5733
    ISSN 0957-5235
    DOI 10.1097/MBC.0000000000001204
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test.

    Touwslager, Robbert N H / Zwaan, C Michel / Bakker, Boudewijn / Lentjes, Eef G W M / Looijenga, Leendert H J / van Santen, Hanneke M

    Journal of pediatric endocrinology & metabolism : JPEM

    2024  Volume 37, Issue 5, Page(s) 482–485

    Abstract: Objectives: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy ... ...

    Abstract Objectives: Childhood cancer survivors are at risk for premature ovarian insufficiency, especially after treatment with alkylating agents. The objective of this report is to highlight a case in which this phenomenon caused a false-positive pregnancy test.
    Case presentation: A workup was performed in a 14-year-old girl with a positive pregnancy test. She was diagnosed with stage IV neuroblastoma of the left adrenal gland at the age of 4 years. She received extensive treatment, including alkylating agents, and had been diagnosed with premature ovarian insufficiency. An LH/hCG suppression test was performed using high dose 17 bèta-estradiol: hCG levels normalized.
    Conclusions: The pregnancy test was false-positive due to production of low amounts of hCG by the pituitary gland as a result of high LH concentrations following premature ovarian insufficiency. It may be helpful to perform the LH/hCG suppression test to prove pituitary origin of the hCG overproduction.
    MeSH term(s) Humans ; Female ; Primary Ovarian Insufficiency/diagnosis ; Primary Ovarian Insufficiency/pathology ; Adolescent ; Pregnancy ; Pregnancy Tests ; Neuroblastoma/complications ; Neuroblastoma/pathology ; Neuroblastoma/drug therapy ; Adrenal Gland Neoplasms/complications ; Adrenal Gland Neoplasms/pathology ; Adrenal Gland Neoplasms/diagnosis ; False Positive Reactions ; Luteinizing Hormone/blood ; Prognosis
    Chemical Substances Luteinizing Hormone (9002-67-9)
    Language English
    Publishing date 2024-04-15
    Publishing country Germany
    Document type Case Reports ; Journal Article
    ZDB-ID 1231070-0
    ISSN 2191-0251 ; 0334-018X
    ISSN (online) 2191-0251
    ISSN 0334-018X
    DOI 10.1515/jpem-2024-0019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Treating CD33-Positive de novo Acute Myeloid Leukemia in Pediatric Patients: Focus on the Clinical Value of Gemtuzumab Ozogamicin.

    Wijnen, Noa E / Koedijk, Joost B / Klein, Kim / Luesink, Maaike / Goemans, Bianca F / Zwaan, C Michel / Kaspers, Gertjan J L

    OncoTargets and therapy

    2023  Volume 16, Page(s) 297–308

    Abstract: Although survival in pediatric acute myeloid leukemia (AML) has increased considerably over the past decades, refractory disease and relapse rates remain high. Refractory and relapsed disease are difficult to treat, with overall survival rates less than ... ...

    Abstract Although survival in pediatric acute myeloid leukemia (AML) has increased considerably over the past decades, refractory disease and relapse rates remain high. Refractory and relapsed disease are difficult to treat, with overall survival rates less than 40-50%. Preventing relapse should, therefore, be one of the highest priorities. Current conventional chemotherapy regimens are hard to intensify due to associated toxic complications, hence more effective therapies that do not increase toxicity are needed. A promising targeted agent is the CD33-directed antibody-drug conjugate gemtuzumab ozogamicin (GO). Because CD33 is highly expressed on leukemic cells in the majority of AML patients, GO can be useful for a broad range of patients. Better relapse-free survival (RFS) after therapy including GO has been reported in several pediatric clinical trials; however, ambiguity about the clinical value of GO in newly diagnosed children remains. Treatment with GO in de novo AML patients aged ≥1 month, in combination with standard chemotherapy is approved in the United States, whereas in Europe, GO is only approved for newly diagnosed patients aged ≥15 years. In this review, we aimed to clarify the clinical value of GO for treatment of newly diagnosed pediatric AML patients. Based on current literature, GO seems to have additional value, in terms of RFS, and acceptable toxicity when used in addition to chemotherapy during initial treatment. Moreover, in
    Language English
    Publishing date 2023-04-29
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2495130-4
    ISSN 1178-6930
    ISSN 1178-6930
    DOI 10.2147/OTT.S263829
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  7. Article ; Online: Central nervous system disease in pediatric acute myeloid leukemia.

    Gruber, Tanja A / Zwaan, C Michel

    Pediatric blood & cancer

    2017  Volume 64, Issue 12

    MeSH term(s) Central Nervous System Diseases/etiology ; Central Nervous System Diseases/pathology ; Central Nervous System Diseases/therapy ; Central Nervous System Neoplasms/etiology ; Central Nervous System Neoplasms/therapy ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute/complications ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Male ; Prognosis ; Risk Factors
    Language English
    Publishing date 2017-08-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.26782
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  8. Article ; Online: Population pharmacokinetic modeling of factor concentrates in hemophilia: an overview and evaluation of best practice.

    Goedhart, Tine M H J / Bukkems, Laura H / Zwaan, C Michel / Mathôt, Ron A A / Cnossen, Marjon H

    Blood advances

    2021  Volume 5, Issue 20, Page(s) 4314–4325

    Abstract: The accuracy of pharmacokinetic (PK)-guided dosing depends on the clinical and laboratory data used to construct a population PK model, as well as the patient's individual PK profile. This review provides a detailed overview of data used for published ... ...

    Abstract The accuracy of pharmacokinetic (PK)-guided dosing depends on the clinical and laboratory data used to construct a population PK model, as well as the patient's individual PK profile. This review provides a detailed overview of data used for published population PK models for factor VIII (FVIII) and factor IX (FIX) concentrates, to support physicians in their choices of which model best suits each patient. Furthermore, to enhance detailed data collection and documentation, we do suggestions for best practice. A literature search was performed; publications describing prophylactic population PK models for FVIII and FIX concentrates based on original patient data and constructed using nonlinear mixed-effect modeling were included. The following data were collected: detailed demographics, type of product, assessed and included covariates, laboratory specifications, and validation of models. Included models were scored according to our recommendations for best practice, specifically scoring the quality of data documentation as reported. Respectively, 20 models for FVIII and 7 for FIX concentrates were retrieved. Although most models (22/27) included pediatric patients, only 4 reported detailed demographics. The wide range of body weights suggested that overweight and obese adults were represented. Twenty-six models reported the assay applied to measure factor levels, whereas only 16 models named reagents used. Eight models were internally validated using a data subset. This overview presents detailed information on clinical and laboratory data used for published population PK models. We provide recommendations on data collection and documentation to increase the reliability of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B.
    MeSH term(s) Adult ; Child ; Hemophilia A/drug therapy ; Hemostatics ; Humans ; Reproducibility of Results
    Chemical Substances Hemostatics
    Language English
    Publishing date 2021-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2021005096
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  9. Article ; Online: Thymus and activation-regulated chemokine (TARC) as treatment response marker for paediatric Hodgkin lymphoma: A pilot study.

    Zijtregtop, Eline A M / Diez, Claudius / Zwaan, C Michel / Veening, Margreet A / Beishuizen, Auke / Meyer-Wentrup, Friederike A G

    British journal of haematology

    2022  Volume 200, Issue 1, Page(s) 70–78

    Abstract: Classical Hodgkin lymphoma (cHL) is characterised by malignant Hodgkin Reed-Sternberg cells located in an inflammatory microenvironment. Blood biomarkers result from active cross-talk between malignant and non-malignant cells. One promising biomarker in ... ...

    Abstract Classical Hodgkin lymphoma (cHL) is characterised by malignant Hodgkin Reed-Sternberg cells located in an inflammatory microenvironment. Blood biomarkers result from active cross-talk between malignant and non-malignant cells. One promising biomarker in adult patients with cHL is thymus and activation-regulated chemokine (TARC). We investigated TARC as marker for interim and end-of-treatment response in paediatric cHL. In this multicentre prospective study, TARC levels were measured among 99 paediatric patients with cHL before each cycle of chemotherapy and were linked with interim and end-of-treatment remission status. TARC levels were measured by enzyme-linked immunosorbent assay. At diagnosis, TARC levels were elevated in 96% of patients. Plasma TARC levels declined significantly after one cycle of chemotherapy (p < 0.01 vs. baseline) but did not differ at interim assessment by positron emission tomography (p = 0.31). In contrast, median plasma TARC at end of treatment was significantly higher in three patients with progressive disease compared to those in complete remission (1.226 vs. 90 pg/ml; p < 0.001). We demonstrate that, in paediatric patients, plasma TARC is a valuable response marker at end-of-treatment, but not at interim analysis after the first two chemotherapy cycles. Further research is necessary to investigate TARC as marker for long-term progression free survival.
    MeSH term(s) Adult ; Humans ; Child ; Hodgkin Disease/therapy ; Chemokine CCL17/therapeutic use ; Pilot Projects ; Prospective Studies ; Chemokines ; Biomarkers ; Tumor Microenvironment
    Chemical Substances Chemokine CCL17 ; Chemokines ; Biomarkers
    Language English
    Publishing date 2022-09-20
    Publishing country England
    Document type Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18473
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  10. Article: Ibrutinib is not an effective drug in primografts of TCF3-PBX1.

    van de Ven, Cesca / Boeree, Aurélie / Stalpers, Femke / Zwaan, C Michel / Den Boer, Monique L

    Translational oncology

    2020  Volume 13, Issue 10, Page(s) 100817

    Abstract: Aim: The Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia. We previously showed that primary cells of children with TCF3-PBX1 positive ... ...

    Abstract Aim: The Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia. We previously showed that primary cells of children with TCF3-PBX1 positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) express BTK and are sensitive to ibrutinib in vitro. However, preclinical studies in mice are lacking that justify clinical implementation.
    Methods: Immunocompromised NSG mice were engrafted with a luciferase-positive TCF3-PBX1 leukemic cell line or primary leukemic cells and treated with ibrutinib or placebo. Additionally, primary cells were exposed in vitro to 4 main induction drugs as monotherapy and in combination with ibrutinib.
    Results: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice. In vitro sensitivity to ibrutinib was unaltered in leukemic cells obtained from engrafted mice compared to the original material. However, ibrutinib treatment did not affect leukemic cell viability and tumor outgrowth, nor could lymphocytosis be detected. Ibrutinib was biologically active, since hCD19
    Conclusions: We conclude that ibrutinib is not the precision medicine of choice for TCF3-PBX1 positive BCP-ALL.
    Language English
    Publishing date 2020-06-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233 ; 1936-5233 ; 1944-7124
    ISSN (online) 1936-5233
    ISSN 1936-5233 ; 1944-7124
    DOI 10.1016/j.tranon.2020.100817
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