المؤلفون: Alexandre G. Troullioud Lucas, Jaap Jan Boelens, Susan E. Prockop, Kevin J. Curran, Dorine Bresters, Wouter Kollen, Birgitta Versluys, Marc B. Bierings, Anne Archer, Eric Davis, Elizabeth Klein, Nancy A. Kernan, Caroline A. Lindemans, Andromachi Scaradavou

المصدر: Frontiers in Oncology, Vol 13 (2023)

مصطلحات موضوعية: cord blood transplant, relapse, second transplant, leukemia, treatment related mortality, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundPatients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment.MethodsWe retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray.ResultsTwenty-six patients age < 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR>2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients.ConclusionsSurvival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fonc.2023.1221782/full; https://doaj.org/toc/2234-943X

URL الوصول: https://doaj.org/article/4bbe82594c39483eb049ca274f54e3e9

المؤلفون: Katja I. Braam, Elisabeth M. van Dijk-Lokkart, Gertjan J. L. Kaspers, Tim Takken, Jaap Huisman, Laurien M. Buffart, Marc B. Bierings, Johannes H. M. Merks, Marry M. van den Heuvel-Eibrink, Margreet A. Veening, Eline van Dulmen-den Broeder

المصدر: BMC Cancer, Vol 18, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: Children, Cancer, Physical exercise, Psychosocial, Intervention, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Physical fitness and psychosocial function is often reduced in children during or shortly after cancer treatment. This study evaluates the effect of a combined physical exercise and psychosocial intervention on cardiorespiratory fitness, muscle strength, body composition, psychosocial function and health-related quality of life (HrQoL). In addition, intervention mediators, applicability and adherence were examined. Methods This multicenter randomized controlled trial included 68 children with cancer [mean age 13.2 (SD: 3.1) years; 54% male] during treatment or within 12-months post-treatment. The 12-week intervention consisted of 24 individual physical exercise sessions supervised by a physiotherapist, and 6 psychosocial training sessions for children and 2 for parents. Physical fitness and psychosocial function were assessed at baseline, directly post-intervention and at 12 months’ post-baseline. Generalized estimating equations were used to simultaneously assess intervention effects at short and long-term. Additionally, we evaluated within-group differences over time. Potential physical and psychosocial mediators in the intervention effect on HrQoL were examined using the product-of-coefficient test. Applicability and adherence were assessed by trainer-report. Results This study was able to compare 26 children who received the study intervention, with 33 children who received usual care. No significant differences in the effects of the intervention were found on physical fitness and psychosocial function at short-term. At 12-months follow-up, significantly larger improvements in lower body muscle strength (β = 56.5 Newton; 95% CI: 8.5; 104.5) were found in the intervention group when compared to the control group. Within-group changes showed significant improvements over time in HrQoL and bone density in both groups. Intervention effects on HrQoL were not significantly mediated by physical fitness and psychological function. Intervention applicability was satisfactory with an average session attendance of 67% and 22% dropout (mainly due to disease recurrence). Conclusions This 12-week physical exercise and psychosocial training intervention for children with cancer was applicable and showed satisfactory adherence. We found no significant between-group differences in effect, except for a significant improvement in lower body muscle strength at long-term in the intervention group compared to the control group. Yet, both the intervention and the control group showed improvements in bone mineral density and HrQoL over time. Trial registration The trial was registered at the Dutch Trial Registry (NTR1531). Registered 12 November 2008.

وصف الملف: electronic resource

Relation: http://link.springer.com/article/10.1186/s12885-018-5181-0; https://doaj.org/toc/1471-2407

URL الوصول: https://doaj.org/article/beed8505f08d45beb9195e8a8ba23e79

المؤلفون: Daan Vorselen, Susan M. van Dommelen, Raya Sorkin, Melissa C. Piontek, Jürgen Schiller, Sander T. Döpp, Sander A. A. Kooijmans, Brigitte A. van Oirschot, Birgitta A. Versluijs, Marc B. Bierings, Richard van Wijk, Raymond M. Schiffelers, Gijs J. L. Wuite, Wouter H. Roos

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-9 (2018)

مصطلحات موضوعية: Science

الوصف: Red blood cell disorders are often accompanied by increased release of extracellular vesicles (EVs), but their structural and mechanical properties are not fully understood. Here, the authors show that red blood cell EVs show liposome-like mechanical features and are softened in blood disorder patients.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/ee3d649d089e45a59a0d4b1fccb687f2

المؤلفون: Iris Nederlof, Caroline A. Lindemans, Marc B. Bierings, Alexander B. Mohseny, Dorine Bresters, Marije Bartels

المصدر: HemaSphere, Vol 3, Iss 4 (2019)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

Relation: http://journals.lww.com/10.1097/HS9.0000000000000282; https://doaj.org/toc/2572-9241

URL الوصول: https://doaj.org/article/9a66fcec74284dbea0b69f96c17df486

المؤلفون: Roel Polak, Marc B. Bierings, Cindy S. van der Leije, Mathijs A. Sanders, Onno Roovers, João R. M. Marchante, Judith M. Boer, Jan J. Cornelissen, Rob Pieters, Monique L. den Boer, Miranda Buitenhuis

المصدر: Haematologica, Vol 104, Iss 4 (2019)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Translocation t(12;21), resulting in the ETV6-RUNX1 (or TEL-AML1) fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia and is considered a first hit in leukemogenesis. A targeted therapy approach is not available for children with this subtype of leukemia. To identify the molecular mechanisms underlying ETV6-RUNX1-driven leukemia, we performed gene expression profiling of healthy hematopoietic progenitors in which we ectopically expressed ETV6-RUNX1. We reveal an ETV6-RUNX1-driven transcriptional network that induces proliferation, survival and cellular homeostasis. In addition, Vps34, an important regulator of autophagy, was found to be induced by ETV6-RUNX1 and up-regulated in ETV6-RUNX1-positive leukemic patient cells. We show that induction of Vps34 was transcriptionally regulated by ETV6-RUNX1 and correlated with high levels of autophagy. Knockdown of Vps34 in ETV6-RUNX1-positive cell lines severely reduced proliferation and survival. Inhibition of autophagy by hydroxychloroquine, a well-tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1-positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1-positive leukemia samples to L asparaginase. These findings reveal a causal relationship between ETV6-RUNX1 and autophagy, and provide pre-clinical evidence for the efficacy of autophagy inhibitors in ETV6-RUNX1-driven leukemia.

وصف الملف: electronic resource

Relation: https://haematologica.org/article/view/8848; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721

URL الوصول: https://doaj.org/article/4bd5df9ab18c4a7ea4cc4a5921e64071

المؤلفون: Lars T. van der Veken, Merel C. Maiburg, Floris Groenendaal, Mariëlle E. van Gijn, Andries C. Bloem, Claudia Erpelinck, Stefan Gröschel, Mathijs A. Sanders, Ruud Delwel, Marc B. Bierings, Arjan Buijs

المصدر: Haematologica, Vol 103, Iss 4 (2018)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

Relation: https://haematologica.org/article/view/8437; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721

URL الوصول: https://doaj.org/article/dae540236d204d36aa7a857abdb5195d

المؤلفون: Sebastiaan D.T. Sassen, Ron A.A. Mathôt, Rob Pieters, Robin Q.H. Kloos, Valérie de Haas, Gertjan J.L. Kaspers, Cor van den Bos, Wim J.E. Tissing, Maroeska te Loo, Marc B. Bierings, Wouter J.W. Kollen, Christian M. Zwaan, Inge M. van der Sluis

المصدر: Haematologica, Vol 102, Iss 3 (2017)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough concentrations to ensure adequate asparaginase activity (≥100 IU/L). The aim of this study was to describe the population pharmacokinetics of intravenous Erwinia asparaginase to quantify and gather insight into inter-individual and inter-occasion variability. The starting dose was evaluated on the basis of the derived population pharmacokinetic parameters. In a multicenter prospective observational study, a total of 714 blood samples were collected from 51 children (age 1–17 years) with acute lymphoblastic leukemia. The starting dose was 20,000 IU/m2 three times a week and adjusted according to trough levels from week three onwards. A population pharmacokinetic model was developed using NONMEM®. A 2-compartment linear model with allometric scaling best described the data. Inter-individual and inter-occasion variability of clearance were 33% and 13%, respectively. Clearance in the first month of treatment was 14% higher (P

وصف الملف: electronic resource

Relation: https://haematologica.org/article/view/8006; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721

URL الوصول: https://doaj.org/article/2272e63ed0f845619d1af21e29d1e8da

المؤلفون: Suzanna M. van Walraven, Anneke Brand, Jack N.A. Bakker, Martin B.A. Heemskerk, Suzan Nillesen, Marc B. Bierings, Laura B. Bungener, Bouke G. Hepkema, Arjan Lankester, Arnold van der Meer, Kees Sintnicolaas, Judith A.E. Somers, Eric Spierings, Marcel G.J. Tilanus, Christien E.M. Voorter, Jan J. Cornelissen, Machteld Oudshoorn

المصدر: Haematologica, Vol 102, Iss 1 (2017)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001–2006, n=995; 2007–2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were ‘donor found’ and ‘transplantation reached’. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P

وصف الملف: electronic resource

Relation: https://haematologica.org/article/view/7936; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721

URL الوصول: https://doaj.org/article/2e119e2cf43042ffbdff716d1171d545

المؤلفون: Ruben D. de Ruiter, M. Suzanne Gordijn, Reinoud J. B. J. Gemke, Cor van den Bos, Marc B. Bierings, Joost Rotteveel, Jan W. Koper, Elisabeth F. C. van Rossum, Gertjan L. Kaspers

المصدر: Haematologica, Vol 99, Iss 8 (2014)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

وصف الملف: electronic resource

Relation: https://haematologica.org/article/view/7126; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721

URL الوصول: https://doaj.org/article/eb90af7341f4415a948fefbe3cd13ed3

المؤلفون: Rick, Admiraal, Stefan, Nierkens, Marc B, Bierings, Robbert G M, Bredius, Ineke, van Vliet, Yilin, Jiang, Marta, Lopez-Yurda, A Birgitta, Versluijs, C Michel, Zwaan, Caroline A, Lindemans, Jaap Jan, Boelens

المساهمون: Pediatrics

المصدر: The Lancet Haematology, 9(2), e111-e120. Lancet Publishing Group

مصطلحات موضوعية: Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Humans, Female, Prospective Studies, Hematology, Neoplasm Recurrence, Local, Child, Antilymphocyte Serum

الوصف: Background: Anti-thymocyte globulin, which is used in the conditioning of haematopoietic stem-cell transplantation (HSCT) to prevent graft-versus-host disease (GVHD) and graft failure, has highly variable pharmacokinetics. Overexposure to anti-thymocyte globulin leads to poor CD4+ T-cell immune reconstitution, which is associated with inferior overall survival. We hypothesised that individualised anti-thymocyte globulin dosing would promote CD4+ immune reconstitution, while still preventing GVHD and graft failure. Methods: We report the results of a prospective, single-arm, phase 2 clinical trial done at the University Medical Center Utrecht and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands) to investigate individualised dosing of anti-thymocyte globulin for unrelated allogeneic HSCT in paediatric patients. Anti-thymocyte globulin dosing was based on bodyweight, absolute lymphocyte counts before the first dose, and the stem-cell source, with cumulative doses ranging from 2–10 mg/kg. Patients younger than 18 years receiving a first HSCT with a T-cell repleted graft for any indication and a Lansky/Karnofsky performance status of at least 70% were eligible for inclusion. The primary endpoint was CD4+ immune reconstitution (>0·05 × 109 CD4+ T-cells per L twice within 100 days [±3] after transplantation). The primary endpoint needed to be met in 38 of 53 evaluable patients (no death, relapse, or graft failure before day 100). Toxicity was registered according to Common Terminology Criteria for Adverse Events criteria version 4.0. The study is registered with the Dutch Trial Register, NL4836. Findings: Between July 1, 2015, and Aug 22, 2018, 58 patients were included in the study, of whom 51 were evaluable for the primary endpoint. Median follow-up was 25·6 months (IQR 15·0–37·0) and median age was 7·4 years (IQR 2·8–13·2). 29 (50%) of 58 patients were female. CD4+ immune reconstitution was reached in 41 (80%, 95% CI 67–90, in survival analysis) of 51 evaluable patients, hence the study met its primary endpoint. There was no difference in CD4+ immune reconstitution between patients who received different stem-cell sources (87% [95% CI 61–96] in cord blood, 77% [54–89] in bone marrow [p=0·62]). The most common grade 3–5 adverse events were infections (32 [50%] patients had grade 3, two [3%] patients had grade 4, and seven [11%] patients had fatal events) and immunological disorders (seven [11%] patients had grade 3, three [5%] patients had grade 4, and five [8%] patients had fatal events). Two (3%) of 64 patients died of GVHD, which might be indirectly related to the intervention. Interpretation: Individualised dosing of anti-thymocyte globulin led to a significant improvement in early CD4+ immune reconstitution without increasing GVHD and graft failure incidence. Promotion of early CD4+ immune reconstitution by individualising anti-thymocyte globulin dose might improve outcomes of allogeneic HSCT. Funding: Sanofi.

وصف الملف: application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f41c9f6d5007004ab5ec065beb7dfc0d
https://doi.org/10.1016/s2352-3026(21)00375-6