Zwaan group

PI: Prof.dr. Michel Zwaan

 Laboratory research

The research program on myeloid leukemias is done in close collaboration with PIs in the Máxima Research Insititute, including the Stam group, the Van Boxtel group and the Heidenreich group. The program focuses on identifying determinants of clinical outcome to improve risk-group stratification, and to identify novel options for targeted treatment. Close collaboration exists with Dr. Tanja Gruber from St Jude Children’s research hospital (Memphis, USA), Dr Soheil Meshinchi from the Children’s Oncology Group (Seattle, USA), and Prof. Dirk Reinhardt from the BFM Group (Essen, Germany). Down ALL projects are performed in close collaboration with the Den Boer group.

Clinical Research

The early clinical trial program includes clinical studies of promising novel agents for children with cancer, and in addition focuses on therapeutic drug monitoring, bioequivalence studies of pediatric-friendly formulations, and age-dependent pharmacokinetics/dynamics.

Dr. Erica Brivio is appointed as fellow in pediatric drug development at the Trial and data center. Each of the units has a dedicated pediatric oncologist with a focus on early clinical trials:

  Fellow in pediatric drug development:          

• Erica Brivio (Bosutinib and Inotuzumab Ozogamicin studies)
• Lenneke Schrier (Neuroblastoma phase 1B basket trial)
  
  Hematological malignancies Unit
• Inge van der Sluis
• Britta Vormoor
• Auke Beishuizen (lymphoma)
• Caroline Lindemans (SCT)
  
  Solid tumor Unit 
• Natasha van Eijkelenburg
• Miranda Dierselhuis (fellow pediatric oncology)
  
  Brain tumor Unit
• Jasper van der Lugt
• Dannis van Vuurden (pontine glioma)
  
  PhD students:
  
  

  Sebastiaan Sassen Ron Mathôt (AMC) Towards evidence-based use of ciprofloxacin prophylaxis and glucocorticoids for children with cancer Natasha van Eijkelenburg   Drug development studies in pediatric oncology Laura Nijstad Alwin Huitema (NKI and UMCU) Pharmacokinetics and pharmacodynamics of antineoplastic agents in pediatric patients Erica Brivio   Early clinical trials in children with leukemia

  
  

   

  Key publications

  Gore L, Kearns PR, de Martino Lee ML, De Souza CA, Bertrand Y, Hijiya N, Stork LC, Chung NG, Cardos RC, Saikia T, Fagioli F, Seo JJ, Landman-Parker J, Lancaster D, Place AE, Rabin KR, Sacchi M, Swanink R, Zwaan CM. Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial. J Clin Oncol. 2018 May 1;36(13):1330-1338
  
  Van Eijkelenburg NKA, Rasche M, Ghazaly E, Dworzak MN, Klingebiel T, Rossig C, Leverger G, Stary J, de Bont ESJM, Chitu DA, Bertrand Y, Brethon B, Strahm B, van der Sluis IM, Kaspers GJL, Reinhardt D, Zwaan CM. Clofarabine, high-dose cytarabine and liposomal daunorubicin in pediatric relapsed/refractory acute myeloid leukemia: a phase IB study. Haematologica. 2018 Sep;103(9):1484-1492 PubMed PMID: 29498925

  Bolouri H, Farrar JE, Triche T Jr, Ries RE, Lim EL, Alonzo TA, Ma Y, Moore R, Mungall AJ, Marra MA, Zhang J, Ma X, Liu Y, Liu Y, Auvil JMG, Davidsen TM, Gesuwan P, Hermida LC, Salhia B, Capone S, Ramsingh G, Zwaan CM, Noort S, Piccolo SR, Kolb EA, Gamis AS, Smith MA, Gerhard DS, Meshinchi S. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med. 2018:Jan 24(1):103-112 PubMed PMID: 29227476 

  Moreno L, Pearson ADJ, Paoletti X, Jimenez I, Geoerger B, Kearns PR, Zwaan CM, Doz F, Baruchel A, Vormoor J, Casanova M, Pfister SM, Morland B, Vassal G; Innovative Therapies for Children with Cancer (ITCC) Consortium. Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective. Nat Rev Clin Oncol. 2017 Aug;14(8):497-507 PubMed PMID: 28508875

  Pearson ADJ, Pfister SM, Baruchel A, Bourquin JP, Casanova M, Chesler L, Doz F, Eggert A, Geoerger B, Jones DTW, Kearns PR, Molenaar JJ, Morland B, Schleiermacher G, Schulte JH, Vormoor J, Marshall LV, Zwaan CM, Vassal G; Executive and Biology Committees of the Innovative Therapies for Children with Cancer European Consortium. From class waivers to precision medicine in paediatric oncology. Lancet Oncol. 2017 Jul;18(7):e394-e404 PubMed PMID: 28677575 

  Madita Uffmann, Mareike Rasche, Martin Zimmermann, Christine von Neuhoff, Ursula Creutzig, Michael Dworzak, Lenie Scheffers, Henrik Hasle, C. Michel Zwaan, Dirk Reinhardt, and Jan-Henning Klusmann. Therapy reduction in patients with Down Syndrome Myeloid Leukemia: The international ML-DS 2006 trial. Blood 2017 Jun 22;129(25):3314-3321 PubMed PMID: 28400376

  De Rooij JD, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, Obulkasim A, Dang J, Easton J, Verboon LJ, Mulder HL, Zimmermann M, Koss C, Gupta P, Edmonson M, Rusch M, Lim JY, Reinhardt K, Pigazzi M, Song G, Yeoh AE, Shih LY, Liang DC, Halene S, Krause DS, Zhang J, Downing JR, Locatelli F, Reinhardt D, van den Heuvel-Eibrink MM, Zwaan CM, Fornerod M, Gruber TA. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet. 2017 Mar;49(3):451-456 PubMed PMID: 28112737

  Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M. Trippett, Carmelo Rizzari, Peter Bader, Maureen M. O’Brien, Benoˆıt Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R. Rheingold, Todd Michael Cooper, Christian M. Zwaan, Phillip Barnette, Chiara Messina, Gerard Michel, Steven G. DuBois, Kuolung Hu, Min Zhu, James A. Whitlock, and Lia Gore. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389 PubMed PMID: 27998223 

  Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R, De Bont ES, De Moerloose B, Dworzak M, Gibson BE, Hasle H, Leverger G, Locatelli F, Ragu C, Ribeiro RC, Rizzari C, Rubnitz JE, Smith OP, Sung L, Tomizawa D, van den Heuvel-Eibrink MM, Creutzig U, Kaspers GJ. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2015 Sep 20;33(27):2949-62 PubMed PMID: 26304895

  Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):385-94 PubMed PMID: 25770814

  Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM, Pieters R, Korbijn CM, Silverman LB, Schmiegelow K, Liang DC, Horibe K, Arico M, Biondi A, Basso G, Rabin KR, Schrappe M, Cario G, Mann G, Morak M, Panzer-Grümayer R, Mondelaers V, Lammens T, Cavé H, Stark B, Ganmore I, Moorman AV, Vora A, Hunger SP, Pui CH, Mullighan CG, Manabe A, Escherich G, Kowalczyk JR, Whitlock JA, Zwaan CM. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014 Jan 2;123(1):70-7 PubMed PMID: 24222333
  
  Prof.dr. Michel Zwaan's publications can be found on PubMed.