Clinical Research Program – Hemato-oncology

Innovation in hematology-oncology

Together we are driving innovation in hemato-oncology. As clinical director, Josef Vormoor leads a team of healthcare professionals and as clinician scientist, he wants to know how the leukemic bone marrow micro-environment works.

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Josef Vormoor

Pediatric oncologist, Clinical director hemato-oncolody

Profile & contact

Clinical program

Within our hemato-oncology program, we treat children and young people with leukemia, lymphoma and certain other related blood disorders, such as bone marrow failure and histiocytosis. Our stem cell transplantation team (a collaboration with the Wilhelmina Children’s Hospital) is embedded within our program.

Our ultimate goal is to cure every child with leukemia/lymphoma with optimal quality of life. Close links between research and clinical care are essential to enable innovation and we have established several disease specific and cross-cutting teams via our Máxima Comprehensive Childhood Cancer Center (M4C). Through these M4C groups, we run a broad portfolio of innovative clinical trials.

A key focus of our program has been the implementation and development of immunotherapy (including cellular immunotherapy, such as CAR T cell therapy) for children with hematological malignancies.

“The bone marrow micro-envrionment is key to our understanding how leukemia protects itself from (immuno-)therapy.”

Prof. dr. Josef Vormoor

Clinical program director Hemato-oncology

Dissecting and targeting the bone marrow envrionment

Josef Vormoor's research is focused on understanding the interactions between acute lymphoblastic leukemia (ALL) blasts and their microenvironment. Using single cell sequencing, we have identified adipocyte progenitors as a novel key niche component in ALL. We also study how RAS mutations help ALL cells to reprogram their (immune) micro-environment. In our Research Institute, we work closely together with a group of top scientists, all with a common focus on the bone marrow micro-environment:

Prof. Monique den Boer
Dr Mirjam Belderbos
Prof. Olaf Heidenreich.

Our mutual aim is to identify vulnerabilities in the interaction of the leukemic blasts with the bone marrow environment that can be exploited for novel therapies.

Key publications
1. Ferrao Blanco MN, Kazybay B, Belderbos M, Heidenreich O, Vormoor HJ. Distinct Stromal Cell Populations Define the B-cell Acute Lymphoblastic Leukemia Microenvironment. bioRxiv preprint doi: https://doi.org/10.1101/2024.09.10.612346 .
2. George SL, Lynn C, Stankunaite R, Hughes D, Sauer CM, Chalker J, Waqar Ahmed S, Oostveen M, Proszek PZ, Yuan L, Shaikh R, Jamal S, Brew A, Tall J, Rogers T, Clifford SC, Vormoor J, Shipley JM, Tweddle DA, Jones C, Willis C, Burke GAA, Vedi A, Howell L, Johnston R, Rees H, Adams M, Jesudason A, Ronghe M, Elliott M, Ross E, Makin G, Campbell-Hewson Q, Grundy RG, Turnbull J, Wilson S, Lee V, Gray JC, Stoneham S, Gatz SA, Marshall LV, Angelini P, Anderson J, Cresswell GD, Graham TA, Al-Lazikani B, Cortes-Ciriano I, Kearns P, Hutchinson JC, Hargrave D, Jacques TS, Hubank M, Sottoriva A, Chesler L. Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states. Cancer Discov. 2024 Dec 19. doi: 10.1158/2159-8290.CD-24-0916.
3. Rossig C, Pearson AD, Vassal G, Scobie N, Bird N, Blanc P, Vormoor HJ, Calkoen FG, Locatelli F, Bufalo FD, Rives S, Jacoby E, Balduzzi A, Bourquin JP, Baruchel A; International BFM Study Group (I-BFM), Innovative Therapies for Children with Cancer (ITCC), and the European Society for Paediatric Oncology (SIOPE). Chimeric Antigen Receptor (CAR) T-Cell Products for Pediatric Cancers: Why Alternative Development Paths Are Needed. J Clin Oncol. 2024 Jan 20;42(3):253-257. doi: 10.1200/JCO.23.01314. Epub 2023 Nov 27.
4. Slade D, Menne T, Irving J, Johnson S, Kearns PR, Plummer R, Savage J, Shenton G, , Veal GJ, Vormoor B, Vormoor J*, Billingham L*. Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult Acute Lymphoblastic Leukaemia (SeluDex): Study protocol for an international, two-phase, two-group, dose finding with expansion phase I/II trial. BMJ Open. 2022 Mar 4;12(3):e059872. doi: 10.1136/bmjopen-2021-059872. *Common senior authors
5. Pal D, Blair H, Boyd S, Angel HS, Nizami S, Isa A, Beckett M, Nelson R, Wilson A, Singh M, Sankar S, Tirtakusuma R, Sirintra N, Knill C, Fuller A, McNeill H, Russell L, Schwab C, Zhous P, Sinclair P, Coxhead J, Filby A, Halsey C, Allan JM, Harrison JC, Moorman A, Heidenreich O, Vormoor J. An ex vivo human bone marrow milieu identifies CDH2 as a driver of niche-mediated treatment resistance in leukaemia. Cell Rep Med. 2022 Aug 16;3(8):100717. doi: 10.1016/j.xcrm.2022.100717.
Grants
A high-throughput platform for ex vivo agent treatment in patient-derived acute myeloid leukemia cells, Kika, 01-08-2024 – 31-07-2028 Project Grant, 2024, (PI Professor dr Olaf Heidenreich), Co-PI