Skip to main content

Advertisement

SpringerLink
Log in

Recurrent Wnt medulloblastoma treated with marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue: a dual case report and review of the literature

  • Case Report
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Wnt-activated medulloblastoma (MB) confers an excellent prognosis. However, specific treatment strategies for patients with relapsed Wnt-MB are unknown. We report two patients with recurrent beta-catenin nucleopositive Wnt-MB successfully treated by incorporating marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue (HDCx/AuHPCR). We also present a review of the literature for previously reported cases of relapsed Wnt-MB. We propose that patients with recurrent Wnt-MB may be treated using a multi-disciplinary approach that includes HDCx/AuHPCR with or without re-irradiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MB:

Medulloblastoma

Wnt:

Wingless pathway

Wnt-MB:

Wnt-activated medulloblastoma

HDCx:

Marrow-ablative chemotherapy

AuHPCR:

Autologous hematopoietic progenitor cell rescue

CSI:

Craniospinal irradiation

MRI:

Magnetic resonance imaging

DWI:

Diffusion-weighted imaging

CSF:

Cerebrospinal fluid

GTR:

Gross total resection

FISH:

Fluorescence in situ hybridization

IHC:

Immunohistochemistry

R1:

First relapse

R2:

Second relapse

R3:

Third relapse

RT:

Radiotherapy

OS:

Overall survival

References

  1. Waszak SM, Northcott PA, Buchhalter I et al (2018) Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol 19(6):785–798. https://doi.org/10.1016/S1470-2045(18)30242-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Northcott PA, Robinson GW, Kratz CP et al (2019) Medulloblastoma. Nat Rev Dis Primers 5(1):11. https://doi.org/10.1038/s41572-019-0063-6

    Article  PubMed  Google Scholar 

  3. Cavalli FMG, Remke M, Rampasek L et al (2017) Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31(6):737–754.e6. https://doi.org/10.1016/j.ccell.2017.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S, Cho YJ, Shih DJ, Luu B, Dubuc AM, Northcott PA, Schüller U, Gururangan S, McLendon R, Bigner D, Fouladi M, Ligon KL, Pomeroy SL, Dunn S, Triscott J, Jabado N, Fontebasso A, Jones DTW, Kool M, Karajannis MA, Gardner SL, Zagzag D, Nunes S, Pimentel J, Mora J, Lipp E, Walter AW, Ryzhova M, Zheludkova O, Kumirova E, Alshami J, Croul SE, Rutka JT, Hawkins C, Tabori U, Codispoti KET, Packer RJ, Pfister SM, Korshunov A, Taylor MD (2013) Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14(12):1200–1207. https://doi.org/10.1016/S1470-2045(13)70449-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7(10):813–820. https://doi.org/10.1016/S1470-2045(06)70867-1

    Article  PubMed  Google Scholar 

  6. Rutkowski S, von Hoff K, Emser A, Zwiener I, Pietsch T, Figarella-Branger D, Giangaspero F, Ellison DW, Garre ML, Biassoni V, Grundy RG, Finlay JL, Dhall G, Raquin MA, Grill J (2010) Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. J Clin Oncol 28(33):4961–4968. https://doi.org/10.1200/JCO.2010.30.2299

    Article  PubMed  Google Scholar 

  7. Dagri JN, Evans A, Torkildson JC, Portnow J, Ashby LS, Zakotnik B, Brown RJ, Dhall G, Finlay JL (2014) Feasibility of an attenuated maintenance chemotherapy regimen directed at adolescents and young adults with newly diagnosed localized medulloblastoma and other central nervous system embryonal tumors. Journal of Adolescent and Young Adult Oncology 3(3):106–111. https://doi.org/10.1089/jayao.2013.0034

    Article  Google Scholar 

  8. Michalski J, Vezina G, Burger P et al (2016) MB-109: preliminary results of COG ACNS0331: a phase III trial of involved field radiotherapy (IFRT) and low dose craniospinal irradiation (LD-CSI) with chemotherapy in average risk medulloblastoma: a report from the Children’s Oncology Group. Neuro-Oncology 18(Suppl 3):iii122. https://doi.org/10.1093/neuonc/now076.104

    Article  PubMed Central  Google Scholar 

  9. Levy A, Krailo M, Chi S et al (2017) PDCT-09. Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma/CNS PNET of childhood: report of a COG randomized phase II screening trial. Neuro-Oncology 19(Suppl 6):vi186. https://doi.org/10.1093/neuonc/nox168.753

    Article  PubMed Central  Google Scholar 

  10. Sabel M, Fleischhack G, Tippelt S et al (2016) Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study. J Neuro-Oncol 129(3):515–524. https://doi.org/10.1007/s11060-016-2202-1

    Article  Google Scholar 

  11. Tsang DS, Sarhan N, Ramaswamy V, Nobre L, Yee R, Taylor MD, Hawkins C, Bartels U, Huang A, Tabori U, Hodgson DC, Bouffet E, Laperriere N (2019) Re-irradiation for children with recurrent medulloblastoma in Toronto, Canada: a 20-year experience. J Neuro-Oncol 145(1):107–114. https://doi.org/10.1007/s11060-019-03272-2

    Article  CAS  Google Scholar 

  12. Narayan V, Sugur H, Jaiswal J, Arvinda HR, Arivazhagan A, Somanna S, Santosh V (2019) Medulloblastoma: distinctive histo-molecular correlation with clinical profile, radiologic characteristics, and surgical outcome. Pediatr Neurosurg 54(5):329–340. https://doi.org/10.1159/000501913

    Article  PubMed  Google Scholar 

  13. Korshunov A, Sahm F, Zheludkova O et al (2019) DNA methylation profiling is a method of choice for molecular verification of pediatric WNT-activated medulloblastomas. Neuro-Oncology 21(2):214–221. https://doi.org/10.1093/neuonc/noy155

    Article  CAS  PubMed  Google Scholar 

  14. Bezerra Salomão K, Cruzeiro GAV, Bonfim-Silva R, Geron L, Ramalho F, Pinto Saggioro F, Serafini LN, Antunes Moreno D, de Paula Queiroz RG, dos Santos Aguiar S, Cardinalli I, Yunes JA, Brandalise SR, Brassesco MS, Scrideli CA, Gonzaga Tone L (2018) Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups. J Neuro-Oncol 139(1):33–42. https://doi.org/10.1007/s11060-018-2845-1

    Article  CAS  Google Scholar 

  15. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JEA, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352(10):978–986. https://doi.org/10.1056/NEJMoa042176

    Article  CAS  PubMed  Google Scholar 

  16. Johnston DL, Keene D, Strother D et al (2018) Survival following tumor recurrence in children with medulloblastoma. J Pediatr Hematol Oncol 40(3):e159–e163. https://doi.org/10.1097/MPH.0000000000001095

    Article  PubMed  Google Scholar 

  17. Guerra JA, Dhall G, Marachelian A, Castillo E, Malvar J, Wong K, Sposto R, Finlay JL (2017) Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors. Bone Marrow Transplant 52(11):1543–1548. https://doi.org/10.1038/bmt.2017.166

    Article  CAS  PubMed  Google Scholar 

  18. Espinoza JC, Haley K, Patel N et al (2016) Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: final report of the Head Start II and III trials. Pediatr Blood Cancer 63(10):1806–1813. https://doi.org/10.1002/pbc.26118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee SH, Son MH, Sung KW, Choi YB, Lee NH, Yoo KH, Koo HH, Lim DH, Shin HJ (2014) Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens for malignant brain tumors in children and young adults. J Neuro-Oncol 120(3):507–513. https://doi.org/10.1007/s11060-014-1576-1

    Article  CAS  Google Scholar 

  20. Dunkel IJ, Gardner SL, Garvin JH, Goldman S, Shi W, Finlay JL (2010) High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro-Oncology 12(3):297–303. https://doi.org/10.1093/neuonc/nop031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gill P, Litzow M, Buckner J, Arndt C, Moynihan T, Christianson T, Ansell S, Galanis E (2008) High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system. Cancer 112(8):1805–1811. https://doi.org/10.1002/cncr.23362

    Article  CAS  PubMed  Google Scholar 

  22. Gururangan S, Krauser J, Watral MA, Driscoll T, Larrier N, Reardon DA, Rich JN, Quinn JA, Vredenburgh JJ, Desjardins A, McLendon RE, Fuchs H, Kurtzberg J, Friedman HS (2008) Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma. Neuro-Oncology 10(5):745–751. https://doi.org/10.1215/15228517-2008-044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bode U, Zimmermann M, Moser O, Rutkowski S, Warmuth-Metz M, Pietsch T, Kortmann RD, Faldum A, Fleischhack G (2014) Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial. J Neuro-Oncol 120(3):635–642. https://doi.org/10.1007/s11060-014-1598-8

    Article  CAS  Google Scholar 

  24. Gajjar A (2008) High-dose chemotherapy for recurrent medulloblastoma: time for a reappraisal. Cancer 112(8):1643–1645. https://doi.org/10.1002/cncr.23352

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH, 43205, USA

    Micah K. Harris, Margaret Shatara, Zachary Funk, Joseph Stanek, Jonathan L. Finlay & Mohamed S. Abdelbaki

  2. The Ohio State University College of Medicine, Columbus, OH, 43210, USA

    Micah K. Harris

  3. The Division of Pediatric Hematology and Oncology, Washington University School of Medicine, 1 Children’s Pl, St. Louis, MO, 63011, USA

    Margaret Shatara & Mohamed S. Abdelbaki

  4. Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital and The Ohio State University, Columbus, Ohio, 43210, USA

    Daniel R. Boué

  5. The Department of Radiology, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA

    Jeremy Jones

Authors
  1. Micah K. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret Shatara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zachary Funk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joseph Stanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel R. Boué
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeremy Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jonathan L. Finlay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohamed S. Abdelbaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohamed S. Abdelbaki.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harris, M.K., Shatara, M., Funk, Z. et al. Recurrent Wnt medulloblastoma treated with marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue: a dual case report and review of the literature. Childs Nerv Syst 38, 465–472 (2022). https://doi.org/10.1007/s00381-021-05197-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-021-05197-6

Keywords

Search

Navigation