Journal of Neuro-Oncology

, Volume 97, Issue 2, pp 247–255

A phase II prospective study of sequential myeloablative chemotherapy with hematopoietic stem cell rescue for the treatment of selected high risk and recurrent central nervous system tumors

  • Amy Rosenfeld
  • Morris Kletzel
  • Reggie Duerst
  • David Jacobsohn
  • Paul Haut
  • Joanna Weinstein
  • Alfred Rademaker
  • Colleen Schaefer
  • Lauren Evans
  • Molly Fouts
  • Stewart Goldman
Clinical Study - Patient Study

Abstract

High risk/recurrent CNS tumors have a poor prognosis. We studied tandem high dose chemotherapy (HDC) with hematopoietic progenitor stem cell rescues (HPCR) as potentially curative therapy. Twenty-four patients (mean age 6.8 years) were enrolled, 19 underwent HDC/HPCR. Diagnoses were medulloblastoma (n = 9), germ cell tumor (n = 4), high grade astrocytoma (n = 2), supratentorial PNET (n = 1), pineoblastoma (n = 2), or papillary meningioma (n = 1). Cytoreduction regimen #1 consisted of carboplatin (500 mg/m2) × 3 days, etoposide (250 mg/m2) × 3 days, and thiotepa (300 mg/m2) × 3 days. Patients without progression or excessive toxicity (n = 11), received regimen #2 with melphalan (60 mg/m2) × 3 days and cyclophosphamide (1,500 mg/m2) × 4 days. Projected overall/event-free survival for the 19 patients was 51/37% and 34/28% at 1 and 5 years, respectively. Toxicity was significant with six treatment related deaths including four with veno-occlusive disease. This regimen of sequential HDC/HPCR in high risk/recurrent CNS tumor patients is not feasible due to toxicity.

Keywords

Pediatric high risk and brain tumors Pediatric recurrent brain tumors Myeloablative Chemotherapy Hematopoietic stem cell rescue 

References

  1. 1.
    Mahoney DH, Strother D, Camitta B, Bowen T, Ghim T, Pick T, Wall D, Yu L, Shuster J, Friedman H (1996) High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study. J Clin Oncol 14:382–388PubMedGoogle Scholar
  2. 2.
    Perez-Martinez A, Lassaletta A, Gonzalez-Vincent M, Sevilla J, Diaz A, Madero L (2005) High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol 71:33–38CrossRefPubMedGoogle Scholar
  3. 3.
    Modak S, Gardner S, Dunkel I, Balmaceda C, Rosenblum M, Miller D, Halpern S, Finlay J (2004) Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol 22:1934–1943CrossRefPubMedGoogle Scholar
  4. 4.
    George R, Li S, Medeiros-Nacarrow C, Neuberg D, Marcus K, Shamberger R, Pulsipher M, Grupp S, Diller L (2006) High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol 24:2891–2896CrossRefPubMedGoogle Scholar
  5. 5.
    Kletzel M, Katzenstein H, Haut P, Yu A, Morgan E, Reynolds M, Geissler G, Marymount M, Liu D, Kalapurakal J, Shore R, Bardo D, Schmoldt J, Rademaker A, Cohn S (2002) Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem cell rescue: results of the Chicago Pilot II Study. J Clin Oncol 20:2284–2292CrossRefPubMedGoogle Scholar
  6. 6.
    Jakacki R, Siffert J, Jamison C, Velasquez L, Allen J (1999) Dose-intensive, time compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. J Neurooncol 44:77–83CrossRefPubMedGoogle Scholar
  7. 7.
    Jakacki R, Jamison C, Heifetz S, Caldemeyer K, Hanna M, Sender L (1997) Feasibility of sequential high-dose chemotherapy and peripheral blood stem cell support for pediatric central nervous system malignancies. Med Pediatr Oncol 29:553–559CrossRefPubMedGoogle Scholar
  8. 8.
    Ozkaynak M, Sandoval C, Levendoglu-Tugal O, Jayabose S (2004) A pilot trial of tandem autologous peripheral blood progenitor cell transplantation following high-dose thiotepa and carboplatin in children with poor-risk central nervous system tumors. Pediatr Hematol Oncol 21:635–645CrossRefPubMedGoogle Scholar
  9. 9.
    Finlay J, Goldman S, Wong M, Cairo M, Garvin J, August C, Cohen B, Stanley P, Zimmerman R, Bostrom B, Geyer R, Harris R, Sanders J, Yates A, Boyett J, Packer R (1996) Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. J Clin Oncol 14:2495–2503PubMedGoogle Scholar
  10. 10.
    Cheuk D, Lee T, Chiang A, Ha S, Chan G (2008) Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children. J Neurooncol 86:337–347CrossRefPubMedGoogle Scholar
  11. 11.
    Dunkel I, Boyett J, Yates A, Rosenblum M, Garvin J, Bostrom B, Goldman S, Sender L, Gardner S, Li H, Allen J, Finlay J (1998) High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. J Clin Oncol 16:222–228PubMedGoogle Scholar
  12. 12.
    Graham M, Herndon J, Casey J, Chaffee S, Ciocci G, Krischer J, Kurtzberg J, Laughlin M, Longee D, Olson J, Paleologus N, Pennington C, Friedman H (1997) High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors. J Clin Oncol 15:1814–1823PubMedGoogle Scholar
  13. 13.
    Lee ET (2000) Statistical methods for survival data analysis. Wiley, New YorkGoogle Scholar
  14. 14.
    Gooley T, Leisenring W, Crowley J, Storer B (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:695–706CrossRefPubMedGoogle Scholar
  15. 15.
    Gururangan S, Dunkel I, Goldman S, Garvin J, Rosenblum M, Boyett J, Gardner S, Merchant T, Gollamudi S, Finlay J (1998) Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors. J Clin Oncol 16:2486–2493Google Scholar
  16. 16.
    Papadakis V, Dunkel I, Cramer L, Kramer E, Papadopoulos E, Goldman S, Packer R, Willoughby M, Baker D, Garvin J, Strandjord S, Coccia P, Kaplan A, Klemperer M, Finlay J (2000) High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors. Bone Marrow Transplant 26:153–160CrossRefPubMedGoogle Scholar
  17. 17.
    Papadopoulos K, Garvin J, Fetell M, Vahdat L, Garrett T, Savage D, Balmaceda C, Bruce J, Sisti M, Isaacson S, De LaPaz R, Hawks R, Bagiella E, Antman K, Hesdorffer C (1998) High-dose thiotepa and etoposide-based regimens with autologous hematopoietic support for high-risk or recurrent CNS tumors in children and adults. Bone Marrow Transplant 22:661–667CrossRefPubMedGoogle Scholar
  18. 18.
    Jonge M, Huitema A, Beijnen J, Rodenhuis S (2006) High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy. Br J Cancer 94:1226–1230CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Amy Rosenfeld
    • 1
  • Morris Kletzel
    • 2
  • Reggie Duerst
    • 2
  • David Jacobsohn
    • 2
  • Paul Haut
    • 3
  • Joanna Weinstein
    • 2
  • Alfred Rademaker
    • 4
  • Colleen Schaefer
    • 2
  • Lauren Evans
    • 2
  • Molly Fouts
    • 2
  • Stewart Goldman
    • 2
  1. 1.Center for Cancer and Blood DisordersPhoenix Children’s HospitalPhoenixUSA
  2. 2.Division of Hematology, Oncology, TransplantationChildren’s Memorial Hospital Box #30ChicagoUSA
  3. 3.Section of Hematology/OncologyIndiana University School of MedicineIndianapolisUSA
  4. 4.Department of Preventative MedicineFeinberg School of Medicine Northwestern UniversityChicagoUSA

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