High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors

A Report From the Children's Oncology Group (CCG-99702)

Kellie J. Nazemi, Violet Shen, Jonathan L. Finlay, James Boyett, Mehmet Kocak, Deborah Lafond, Sharon L. Gardner, Roger J. Packer, H. Stacy Nicholson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). Procedure: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. Results: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m2/day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m2/day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%. Conclusions: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.

Original languageEnglish (US)
Pages (from-to)1563-1570
Number of pages8
JournalPediatric Blood and Cancer
Volume63
Issue number9
DOIs
StatePublished - Sep 1 2016

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Craniospinal Irradiation
Central Nervous System Neoplasms
Drug Therapy
Hematopoietic Stem Cells
Incidence
Thiotepa
Disease-Free Survival
Survival
Consolidation Chemotherapy
Induction Chemotherapy
Poisons
Chemoradiotherapy
Therapeutics
Septic Shock
Liver Diseases
Autopsy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors : A Report From the Children's Oncology Group (CCG-99702). / Nazemi, Kellie J.; Shen, Violet; Finlay, Jonathan L.; Boyett, James; Kocak, Mehmet; Lafond, Deborah; Gardner, Sharon L.; Packer, Roger J.; Nicholson, H. Stacy.

In: Pediatric Blood and Cancer, Vol. 63, No. 9, 01.09.2016, p. 1563-1570.

Research output: Contribution to journalArticle

Nazemi, Kellie J. ; Shen, Violet ; Finlay, Jonathan L. ; Boyett, James ; Kocak, Mehmet ; Lafond, Deborah ; Gardner, Sharon L. ; Packer, Roger J. ; Nicholson, H. Stacy. / High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors : A Report From the Children's Oncology Group (CCG-99702). In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 9. pp. 1563-1570.
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abstract = "Background: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). Procedure: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. Results: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27{\%}) receiving thiotepa Dose Level 1 (150 mg/m2/day × 3 days) and three of 12 (25{\%}) receiving de-escalated Dose Level 0 (100 mg/m2/day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10{\%} and 71 ± 9{\%}, respectively. The 5-year EFS and OS were 46 ± 11{\%} and 50 ± 11{\%}. Conclusions: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.",
author = "Nazemi, {Kellie J.} and Violet Shen and Finlay, {Jonathan L.} and James Boyett and Mehmet Kocak and Deborah Lafond and Gardner, {Sharon L.} and Packer, {Roger J.} and Nicholson, {H. Stacy}",
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T1 - High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors

T2 - A Report From the Children's Oncology Group (CCG-99702)

AU - Nazemi, Kellie J.

AU - Shen, Violet

AU - Finlay, Jonathan L.

AU - Boyett, James

AU - Kocak, Mehmet

AU - Lafond, Deborah

AU - Gardner, Sharon L.

AU - Packer, Roger J.

AU - Nicholson, H. Stacy

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). Procedure: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. Results: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m2/day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m2/day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%. Conclusions: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.

AB - Background: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). Procedure: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. Results: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m2/day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m2/day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%. Conclusions: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.

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