Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma

Alissa Martin, Jennifer Schneiderman, Irene B. Helenowski, Elaine R Morgan, Kimberley Dilley, Karina Danner-Koptik, Mohamad Hatahet, Hiroyuki Shimada, Susan L. Cohn, Morris Kletzel, Nobuko Hijiya*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. Methods: We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n=12) and Chicago Pilot 2 (CP2; n=75). Results: The 15-year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1-45.0%). The 10- and 15-year cumulative incidence of SMN was 16.5% (95%CI, 7.2-38.0%) and 34.2% (95%CI, 18.6-63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n=2 in CP1 and n=8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. Conclusion: A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350-1356.

Original languageEnglish (US)
Pages (from-to)1350-1356
Number of pages7
JournalPediatric Blood and Cancer
Volume61
Issue number8
DOIs
StatePublished - Jan 1 2014

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Neuroblastoma
Stem Cells
Drug Therapy
Neoplasms
Hematologic Neoplasms
Confidence Intervals
Survival Rate
Consolidation Chemotherapy
Podophyllotoxin
Chondrosarcoma
Induction Chemotherapy
Alkylating Agents
Myelodysplastic Syndromes
Incidence
Clinical Protocols
Acute Myeloid Leukemia
Survivors
Hepatocellular Carcinoma
Adenocarcinoma
Survival

Keywords

  • AML
  • Alkylating agents
  • Epipodophyllotoxins
  • MDS
  • Neuroblastoma
  • Second malignant neoplasm

ASJC Scopus subject areas

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

Cite this

Martin, Alissa ; Schneiderman, Jennifer ; Helenowski, Irene B. ; Morgan, Elaine R ; Dilley, Kimberley ; Danner-Koptik, Karina ; Hatahet, Mohamad ; Shimada, Hiroyuki ; Cohn, Susan L. ; Kletzel, Morris ; Hijiya, Nobuko. / Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma. In: Pediatric Blood and Cancer. 2014 ; Vol. 61, No. 8. pp. 1350-1356.
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abstract = "Background: Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. Methods: We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n=12) and Chicago Pilot 2 (CP2; n=75). Results: The 15-year overall survival rate for all 87 patients was 33.9{\%} (95{\%} confidence interval [CI], 23.1-45.0{\%}). The 10- and 15-year cumulative incidence of SMN was 16.5{\%} (95{\%}CI, 7.2-38.0{\%}) and 34.2{\%} (95{\%}CI, 18.6-63.1{\%}), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n=2 in CP1 and n=8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. Conclusion: A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350-1356.",
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Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma. / Martin, Alissa; Schneiderman, Jennifer; Helenowski, Irene B.; Morgan, Elaine R; Dilley, Kimberley; Danner-Koptik, Karina; Hatahet, Mohamad; Shimada, Hiroyuki; Cohn, Susan L.; Kletzel, Morris; Hijiya, Nobuko.

In: Pediatric Blood and Cancer, Vol. 61, No. 8, 01.01.2014, p. 1350-1356.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma

AU - Martin, Alissa

AU - Schneiderman, Jennifer

AU - Helenowski, Irene B.

AU - Morgan, Elaine R

AU - Dilley, Kimberley

AU - Danner-Koptik, Karina

AU - Hatahet, Mohamad

AU - Shimada, Hiroyuki

AU - Cohn, Susan L.

AU - Kletzel, Morris

AU - Hijiya, Nobuko

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. Methods: We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n=12) and Chicago Pilot 2 (CP2; n=75). Results: The 15-year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1-45.0%). The 10- and 15-year cumulative incidence of SMN was 16.5% (95%CI, 7.2-38.0%) and 34.2% (95%CI, 18.6-63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n=2 in CP1 and n=8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. Conclusion: A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350-1356.

AB - Background: Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. Methods: We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n=12) and Chicago Pilot 2 (CP2; n=75). Results: The 15-year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1-45.0%). The 10- and 15-year cumulative incidence of SMN was 16.5% (95%CI, 7.2-38.0%) and 34.2% (95%CI, 18.6-63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n=2 in CP1 and n=8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. Conclusion: A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350-1356.

KW - AML

KW - Alkylating agents

KW - Epipodophyllotoxins

KW - MDS

KW - Neuroblastoma

KW - Second malignant neoplasm

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