Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia

Eric S. Sandler, David J. Friedman, Mahmoud M. Mustafa, Naomi J. Winick, W. Paul Bowman, George R. Buchanan

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

BACKGROUND. Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS. The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q21 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS. Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purge autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS. These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

Original languageEnglish (US)
Pages (from-to)1049-1054
Number of pages6
JournalCancer
Volume79
Issue number5
DOIs
StatePublished - Mar 1 1997

Fingerprint

Podophyllotoxin
Acute Myeloid Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transplants
Bone Marrow
perfosfamide
Therapeutics
Remission Induction
Unrelated Donors
Alkylating Agents
Etoposide
HLA Antigens
Bone Marrow Transplantation
Chromosome Aberrations
Siblings
Tissue Donors

Keywords

  • bone marrow transplantation
  • epipodophyllotoxin
  • etoposide
  • secondary leukemia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia. / Sandler, Eric S.; Friedman, David J.; Mustafa, Mahmoud M.; Winick, Naomi J.; Bowman, W. Paul; Buchanan, George R.

In: Cancer, Vol. 79, No. 5, 01.03.1997, p. 1049-1054.

Research output: Contribution to journalArticle

Sandler, Eric S. ; Friedman, David J. ; Mustafa, Mahmoud M. ; Winick, Naomi J. ; Bowman, W. Paul ; Buchanan, George R. / Treatment of children with epipodophyllotoxin-induced secondary acute myeloid leukemia. In: Cancer. 1997 ; Vol. 79, No. 5. pp. 1049-1054.
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abstract = "BACKGROUND. Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS. The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76{\%}) had 11q21 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS. Remission induction was attempted in 16 children, with 13 (81{\%}) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purge autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS. These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.",
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AU - Friedman, David J.

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AU - Buchanan, George R.

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N2 - BACKGROUND. Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS. The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q21 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS. Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purge autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS. These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

AB - BACKGROUND. Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS. The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q21 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS. Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purge autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS. These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.

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