The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: A report from the Dana-Farber Cancer Institute ALL Consortium

Lynda M. Vrooman, Donna S. Neuberg, Kristen E. Stevenson, Barbara L. Asselin, Uma H. Athale, Luis Clavell, Peter D. Cole, Kara M. Kelly, Eric C. Larsen, Caroline Laverdire, Bruno Michon, Marshall Schorin, Cindy L. Schwartz, Harvey J. Cohen, Steven E Lipshultz, Lewis B. Silverman, Stephen E. Sallan

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Abstract

Background: Dexrazoxane reduces the risk of anthracycline-related cardiotoxicity. In a study of children with Hodgkin lymphoma, the addition of dexrazoxane may have been associated with a higher risk for developing second malignant neoplasms (SMNs) including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). We determined the incidence of SMNs in children and adolescents with acute lymphoblastic leukaemia (ALL) who were treated with dexrazoxane. Methods: Between 1996 and 2010, the Dana-Faber Cancer Institute ALL Consortium conducted three consecutive multicentre trials for children with newly diagnosed ALL. In the first (1996-2000), high risk patients were randomly assigned to receive doxorubicin (30 mg/m 2/dose, cumulative dose 300 mg/m 2) preceded by dexrazoxane (300 mg/m 2/dose, 10 doses), or the same dose of doxorubicin without dexrazoxane, during induction and intensification phases. In subsequent trials (2000-2005 and 2005-2010), all high risk and very high risk patients received doxorubicin preceded by dexrazoxane. Cases of SMNs were collected prospectively and were pooled for analysis. The frequency and 5-year cumulative incidence (CI) of SMNs were determined for patients who had received dexrazoxane. Findings: Among 553 patients treated with dexrazoxane (1996-2000, N = 101; 2000-2005, N = 196; and 2005-2010, N = 256), the number of SMNs observed by protocol was 0 (median follow-up 9.6 years), 0 (median follow-up 5.2 years), and 1 (median follow-up 2.1 years). The only SMN was a case of AML, which developed in a patient with MLL-rearranged ALL 2.14 years after initial diagnosis. The overall 5-year CI of SMNs for all 553 patients was 0.24 ± 0.24%. Interpretation: In a large population of children with high risk ALL who received dexrazoxane as a cardioprotectant drug, the occurrence of secondary AML was a rare event.

Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
JournalEuropean Journal of Cancer
Volume47
Issue number9
DOIs
StatePublished - Jun 1 2011

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Dexrazoxane
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Second Primary Neoplasms
Incidence
Neoplasms
Doxorubicin
Anthracyclines
Myelodysplastic Syndromes
Hodgkin Disease
Multicenter Studies

Keywords

  • Acute lymphoblastic leukemia
  • Childhood leukemia
  • Dexrazoxane
  • Second malignant neoplasm
  • Secondary acute myelogenous leukemia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia : A report from the Dana-Farber Cancer Institute ALL Consortium. / Vrooman, Lynda M.; Neuberg, Donna S.; Stevenson, Kristen E.; Asselin, Barbara L.; Athale, Uma H.; Clavell, Luis; Cole, Peter D.; Kelly, Kara M.; Larsen, Eric C.; Laverdire, Caroline; Michon, Bruno; Schorin, Marshall; Schwartz, Cindy L.; Cohen, Harvey J.; Lipshultz, Steven E; Silverman, Lewis B.; Sallan, Stephen E.

In: European Journal of Cancer, Vol. 47, No. 9, 01.06.2011, p. 1373-1379.

Research output: Contribution to journalArticle

Vrooman, LM, Neuberg, DS, Stevenson, KE, Asselin, BL, Athale, UH, Clavell, L, Cole, PD, Kelly, KM, Larsen, EC, Laverdire, C, Michon, B, Schorin, M, Schwartz, CL, Cohen, HJ, Lipshultz, SE, Silverman, LB & Sallan, SE 2011, 'The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: A report from the Dana-Farber Cancer Institute ALL Consortium', European Journal of Cancer, vol. 47, no. 9, pp. 1373-1379. https://doi.org/10.1016/j.ejca.2011.03.022
Vrooman, Lynda M. ; Neuberg, Donna S. ; Stevenson, Kristen E. ; Asselin, Barbara L. ; Athale, Uma H. ; Clavell, Luis ; Cole, Peter D. ; Kelly, Kara M. ; Larsen, Eric C. ; Laverdire, Caroline ; Michon, Bruno ; Schorin, Marshall ; Schwartz, Cindy L. ; Cohen, Harvey J. ; Lipshultz, Steven E ; Silverman, Lewis B. ; Sallan, Stephen E. / The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia : A report from the Dana-Farber Cancer Institute ALL Consortium. In: European Journal of Cancer. 2011 ; Vol. 47, No. 9. pp. 1373-1379.
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T2 - A report from the Dana-Farber Cancer Institute ALL Consortium

AU - Vrooman, Lynda M.

AU - Neuberg, Donna S.

AU - Stevenson, Kristen E.

AU - Asselin, Barbara L.

AU - Athale, Uma H.

AU - Clavell, Luis

AU - Cole, Peter D.

AU - Kelly, Kara M.

AU - Larsen, Eric C.

AU - Laverdire, Caroline

AU - Michon, Bruno

AU - Schorin, Marshall

AU - Schwartz, Cindy L.

AU - Cohen, Harvey J.

AU - Lipshultz, Steven E

AU - Silverman, Lewis B.

AU - Sallan, Stephen E.

PY - 2011/6/1

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N2 - Background: Dexrazoxane reduces the risk of anthracycline-related cardiotoxicity. In a study of children with Hodgkin lymphoma, the addition of dexrazoxane may have been associated with a higher risk for developing second malignant neoplasms (SMNs) including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). We determined the incidence of SMNs in children and adolescents with acute lymphoblastic leukaemia (ALL) who were treated with dexrazoxane. Methods: Between 1996 and 2010, the Dana-Faber Cancer Institute ALL Consortium conducted three consecutive multicentre trials for children with newly diagnosed ALL. In the first (1996-2000), high risk patients were randomly assigned to receive doxorubicin (30 mg/m 2/dose, cumulative dose 300 mg/m 2) preceded by dexrazoxane (300 mg/m 2/dose, 10 doses), or the same dose of doxorubicin without dexrazoxane, during induction and intensification phases. In subsequent trials (2000-2005 and 2005-2010), all high risk and very high risk patients received doxorubicin preceded by dexrazoxane. Cases of SMNs were collected prospectively and were pooled for analysis. The frequency and 5-year cumulative incidence (CI) of SMNs were determined for patients who had received dexrazoxane. Findings: Among 553 patients treated with dexrazoxane (1996-2000, N = 101; 2000-2005, N = 196; and 2005-2010, N = 256), the number of SMNs observed by protocol was 0 (median follow-up 9.6 years), 0 (median follow-up 5.2 years), and 1 (median follow-up 2.1 years). The only SMN was a case of AML, which developed in a patient with MLL-rearranged ALL 2.14 years after initial diagnosis. The overall 5-year CI of SMNs for all 553 patients was 0.24 ± 0.24%. Interpretation: In a large population of children with high risk ALL who received dexrazoxane as a cardioprotectant drug, the occurrence of secondary AML was a rare event.

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