TY - JOUR
T1 - The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia
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.
N1 - Funding Information:
This work was supported in part by Grant 5 P01CA068484 from the National Cancer Institute of the National Institutes of Health (Bethesda, MD) and the Michael Garil Fund.
PY - 2011/6
Y1 - 2011/6
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.
AB - 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.
KW - Acute lymphoblastic leukemia
KW - Childhood leukemia
KW - Dexrazoxane
KW - Second malignant neoplasm
KW - Secondary acute myelogenous leukemia
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UR - http://www.scopus.com/inward/citedby.url?scp=79957557043&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2011.03.022
DO - 10.1016/j.ejca.2011.03.022
M3 - Article
C2 - 21514146
AN - SCOPUS:79957557043
SN - 0959-8049
VL - 47
SP - 1373
EP - 1379
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 9
ER -
