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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. Eur J Cancer 2011 Jun;47(9):1373-9

Date

04/26/2011

Pubmed ID

21514146

Pubmed Central ID

PMC3736806

DOI

10.1016/j.ejca.2011.03.022

Scopus ID

2-s2.0-79957557043   85 Citations

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 (30mg/m(2)/dose, cumulative dose 300mg/m(2)) preceded by dexrazoxane (300mg/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 9.6years), 0 (median follow-up 5.2years), and 1 (median follow-up 2.1years). The only SMN was a case of AML, which developed in a patient with MLL-rearranged ALL 2.14years 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.

Author List

Vrooman LM, Neuberg DS, Stevenson KE, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly KM, Larsen EC, Laverdière C, Michon B, Schorin M, Schwartz CL, Cohen HJ, Lipshultz SE, Silverman LB, Sallan SE

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Antineoplastic Agents
Cardiotonic Agents
Child
Child, Preschool
Female
Humans
Incidence
Infant
Infant, Newborn
Leukemia, Myeloid, Acute
Male
Neoplasms, Second Primary
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Razoxane
Risk
Time Factors
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab