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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.


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.

SUBMITTER: Vrooman LM 

PROVIDER: S-EPMC3736806 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Publications

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 LM   Neuberg Donna S DS   Stevenson Kristen E KE   Asselin Barbara L BL   Athale Uma H UH   Clavell Luis L   Cole Peter D PD   Kelly Kara M KM   Larsen Eric C EC   Laverdière Caroline C   Michon Bruno B   Schorin Marshall M   Schwartz Cindy L CL   Cohen Harvey J HJ   Lipshultz Steven E SE   Silverman Lewis B LB   Sallan Stephen E SE  

European journal of cancer (Oxford, England : 1990) 20110420 9


<h4>Background</h4>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.<h4>Methods</h4>Between 1  ...[more]

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