Blood cancers

Childhood cancer survivors at 50-fold increased risk of therapy-related AML

Childhood cancer survivors treated with chemotherapy and or radiotherapy are at an almost fifty-fold increased risk of AML compared to those without cancer, the first study of its kind reports.

While the absolute risk of therapy-related AML (t-AML) was small, the finding was pertinent given that AML was one of the most commonly diagnosed malignancies among childhood cancers, noted the authors from Queensland in a paper published in Paediatric Blood and Cancer.

Their analysis of 11,753 patients recorded in the Australian Childhood Cancer Registry between 1983 and 2014 found that 0.5% of the cohort (n= 58) were diagnosed with AML related to chemotherapy and or radiotherapy treatment.

These patients had an almost 50-fold standard incidence ratio (SIR 45.6) of t-AML compared to the general population, with most cases (N=45) diagnosed within five years of their primary cancer.

The number of males diagnosed with t-AML was almost double the amount of females (39 vs 19) but the authors noted that the gender disparity was not statistically significant, most likely due to the small number of cases in the cohort.

The most common original cancers were acute  lymphoid leukaemia (n=21), Ewing bone tumours (n=6) and rhabdomyosarcoma (n=6).

Therapy related AML was linked to a poor prognosis, with a five-year observed survival for t-AML of 31% compared to recent estimates of 77% for five-year relative survival following childhood AML in Australia.

However haematopoietic stem cell transplant (HSCT) conferred a survival advantage, the authors found, illustrated by a five-year observed survival of 52% for the children who received a stem cell transplant compared to 6% who did not receive a transplant.

The authors from the Oncology Services Group, Children’s Health Queensland and Cancer Council Queensland, cautioned that they had not been able to rule out potential confounding factors associated with the use of HSCT.

“Perhaps the most notable is our inability to report on why certain paediatric patients were offered HSCT and others were not. For example, if the reason patients were not offered HSCT was because they were too unwell or they died before it was possible to perform the procedure, then our finding may simply represent their pre-existing poor condition other than the effectiveness of HSCT as a therapy,” they wrote.

Nevertheless, together with the evidence from other studies, the research team said their findings showed that therapy for t-AML in children should be with the aim of achieving remission and bridging the patients to HSCT.

“Given the high mortality associated with t-AML and with our study identifying HSCT as an effective therapy it seems prudent that children should be prepared for HSCT as soon as possible after a diagnosis of t-AML to increase their chance of survival,” the researchers said.

Advances in HSCT techniques that increase donor options, such as haploidentical transplantation, may improve outcomes for those who respond to induction therapy and can undergo the procedure,” they added.

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