Therapy‐related acute myeloid leukemia following treatment for cancer in childhood: A population‐based registry study

Brown, Catherine; Youlden, Danny R.; Aitken, Joanne F.; Moore, Andrew S.

doi:10.1002/pbc.27410

Cited by 15 publications

(16 citation statements)

References 23 publications

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“…Radiotherapy is the only risk factor for subsequent development of these two solid cancer types supported by strong clinical evidence . Chemotherapy of childhood cancer increases the risk of a second cancer diagnosis, particularly of haematological malignancies, the most common form being therapy‐related acute myeloid leukaemia . About 80% of therapy‐related acute myeloid leukaemias and 30% of all second primary cancers in our cohort were diagnosed within 5 years of the initial cancer diagnosis, which indicates the importance of estimating second primary cancer risk from close to the first diagnosis.…”

Section: Discussionmentioning

confidence: 60%

“…20 Chemotherapy of childhood cancer increases the risk of a second cancer diagnosis, particularly of haematological malignancies, 21 the most common form being therapy-related acute myeloid leukaemia. 22 About 80% of therapy-related acute myeloid leukaemias and 30% of all second primary cancers in our cohort were diagnosed within 5 years of the initial cancer diagnosis, which indicates the importance of estimating second primary cancer risk from close to the first diagnosis. While it is possible that lifestyle and environmental factors also contribute to the increased risk of second cancers, the health behaviour of people who had childhood cancer is similar to that of their peers, apart from their generally being less physically active.…”

Section: Discussionmentioning

confidence: 77%

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Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population‐based study

Youlden

Baade

Green

et al. 2019

Medical Journal of Australia

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Objective To investigate the incidence of second primary cancers in people diagnosed with cancer during childhood. Design, setting Retrospective, population‐based study; analysis of Australian Childhood Cancer Registry data. Participants People alive at least two months after being diagnosed before the age of 15 years with a primary cancer, 1983–2013, followed until 31 December 2015 (2–33 years' follow‐up). Main outcome measures Risks of second primary cancer compared with the general population, expressed as standardised incidence ratios (SIRs). Results Among 18 230 people diagnosed with cancer during childhood, 388 (2%) were later diagnosed with second primary cancers; the estimated 30‐year cumulative incidence of second cancers was 4.4% (95% CI, 3.8–5.0%). The risk of a new primary cancer was five times as high as for the general population (SIR, 5.13; 95% CI, 4.65–5.67). Relative risk of a second primary cancer was greatest for people who had childhood rhabdomyosarcoma (SIR, 19.9; 95% CI, 14.4–27.6). Relative risk was particularly high for children who had undergone both chemotherapy and radiotherapy (SIR, 9.80; 95% CI, 8.35–11.5). Relative risk peaked during the 5 years following the first diagnosis (2 to less than 5 years: SIR, 10.3; 95% CI, 8.20–13.0), but was still significant at 20–33 years (SIR, 2.58; 95% CI, 2.02–3.30). The most frequent second primary cancers were thyroid carcinomas (65 of 388, 17%) and acute myeloid leukaemias (57, 15%). Conclusions Survivors of childhood cancer remain at increased risk of a second primary cancer well into adulthood. As the late effects of cancer treatment probably contribute to this risk, treatments need to be refined and their toxicity reduced, without reducing their benefit for survival.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 77%

Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population‐based study

Youlden

Baade

Green

et al. 2019

Medical Journal of Australia

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confidence: 99%

“…A lthough the therapeutic regimens for pediatric cancer have improved with a resultant overall decrease in the incidence of tMN in children [1][2][3][4] , approximately 0.5-1.0% of children continue to develop tMN after therapy for hematological, solid, and CNS malignancies 2 . Children with tMN have a worse prognosis compared to de novo MDS/AML, with 5-year survival rates of 6-11% if not treated with hematopoietic cell transplant (HCT) 1,2 . While much effort has focused on tMN in adults [5][6][7][8][9] , a complete understanding of the pathogenesis of tMN in children is lacking despite well-described associations with alkylating agents (e.g., cyclophosphamide), topoisomerase II inhibitors (e.g., the epipodophyllotoxins etoposide and teniposide), radiation therapy, and HCT [10][11][12][13][14] .…”

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confidence: 99%

The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms

Schwartz

Kamens

et al. 2021

Nat Commun

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Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.

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“…In a US study, sex disparities in survival among adults with AML reduced over the 1973-2014 period [29]. The opposite was seen in patients diagnosed with t-AML at less than 25 years of age, where the 5-year all-cause survival ranged from 49.8% in women to 23.1% in men [30]. Molecular, genetic and other biological disease features, patient clinical profiles or lifestyle trajectories might explain this.…”

Section: Discussionmentioning

confidence: 99%

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM

Mounier

Romain

Callanan

et al. 2021

JCM

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With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. When cure assumption was acceptable, the flexible cure model was used to estimate P, TTC and MedS for the uncured patients. The 5-year NS varied from 68% to 9% in men and from 77% to 11% in women in acute promyelocytic leukemia (AML-APL) and in therapy-related AML (t-AML), respectively. Major age-differenced survival was observed for patients with a diagnosis of AML with recurrent cytogenetic abnormalities. A poorer survival in younger patients was found in t-AML and AML with minimal differentiation. An atypical survival profile was found for acute myelomonocytic leukemia and AML without maturation in both sexes and for AML not otherwise specified (only for men) according to age, with a better prognosis for middle-aged compared to younger patients. Sex disparity regarding survival was observed in younger patients with t-AML diagnosed at 25 years of age (+28% at 5 years in men compared to women) and in AML with minimal differentiation (+23% at 5 years in women compared to men). All AML subtypes included an age group for which the assumption of cure was acceptable, although P varied from 90% in younger women with AML-APL to 3% in older men with acute monoblastic and monocytic leukemia. Increased P was associated with shorter TTC. A sizeable proportion of AML patients do not achieve cure, and MedS for these did not exceed 23 months. We identify AML subsets where cure assumption is negative, thus pointing to priority areas for future research efforts.

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Therapy‐related acute myeloid leukemia following treatment for cancer in childhood: A population‐based registry study

Abstract: Although rare, t-AML is an important potential late effect of childhood cancer therapy. Prognosis is generally poor, with HSCT offering some survival benefit.

Cited by 15 publications

References 23 publications

Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population‐based study

Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population‐based study

The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM

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