Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.

Hawkins, Mike; Wilson, Lisa; Stovall, Marilyn; Marsden, H. B.; Potok, M H N; Kingston, J E; Chessells, J M

doi:10.1136/bmj.304.6832.951

Cited by 213 publications

(138 citation statements)

References 36 publications

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“…As to the pathogenetic role of previous treatments, the importance of chemotherapy including topoisomerase II inhibitors has been reported by several authors. [6][7][8][9][10][11][12] These drugs had been employed for the treatment of PMs in 11 (22%) of our patients. A high proportion of patients in our study (53%) had previously been treated with radiotherapy (alone or combined with chemotherapy) for their PMs.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] For example, consistent karyotypic changes are reported in AL-st patients receiving alkylating or topoisomerase II inhibitors for their PM. [4][5][6][7][8][9][10][11] In addition, a significant fraction of AL-st's develop in patients who had previously received radiotherapy with or without chemotherapy. Together, these AL-st's are also referred to as therapy-related ALs.…”

Section: Introductionmentioning

confidence: 99%

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Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience

Pulsoni

2002

Blood

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We analyzed the clinicobiological features and treatment outcome of a series of acute promyelocytic leukemias (APLs) occurring as a second tumor (APL-st's, n ‫؍‬ 51) and compared these with a large group of de novo APL cases (n ‫؍‬ 641), both observed by the Italian cooperative group GIMEMA. In the APL-st group, 37 patients had received radiotherapy and/or chemotherapy for their primary malignancy (PM), while 14 had been treated by surgery alone. Compared with de novo APL patients, APL-st patients were characterized by a predominance of females (P < .003), higher median age (P < .05), and worse performance status (P < .005).The median time elapsed between PM and APL-st was 36 months, with a longer latency for patients treated with surgery alone. No significant differences were found with regard to karyotypic lesions or type of promyelocytic leukemia/retinoic acid receptor ␣ (PML/RAR␣) fusion in the 2 cohorts. A high prevalence of PMs of the reproductive system was observed among the female APL-st population (24 [71%] of 34 patients in this group had suffered from breast, uterine, or ovarian cancer). Thirty-one APL-st and 641 de novo APL patients received homogeneous APL therapy according to the alltrans retinoic acid (ATRA) and idarubicin regimen (the AIDA regimen). The complete remission (CR), 4-year event-free survival (EFS), and 4-year overall survival (OS) rates were 97% and 93%, 65% and 68%, and 85% and 78% in the APL-st and de novo APL groups, respectively. In spite of important clinical differences (older age and poorer performance status), the APL-st group responded as well as the de novo APL group to upfront ATRA plus chemotherapy, probably reflecting genetic similarity. (Blood. 2002; 100:1972-1976

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience

Pulsoni

2002

Blood

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“…Secondary leukaemias occurring after chemotherapy alone (Curtis et al, 1992;Hawkins et al, 1992) and their radiotherapyinduced counterparts, as well as those occurring after a combination of radiotherapy and chemotherapy (Tucher et al, 1987;Andrieu et al, 1990;Henry Amar and Dietrich, 1993;Olsen et al, 1993) appear to exhibit a wave-like temporal pattern, with most of the excess occurring within 10 years of the first cancer. Their temporal pattern of onset is not substantially different from that of leukaemias following irradiation for a non-malignant disease or for a non-medical reason (UNSCEAR, 1994).…”

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confidence: 99%

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment

Hawkins²,

et al. 1999

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SummaryThe variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.

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“…17 The risk of secondary acute myelogenous leukemia is related to the cumulative dose of alkylating agents or treatment exposures, including topoisomerase II inhibitors, like epipodophyllotoxins and anthracyclines, whereas secondary solid tumors appear to be associated largely with radiation therapy; concurrent alkylating agent chemotherapy may increase the risk of secondary pulmonary and gastrointestinal tumors. [17][18][19][20][21][22][23][24][25][26] Finally, breast cancer risk after Hodgkin disease has been observed almost exclusively in female survivors. 20 -26 Treatment with higher cumulative radiation doses and treatment during puberty enhance this risk.…”

Section: Primary Interventions In the Care Continuummentioning

confidence: 99%

A model for care across the cancer continuum

Hudson¹

2005

Cancer

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With contemporary therapy, the majority of children and adolescents who are diagnosed with cancer will be cured. However, curative therapy predisposes individuals to adverse health outcomes that affect the long-term survivor's quality of life and increase the risk of early mortality. Recognition of the adverse effects of cancer treatment on growth and development, vital organ function, fertility and reproduction, and secondary carcinogenesis has been the stimulus for the development of risk-adapted treatment approaches for pediatric malignancies. Because the consequences of these therapeutic modifications may not manifest for many years, long-term follow-up is required to accurately define new or changing patterns of adverse health outcomes, appropriate screening approaches, and ultimately, risk-reducing interventions. Identification of vulnerable survivors is essential to provide timely interventions to detect, ameliorate, reduce, or prevent cancer-related sequelae. This process is challenging, because risk factors constantly are evolving as cancer therapies are modified and as survivors age. Aging also disrupts the continuity of after-cancer care, as adolescent and young adult survivors graduate from pediatric oncology practices to community medical providers who are largely unfamiliar with cancer-related health risks. Health outcomes research objectives that target cancer survivors must adapt as cancer therapies evolve and as new risk factors for cancer-related morbidity emerge. Prospectively using a multidimensional, comprehensive approach that considers host-related, cancer-related, genetic, and lifestyle factors in combination with results from focused medical and behavioral evaluations obtained from cancer survivors who participate in long-term follow-up programs provides an optimal method of defining high-risk profiles for adverse health outcomes across the age spectrum.

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Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.

Cited by 213 publications

References 36 publications

Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience

Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment

A model for care across the cancer continuum

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