High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors.

Kushner, Brian H.; Heller, G.; Nk, Cheung; Wollner, Norma; Krämer, Kim; Bajorin, Dean F.; Polyak, Tatyana; Meyers, Paul A.

doi:10.1200/jco.1998.16.9.3016

Cited by 70 publications

(52 citation statements)

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“…51,52 Furthermore, the use of DNA-damaging agents, such as radiotherapy and alkylating agents, have been clearly established as independent risk factors for secondary tumors in pediatric patients. 53,54 Although no data on telomere function was provided in these studies, the cytogenetic abnormalities observed might have been caused or aggravated by short or unstable telomeres. In this regard, it has been reported that cisplatin, a nonclassical alkylating agent often used for the treatment of childhood solid tumors, directly targets telomeric DNA.…”

Section: Leukemiamentioning

confidence: 99%

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

et al. 2003

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Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.

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Section: Leukemiamentioning

confidence: 99%

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

et al. 2003

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“…Six months after starting therapy, peripheral monocytosis and cytopenias appeared. The G-banded marrow karyotype obtained 12 months from diagnosis as a routine test was 46,XY,del(11)(q23) [8]͞46,XY [12] (3,8). Seventeen months after starting therapy, the marrow was replaced by FrenchAmerican-British M4 leukemic blasts.…”

Section: Case Reportmentioning

confidence: 99%

“…1). The incidence of leukemia is as high as 20% with intensive alkylating agent regimens for pediatric solid tumors (2,3). The incidence of epipodophyllotoxin-related cases is 2-3% (4).…”

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confidence: 99%

Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors

Megonigal

Cheung

Rappaport

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

104

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Leukemias with MLL gene translocations are a complication of primary cancer treatment with DNA topoisomerase II inhibitors. How early translocations appear during primary cancer treatment has not been investigated. We tracked the leukemic clone with an MLL gene translocation during neuroblastoma therapy in a child who developed acute myeloid leukemia. The karyotype of the leukemic clone showed del(11)(q23). We used panhandle PCRbased methods to isolate the breakpoint junction involving MLL and an unknown partner gene. Marrow DNA from neuroblastoma diagnosis and DNA and RNA from serial preleukemic marrows were examined for the translocation. The karyotypic del(11)(q23) was a cryptic t(11;17). GAS7, a growth arrest-specific gene at chromosome band 17p13, was the partner gene of MLL. Two different MLL-GAS7 fusion transcripts were expressed. The translocation was already detectable by 1.5 months after the start of neuroblastoma treatment. The translocation was not detectable in the marrow at neuroblastoma diagnosis or in peripheral blood lymphocyte DNAs of six normal subjects. GAS7 is a new partner gene of MLL in treatment-related acute myeloid leukemia. MLL gene translocations can be present early during anticancer treatment at low cumulative doses of DNA topoisomerase II inhibitors. Although MLL has many partner genes and most have not been characterized, panhandle PCR strategies afford new means for detecting MLL gene translocations early during therapy when the partner gene is unknown.

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“…6,7 Childhood cancer survivors can also develop AML or MDS after treatment with growth factors (GFs), in combination with etoposide, anthracyclines, and radiotherapy. However, it is difficult to distinguish the contribution of GF versus intensified therapy and the effect of intensity 8 or cumulative doses of chemotherapy 9,10 in the development of secondary hematological malignancies.…”

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confidence: 99%

Secondary hematopoietic malignancies in survivors of childhood cancer

Rihani

Bazzeh

Faqih

et al. 2010

Cancer

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BACKGROUND: Studying secondary hematological malignancies in a large cohort of patients can help predict risks and trends associated with current therapies. METHODS: The authors analyzed data from the Surveillance, Epidemiology, and End Resultsecondary 9 (SEER-9) database on patients with a primary malignancy (diagnosed before the age of 20 years) between 1973 and 2005 who developed a secondary hematological malignancy. Primary cancer and histological subtype, incidence, risk factors, outcomes, and changes in risk patterns of secondary hematological malignancies were analyzed for 1973 to 1985, 1986 to 1995, and 1996 to 2005. Standardized incidence ratios (SIRs) of observed to expected cancers were calculated. RESULTS: Of 34,867 patients with a histology-confirmed primary malignancy, 111 developed secondary hematological malignancies (median, 44 months). Lymphoma was the commonest primary cancer (n ¼ 47). The main histological subtype of secondary hematological malignancy was acute myeloid leukemia (AML) (49%), which had the shortest median latency time and the worst 5-year survival (18% AE 5.3%; P ¼.044). Secondary Hodgkin lymphoma had the best 5-year survival (83% AE 15%). The 5-year overall survival for patients with secondary hematological malignancies was 31% AE 4.7%. The risk of secondary AML steadily increased from 1986 to 2005, whereas SIRs for acute lymphoblastic leukemia did not change over time. Non-Hodgkin lymphoma, the second most common secondary hematological malignancy, occurred at a median of 112 months, and its risk steadily increased over time periods. CONCLUSIONS: Childhood cancer survivors are at increased risk of developing secondary hematological malignancies, particularly secondary AML. This risk has continued to rise even in recent years, emphasizing the need to study other factors contributing to secondary hematological malignancies and closely monitor these patients. Cancer 2010;116:4385-94.

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High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors.

Cited by 70 publications

References 0 publications

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors

Secondary hematopoietic malignancies in survivors of childhood cancer

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