Leukemia risk following Hodgkin's disease: relation to cumulative dose of alkylating agents, treatment with teniposide combinations, number of episodes of chemotherapy, and bone marrow damage.

Leeuwen, Flora E. van; Chorus, A.M.J.; Belt-Dusebout, Alexandra W. van den; Hagenbeek, Anton; Noyon, R.; Kerkhoff, E. H. M. Van; Pinedo, H. M.; Somers, R.

doi:10.1200/jco.1994.12.5.1063

Cited by 174 publications

(77 citation statements)

References 32 publications

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“…We used chicken 6C2 cells for the cytotoxicity studies because avian erythropoiesis is similar to that of mammals, and these erythroprogenitor cells are used to model the development of leukemia (58). Moreover, the use of DNA cross-linkers for cancer therapy is associated with the subsequent development of hemato-pathologies such as leukemia (2,3).…”

Section: Discussionmentioning

confidence: 99%

“…Although these compounds form a variety of cellular lesions, DNA interstrand cross-links are believed to be the most cytotoxic, disrupting normal replication and transcription. This activity is beneficial when directed at cancer cells, yet patients who undergo treatment with cross-linking drugs have elevated risks of developing secondary cancers later in life (2,3). Additionally, occupational exposure to bifunctional alkylating agents can elevate cancer risk for industrial workers.…”

Section: Introductionmentioning

confidence: 99%

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DNA Interstrand Cross-Linking by Epichlorohydrin

Romano

Newman

Zahran

et al. 2007

Chem. Res. Toxicol.

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Epichlorohydrin (ECH), an important industrial chemical, is a bifunctional alkylating agent with the potential to form DNA cross-links. Occupational exposure to this suspect carcinogen leads to chromosomal aberrations, and ECH has been shown previously to undergo reaction with DNA in vivo and in vitro.We used denaturing polyacrylamide gel electrophoresis to monitor the possible formation of interstrand cross-links within DNA oligomers by ECH and the related compound, epibromohydrin (EBH). Although both compounds did indeed form cross-links between deoxyguanosine residues, EBH was a more efficient cross-linker than ECH. The optimal pH for cross-linking also varied, with ECH more efficient at pH 5.0 and EBH more efficient at pH 7.0. Both agents were relatively flexible in the sequences targeted, with comparable efficiencies for 5′-GGC and 5′GC sites. Furthermore, interstrand cross-linking by the two optical isomers of ECH correlated with their relative cytotoxicities, with R-ECH about twice as potent as S-ECH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA Interstrand Cross-Linking by Epichlorohydrin

Romano

Newman

Zahran

et al. 2007

Chem. Res. Toxicol.

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“…Overall, a cumulative risk ranging from 0.8 to 13% has been seen after conventional therapy, with follow-up ranging from 6-20 years. 32,33,[36][37][38][39][40][41][42][43][44] Interestingly, the GHSG found a fairly low incidence of t-AML/MDS (1% at nearly 5 years), likely reflecting a shift away from regimens containing mechlorethimine. 33 In NHL, associations have been identified between secondary AML and conventional doses of chemotherapeutic agents, either alone or in combination with total nodal/body irradiation.…”

Section: Incidence Of T-aml/mds After Conventional Therapymentioning

confidence: 99%

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

Hake

Graubert

Fenske

2006

Bone Marrow Transplant

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Patients who undergo autologous stem cell transplantation (ASCT) for lymphoma have a significant risk of therapy-related acute myeloid leukemia and myelodysplasia (t-AML/MDS). Compared to that seen in other indications such as breast cancer, multiple myeloma or germ cell tumors, there is a substantially increased risk for t-AML/MDS following ASCT for lymphoma. This risk has largely been attributed to the extent of pre-transplant chemotherapy and radiation therapy. In many of the larger series to date, it has not been possible to directly implicate autologous transplantation itself as a risk factor for t-AML/MDS. Although pre-transplant therapy is certainly an important factor in the development of t-AML/MDS, specific components of the autologous transplantation procedure itself may also contribute to the risk of t-AML/MDS. Specifically, priming chemotherapy, total body irradiation, and the extensive cellular proliferation which occurs during engraftment may all play a role in the development of t-AML/MDS. Furthermore, there is an increasing body of evidence that certain inherited polymorphisms in genes governing drug metabolism, DNA repair and leukemogenesis may influence susceptibility to t-AML/MDS. In this paper, we review the evidence implicating the above risk factors for t-AML/MDS, present a potential mechanism for t-AML/ MDS and propose interventions to reduce the rate of t-AML/MDS in lymphoma patients.

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“…1,2 Factors related to the development of secondary AML include a higher age at primary diagnosis, a more advanced disease stage, being within the first year after the completion of initial therapy, number of treatment regimens, and a regimen containing nitrogen mustard and alkylating agents. 3,4 The role of irradiation with regard to the risk of secondary AML is not clear, but a role in increasing the risk for developing a solid tumor has been shown. 2,4 The advantage of allogeneic transplantation for secondary AML is still controversial.…”

mentioning

confidence: 99%

“…3,4 The role of irradiation with regard to the risk of secondary AML is not clear, but a role in increasing the risk for developing a solid tumor has been shown. 2,4 The advantage of allogeneic transplantation for secondary AML is still controversial. Josting et al 1 reported an 8% 2-year overall survival in patients with secondary AML/MDS after HL treatment, a rate that was similar among patients receiving allogeneic transplantation or conventional chemotherapy.…”

mentioning

confidence: 99%