Alkylating agents as leukemogens in multiple myeloma

Karchmer, Richard K.; Amare, Mammo; Larsen, William E.; Mallouk, Alexander G.; Caldwell, Glyn G.

doi:10.1002/1097-0142(197404)33:4<1103::aid-cncr2820330432>3.0.co;2-s

Cited by 63 publications

(11 citation statements)

References 24 publications

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“…Individuals developing ANLL after cyclophosphamide treatment for nonmalignant disease include six arthritis patients (89,90,92,108), three patients with chronic renal disease (109), and one patient each with fibromatosis (110), Sjogren's syndrome (111), Wegener's granulomatosis (112), and macroglobulinemia (113). Moreover, ANLL has been reported to be the terminal event in five patients with multiple myeloma (71,72,113,114), two ovarian carcinoma patients (58), and four women with breast cancer (115). Cyclophosphamide has well-demonstrated carcinogenicity in rodents (40,74,75,116), and a study of its leukemogenic potential in nonhuman primates was recently initiated in this laboratory.…”

Section: Cyclophosphamidementioning

confidence: 99%

Chemically induced leukemia in humans.

Adamson¹,

Seiber²

1981

Environ Health Perspect

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The human population may be exposed to potentially leukemogenic agents, either in the form of drugs and food additives or as environmental contaminants and pollutants. However, in spite of the large number and diversity of these chemicals, only a few have been implicated as human leukemogens. One such agent is benzene, a known bone marrow depressant. A number of case reports have associated chronic exposure to this agent with the development of acute leukemia, as have several epidemiologic surveys. Treatment with various antitumor agents, including procarbazine, melphalan, thio-TEPA, chlorambucil, and cyclophosphamide, has also been associated with the development of acute leukemia. In addition, chloramphenicol and phenylbutazone have been implicated as human leukemogens, but the association between exposure to these two agents and acute leukemia appears at present to be weaker than it is for benzene and antitumor agent exposure. Despite such associations between exposure to chemicals and acute leukemia, several important problems exist with regard to implicating specific agents in the development of this neoplasm in man, including the paucity of animal models for chemically induced leukemia, and the frequent necessity to rely on single case reports or clusters of cases in which chemical exposures are associated with acute leukemia. Future efforts should be directed at performing properly designed and well executed epidemiologic studies, and at developing new in vitro and in vivo models for the study of this neoplasm.

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Section: Cyclophosphamidementioning

confidence: 99%

Chemically induced leukemia in humans.

Adamson¹,

Seiber²

1981

Environ Health Perspect

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“…It is well established that radiotherapy1,2 and chemotherapy (specifically alkylating agents3–5 and topoisomerase II inhibitors6) may lead to the development of therapy-related myelodysplastic syndrome or AML (tMDS/AML) 7. Patients with breast cancer who receive adjuvant therapy most often receive one or several of the above treatments.…”

Section: Introductionmentioning

confidence: 99%

Outcome of allo-SCT for women with MDS or AML occurring after breast cancer therapy

Armand

Kim

Mayer

et al. 2010

Bone Marrow Transplant

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Women with breast cancer who receive adjuvant therapy are at risk for developing therapy-related myelodysplastic syndrome (MDS) or AML (tMDS/AML). Patients with tMDS/AML are often referred for consideration of allogeneic hematopoietic SCT (HSCT). However, the outcomes of HSCT in such patients have not been well described. We report a retrospective study of all women who were treated with HSCT for MDS or AML at our institution between 1991 and 2008. We compared the transplantation outcomes for 24 women with a history of breast cancer with those for 271 women with de novo disease. Three-year OS and disease-free survival (DFS) for patients with a history of breast cancer were 41 and 45%, respectively. The cumulative incidences of tMDS/ AML relapse and non-relapse mortality (NRM) were 38 and 17%, respectively. Those outcomes were very similar to those of patients with de novo disease. In multivariable analyses, a history of breast cancer had no impact on OS, DFS, relapse or NRM. A significant proportion of women with tAML/MDS after breast cancer treatment experience DFS after HSCT, similar to that of patients with de novo MDS or AML. This justifies consideration of HSCT for selected patients in this setting.

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“…Since the etiology of endometriosis has not yet been clearly elucidated, the melphalan treated-animal may serve as an important experimental model for the human disease. 33),34) …”

Section: Discussionmentioning

confidence: 99%

Chemical carcinogenesis studies in nonhuman primates

Takayama

Thorgeirsson²,

Adamson³

2008

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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This review covers chemical carcinogenesis studies in nonhuman primates performed by the National Cancer Institute, USA, to provide hitherto unavailable information on their susceptibility to compounds producing carcinogenic effects in rodents. From autopsy records of 401 breeders and untreated controls, incidences of spontaneous malignant tumors were found to be relatively low in cynomolgus (1.9%) and rhesus monkeys (3.8%), but higher in African green monkeys (8%). Various chemical compounds, and in particular 6 antineoplastic agents, 13 food-related compounds including additives and contaminants, 1 pesticide, 5 N-nitroso compounds, 3 heterocyclic amines, and 7 ''classical'' rodent carcinogens, were tested during the 34 years period, generally at doses 10$40 times the estimated human exposure. Results were inconclusive in many cases but unequivocal carcinogenicity was demonstrated for IQ, procarbazine, methylnitrosourea and diethylnitrosamine. Furthermore, negative findings for saccharine and cyclamate were in line with results in other species. Thus susceptibility to carcinogens is at least partly shared by nonhuman primates and rodents.

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Alkylating agents as leukemogens in multiple myeloma

Cited by 63 publications

References 24 publications

Chemically induced leukemia in humans.

Chemically induced leukemia in humans.

Outcome of allo-SCT for women with MDS or AML occurring after breast cancer therapy

Chemical carcinogenesis studies in nonhuman primates

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