Alkylating agents acute leukemia with

Treatment-induced tumors Since most antineoplastic agents are mutagens, neoplasms (for example, acute nonlymphocytic leukemia) may arise 10 or more years after the original cancer was cured. Treatment-induced neoplasms are especially a problem after therapy with alkylating agents (see p. 387). 

FIGURE 16.12 Hypothetical scheme for the pathogenesis of secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) following cancer chemotherapy with alkylating agents. 

Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001 19 1405-13. 

Two patients with acute promyelocytic leukemia developed therapy-related myelodysplasia 2.0-2.5 years after complete remission and then acute myeloid leukemia both had received anthracyclines (39). In both cases the cytogenetic changes that usually occur after the use of alkylating agents were observed. There has only been one previous similar report after successful therapy with anthracyclines, but these observations suggest that anthracyclines can cause acute myeloid leukemia similar to that caused by alkylating agents. 

These reports and others confirm that even conventional doses of etoposide can be associated with a risk of secondary acute myelogenous leukemia. The risk appears to be related to both the schedule and the cumulative dose, and it can be aggravated by addition of alkylating agents and/or radiotherapy (148,149). 

In summary, ifosfamide, an alkylating agent with anti-neoplastic properties (1.2 g/mVday fV for 5 days), is indicated in the treatment of testicular cancer. In addition, ifosfamide has been used in lung cancer, Hodgkin s and non-Hodgkin s lymphoma, breast cancer, acute and chronic lymphocytic leukemia, ovarian cancer, and sarcomas. 

The leukemic cells have the cytological appearance of acute monocytic or monomyelocytic leukemia. Another distinguishing feature of etoposide-related leukemia is the short time interval between the end of treatment and onset of leukemia (1—3 years), as compared to the 4-5-year interval for secondary leukemias related to alkylating agents, and the absence of a myelodysplastic period preceding leukemia. Patients receiving weekly or twice-weekly doses of etoposide, with cumulative doses above 2000 mg/m, seem to be at higher risk of leukemia. 

Cyclophosphamide is effective against acute leukemia, chronic lymphocytic leukemia and multiple myeloma. In combination with other chemotherapeutic agents it is found to cause radical cure in acute lymphoplastic leukemia in children and also in Burkitt s lymphoma. It has a positive advantage over other alkylating agents because of its activity both parenterally and orally besides its tolerance over prolonged periods in divided doses. 

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