YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==MYELODYSPLASIA== 16 AUTHOR Bolwell BJ AUTHOR Cassileth PA AUTHOR Gale RP TITLE Low dose cytosine arabinoside in myelodysplasia and acute myelogenous leukemia: a review. SOURCE Leukemia; VOL 1, ISS 8, 1987, P575-9 (REF: 20) ABSTRACT We analyzed clinical trials of low dose cytosine arabinoside (LDARA-C) in 324 patients with acute myelogenous leukemia (AML) and 129 patients with myelodysplasia (MDS). Complete and partial remission rates were 31% and 18%, respectively, in patients with AML, and 24% and 27% in patients with MDS. Toxicity was primarily hematologic. Although in vitro data suggested that LDARA-C acts as a differentiating agent, clinical data generally indicate a cytotoxic mechanism. Given the lack of effective therapeutic options in MDS and high risk AML (patients greater than 65 years old, secondary AML), these data are encouraging. LDARA-C warrants further study, comparing continuous infusion with intermittent subcutaneous administration and comparing LDARA-C to conventional dose therapy. 1 AUTHOR van Leeuwen FE TITLE Risk of acute myelogenous leukaemia and myelodysplasia following cancer treatment. SOURCE Baillieres Clin Haematol; VOL 9, ISS 1, 1996, P57-85 (REF: 115) ABSTRACT Now that a substantial group of cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL, testicular cancer, ovarian cancer, breast cancer and paediatric malignancies. In patients with HD, the risk of AML is higher with an increasing number of mechlorethamine-procarbazine-containing cycles, a greater number of CT episodes, and after splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL, testicular cancer and breast cancer experience much lower risk of AML than patients with HD. NHL and breast cancer treatment regimens with cumulative cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased AML risk has been observed following autologous bone marrow transplantation and other dose intensification strategies. Risk factors for this excess remain to be defined. PVB treatment for testicular cancer is not followed by increased leukaemia risk, but modern etoposide-containing regimens do confer excess risk, of which the magnitude at conventional drug doses is not yet well known. High risk of leukaemia has been reported in children treated with epipodophyllotoxins. The leukaemogenic hazards of cancer treatment should be weighed against their therapeutic benefits. 10 AUTHOR Pedersen-Bjergaard J TITLE Radiotherapy- and chemotherapy-induced myelodysplasia and acute myeloid leukemia. A review. SOURCE Leuk Res; VOL 16, ISS 1, 1992, P61-5 (REF: 28) ABSTRACT A highly increased risk of myelodysplasia (MDS) and acute myeloid leukemia (AML) has been demonstrated following therapy with alkylating agents. The risk increases with cumulative dose and with the age of the patient. Most cases of MDS and AML following therapy with alkylating agents present chromosome aberrations, primarily loss of whole chromosomes No. 5 and/or No. 7 or various parts of the long arms of these chromosomes. The risk of MDS and AML following high-voltage radiotherapy is much lower. Recently an increased risk of AML has been demonstrated following therapy with the epipodophyllotoxins etoposide and teniposide. These leukemias typically present without preceding MDS and often show balanced aberrations of chromosome bands 11q23 and 21q22. 12 AUTHOR Heyman MR TITLE Recent advances in biology and treatment of myelodysplasia. SOURCE Curr Opin Oncol; VOL 3, ISS 1, 1991, P44-53 (REF: 59) ABSTRACT The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.