Therapy associated myelodysplastic syndromes (tMDS) and acute myelogenous leukemia (tAML) have been seen with increasing frequency following high dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT). However, tMDS and tAML can also develop following the use of standard doses of chemotherapy and radiation for the treatment of patients for malignancy. Some investigators have hypothesized that the preparative regimen for transplant is the primary etiology for the post AHSCT tMDS/tAML. Other investigators have hypothesized that it is the exposure to the prior chemotherapy and/or radiation therapy that causes the cytogenetic abnormalities in the hematopoietic stem cells. These stem cells are then collected and stored and are given back to patients following the high dose therapy. While the tMDS/tAML is then expressed post AHSCT, the etiology is the prior treatment. Standard cytogenetic analysis of bone marrow samples prior to transplant has not proven to be sensitive enough to reliably detect which patients are at the highest risk for developing tMDS/tAML. However, in a pilot study using FISH, 9 of 12 patients who developed tMDS/tAML following AHSCT were found to have the same cytogenetic abnormality in the pre-transplant samples strongly suggesting that the latter hypothesis is correct. In none of the patients tested did standard cytogenetic analysis of metaphase karyotypes detect the cytogenetic abnormality. This proposal will expand the experience of using FISH to detect tMDS/tAML associated cytogenetic abnormalities to determine the sensitivity of this technique. If FISH can be shown to reliably predict which patients are at high risk for the development tMDS/tAML, these patients should be excluded from AHSCT and alternative treatment approaches could be applied.

R21CA085416

2001-03-01

2004-02-29