Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia

We present five cases of concomitant relapsed multiple myeloma and therapy related myelodysplasia (t-MDS). After treatment with thalidomide marked anti-myeloma activity was observed, but it was associated with rapid progression of the MDS clone to acute myeloid leukemia (AML). This paradoxical effect of thalidomide is concerning because there is increasing use of thalidomide in relapsed, heavily treated multiple myeloma patients who already have a higher propensity to develop MDS. The leukemic transformation in our cases most probably reflects the natural progression of MDS, though it clearly demonstrates that thalidomide is ineffective in controlling blast proliferation in t-MDS. More concerning, however, is the possibility that thalidomide, while suppressing the myeloma clone, eliminates inhibitory signals and subsequently stimulates the proliferation of the leukemic clone. The use of thalidomide should be carefully assessed in relapsed multiple myeloma patients with clinical and cytogenetic evidence of t-MDS.