Arsenic Trioxide (Trisenox®) with/without Thalidomide in Patients with Myelodysplastic Syndromes (MDS) Produces Hematologic Improvement (HI).

In a previous clinical trial, we have shown that 7/28 MDS patients, belonging to IPSS intermediate and high risk categories, responded to a combination of Trisenox® and thalidomide including a complete hematologic and cytogenetic remission. Two trilineage responses were seen in patients with inv(3) abnormality. It was not clear whether the responses were due to the combination or to either drug alone. In the present study, we treated 30 MDS patients with Trisenox® (5 days of loading dose at 0.25mg/kg IV over 2 hours followed by twice weekly dose) for 6 months followed by the addition of thalidomide (100mg po qday x 3 months). The Median age was 71 years (19 males, 11 females). FAB types: RA 3 patients, RARS 2, RAEB 14, RAEB-t 8, CMMoL 2, Unclassified 1. IPSS: Low 0 patients, Int-1 10, Int-2 7, High 13. Two, 1,1 and 4 patients had abnormalities affecting chromosomes 5, 7, 8, and 20, while 12 patients showed a complex karyotype. Therapy was fairly well tolerated and median number of cycles was 3. Five patients showed a variety of hematologic responses as judged by the IWG criteria (1 trilineage, 1 cytogenetic and change in FAB type due to decrease in blasts, 1 ANC and reduction in blasts, and 2 with 50% reduction in blasts). Among the responders, 1 had 47 XX, +8(16 metaphases), del(X)(q22q25),del(3)(q25q27)(4 metaphases), 3 had a normal karyotype, and 1 had del(20q). Three of the partial responders were started on thalidomide, but all stopped within 2 months. Following response, the first patient showed disappearance of the clone bearing the chromosome 3 abnormality, confirming the sensitivity of these cells to Trisenox® as reported in our previous trial. Interestingly, 3/5 responders showed an increase in WBC/ANC and 1 in platelets as well (12, 22 and 90,000/ul), without any evidence of a differentiation syndrome. One also had an increase in platelets from ~50,000/ul to 966,000/ul. Blasts were 11, 24 and 28% in these 3 patients prior to therapy and decreased to 4, 6 and 24% respectively after treatment. It was concluded that the twice-daily dose of arsenic trioxide was well tolerated, and some patients converted their disease to a more myeloproliferative type picture.