Improvement in cytopenias of patients with myelodysplastic syndromes (Mds) In response to thalidomide

Abstract Recent studies investigating the pathogenesis of MDS have yielded two important biological insights, both of which can be exploited for therapeutic purposes. The first is that cytopenias may be the result of excessive cytokine-induced apoptosis of hematopoietic cells, and second that the bone marrows (BM) of MDS patients are highly vascular. Thalidomide was chosen as a potentially useful agent since it has both anti-cytokine and anti-angiogenic properties. The protocol provided for a starting dose of 100 mg po qhs of thalidomide, increased as tolerated to 400 mg. Patients belonging to all FAB categories were eligible. Response meant an increase in Hb by 2.0 Gm/dL and/or a 50% reduction in packed red blood cell (PRBC) transfusions, increase in platelets by 30,000/μl or increase in absolute neutrophil count (ANC) by 500/μl. 83 patients with a confirmed diagnosis of MDS have been accrued on the study and 31 have completed 12 weeks and are available for response evaluation. The median age was 68 years; there were 19 males and 12 females. 18 had RA, 6 RARS, 6 had RAEB, and 1 had CMMoL. 29 had primary MDS, while 2 had received prior therapy for breast cancer. Twenty-four patients were dependent on PRBC transfusions, while 6 were platelet dependent. The most frequent side effects were constipation, fatigue, and fluid retention while neuro-toxicity was avoided to a large extent because of prophylaxis with pyridoxine. 21 patients experienced rather significant partial response. The most striking responses were seen in the erythroid series with 8 patients achieving complete transfusion independence and 13 increasing their hemoglobin by more than 2 Gm/dL. Among the 13 platelet responders, there were 3 who increased their counts by >2000,000/μl and 4 by 100,000/μl. The best responses were seen in the RA/RARS patients, while 3/6 RAEB patients showed some disease evolution. Interestingly, 2 patients showed a response only after thalidomide was stopped. One of these in fact improved his hemoglobin from 7 to 16 Gm/dL, his platelets from 18,000/μl to 71,000/μl and normalized his ANC a full THREE months after stopping thalidomide, mimicking the effect of ATG and suggesting an immune-modulatory role of thalidomide in addition to its ant-cytokine and anti-angiogenic actions. In summary therefore, thalidomide is an exciting new addition to MDS therapeutic armament and needs further investigations.