Factors Involved in Response to Thalidomide in Myelodysplastic Syndrome: Impace of HLA and Prognostic Factors

Myelodysplastic Syndrome (MDS) is a clonal disease of hematopoiesis characterized by dysplasia in one or more lineages. Since the syndrome is clinically heterogenous, treatment options are complex and hard to define. Thalidomide (T) is the first agent tested in MDS for its immunomodulatory and anti-angiogenic effects. Twenty to 59 % response rates, which is mainly hematological improvement, have been reported. However, because of excessive toxicity and low response rates, thalidomide has not been widely used as an effective treatment option for MDS. Factors invoved in response to T are not well delineated. Better response to immunosupression (IS) in HLA-DRB1*15(+) patients with aplastic anemia and some MDS subgroups have been reported. In this study, the medical records of MDS patients, who received T at least for ≥ 3 months were retrospectively analyzed. Responses could be evaluated in 47 patients with a median age of 59 years (range, 15–84) and M/F: 29/18. According to WHO classification, there were 7 refractory anemia (RA), 9 refractory anemia with ring sideroblasts (RARS), 5 refractory cytopenia with multilineage dysplasia (RCMD), 2 RCMD-RA, 13 RCMD-RS, 6 Hypoplastic MDS, 1 RAEB, 4 MDS/MF. International Prognostic Scoring (IPSS) risk groups consisted of 42 low/intermediate-1 and 5 intermediate-2/high risk patients. Clonal cytogenetic abnormalities were found in 16 patients (5 trisomy 8, 3 monosomy 7, 2 delY, 2 increased chromosomal breaks, 1 del5q, 1 monosomy 15 and 1 del21q). Thalidomide was administered at a dose range of 100–400mg/day and for a range of 3–48 months. Twenty-one patients had hematological response (10 major and 11 minor). Seven patients among responders had received additional erythropoietin (EPO) combined with T. There was no statistically significant difference between responders and non-responders in terms of age (median 53 vs 60.5 years), sex (M/F: 12/9 vs 17/26) and IPSS risk groups (Low risk/high risk: 19/2 vs 23/3). Response rates were 44% in RA; 50% in RCMD-RA; 56% in RARS; 55% in RCMD-RS; 20% in RCMD; 20% in hypoplastic MDS; 75% in MDS/MF. and none in RAEB patient. The EPO levels did not differ significantly between the responders and non-responders (EPO miu/ml <500 in 93% vs 83%). However, compared with non-responders, majority of the responders had ferritin levels <1000 mcg/L (83% vs 50%, p<0.05). A total of 21 patients had their HLA type screened. HLADRB1*15 was detected in 44% of responders (4/9) and 16% of non-responders (2/12) (p<0.05). Interestingly, among 5 patients who had trisomy 8, 4 responded to T. Fourty-five percent of mainly low risk-MDS patients responded to T. Patients with MDS/MF and RARS/RCMD-RS and patients with less iron overload responded better. HLADRB1*15 predominance and the presence of trisomy 8 in T responders should be underlined.