Thalidomide is a highly effective treatment of MDS: a single-hospital experience in Japan

Abstract

Myelodysplastic syndromes (MDS) are heterogeneous stem cell diseases for which there is thought to be no curative therapy apart from stem cell transplantation. However, several novel approaches, such as the use of thalidomide, have been proposed for the treatment of MDS [1–6]. Our pilot study into the use of thalidomide as a treatment, as approved by the ethical committee of our hospital, began in March 2008 and continued through to October 2008. The subjects were seven consecutive male patients (patients 1– 7, median age 69 years, range 39–89) (Table 1). The median interval of MDS before entry into the study was 10 months (range 0–42). Most prior treatments were with prednisolone or cyclosporine-A. However, patient 5 was being treated by cytotoxic chemotherapy of cytosine arabinoside and aclarubicin when he developed leukemia cutis (blast cells were 13% of those in bone marrow). He obtained complete remission before starting on thalidomide. Patient 5, as well as two others (patients 2 and 3), was also transfusion dependent because of either anemia or thrombocytopenia at the time of enrollment. Thalidomide administered at 100 mg/day resulted in the discontinuation of transfusions in all three patients. The duration of the hematological response was 80 days in patient 5, 133 days in patient 3, and 262 days in patient 2. The responses were assessed using the IWG criteria [9]. Five patients, including these three, had erythroid responses; three of the five showed improvements in their platelet count. Patient 4, though alive, could not be assessed because of frequent nasal bleeding. Patient 7 showed some response, but none met the criteria, and death from a non-hematological disease occurred about 6 months after treatment. Two patients, 3 and 5, died after developing overt leukemia. Patient 5 showed good hematological improvement, but in a span of just 80 days developed leukemia. He was administered alloBMT, but died of GVHD. Patients 1, 2, and 6 were alive at the time of writing, and showed hematological improvement without the need for transfusion. All three continued taking thalidomide, with the median duration of their response being 262 days. No patients discontinued the drug because of any side effects. The rates of hematological improvement were different, and the time taken to reach the peak also differed. Responses could be divided into early and late ones. Early response was defined as when the peak of Hb or platelets occurred2100 days, while a late response was defined as when the peak was documented as occurring [100 days from the start of thalidomide treatment. The median days for the early Hb response group was 67 days (range 17–72) and for the late Hb response group it was 148 days (range 124–156). The median days for the early platelet response group was 41 days (range 10–82) and for the late platelet response group it was 220 days (range 140– 300). The time delay for the late responses could have occurred through the action of thalidomide on the stem cells or by their maturating process. Cytogenetic analysis showed that four patients had normal karyotypes and that the other three had abnormal ones. Chromosome studies of bone marrow were performed on all patients at diagnosis and followed. Patient 4 had trisomy 8, and there has been no clonal evolution since diagnosis. This patient had an early response in his erythrocytes, but has not been able to be assessed since, as noted above. Patient 3 showed deletion of an abnormal karyotype during the period of hematologic K. Hayashi (&) Department of Hematology, Hirakata Kohsai Hospital, 1-2-1 Fujisakahigashimachi, Hirakata, Osaka 573-0153, Japan e-mail: kunio-h@po.sphere.ne.jp