Multiple myeloma is still an incurable malignancy with low complete remission rate and a high recurrence rate by conventional therapy. The fludarabine-based regimen of eliminating the B lymphocytes may reduce or suppress the relapse of multiple myeloma. We treated the patients with relapsed and refractory multiple myeloma with FMD (fludarabine 35 mg/m2/d, d1~3, mitoxantrone 8 mg/m2/d, d1 and dexamethasone 20mg/d, d1~4). The results are encouraging. Case one: A 47 year-old female presented with lumbosacral pain (for 2 months), dull pain in the low back, palpitations, distress, and shortness of breath. Her peripheral blood examination showed that her white blood cell (WBC) count was 5.71×109/L, the hemoglobin concentration was 81 g/L and the platelet count was 181×109/L. The serum IgG was 118.0g/L, λ light chain was 115.84 g/L, globulin was 133 g/L, albumin was 26 g/L, and β2-MG was 3491.8 μg/L. The serum Ca2+ was 2.2 mmol/L. The urine Bence-Jones protein electrophoresis was negative. The immunoelectrophoretic analysis showed a monoclonal protein: IgG-lambda. A bone marrow aspirate revealed 38% plasma cells. The body bone radiograph revealed generalized osteoporosis and depressed fracture of L2 and L4. She was diagnosed as Multiple Myeloma. The patient subsequently began 5 courses of VADM every 4 weeks (vincristine 0.5 mg on Days 1–4, THP 10 mg on Days 1–4, dexamethasone 20 mg on Days 1–4, Melphan 6 mg BID on Days 1–4). The lumbodynia was relieved after chemotherapy. But after 5 courses of VADM, her hemoglobin level was 81 g/L, IgG was 40.9 g/L, λ light chain was 33.28 g/L, albumin was 56 g/L, and β2-MG was 2156.2 μg/L. A BM study showed 30% plasma cells. The body bone radiograph was the same as before. Then she was treated with 3 courses of FMD. The symptoms of lumbodynia were relieved. A bone marrow study showed 14% plasma cells. The hemoglobin level was 125 g/L, IgG was 21.9 g/L, λ light chain was 31.3 g/L, albumin was 63 g/L, and β2-MG was 1670.6 μg/L. No more new lytic lesion appeared. There were no obvious side effects during the treatment. Case two: A 57-year-old male presented with shortness of breath, palpitations caused by hard work and pain of the lower back, which had been continuing for 4 months. Prior to his admission, the bone marrow showed a 19.5% plasma cells. The immunoelectrophoretic analysis disclosed the presence of a monoclonal component of IgA-kappa protein. Serum levels of immunoglobulin were 7.45 g/L for IgA and 15.04 g/L for kappa. Serum creatinine was 123 mmol/L, BUN 5.2 mmol/L, calcium 2.3 mmol/L, β2-microglobulin 6114.5 mg/L and hemoglobin was 61 g/L. The bone X-ray showed generalized osteoporosis and depressed fracture of L2 and L4. The patient was diagnosed as multiple myeloma and received 2 cycles of M2 and 2 cycles of VAD. But his symptoms did not improve and pain increased. After admission, the BM smear showed plasma cells of 46%. Serum IgA was 9.91 g/L, kappa was 17.79 g/L, calcium was 2.5 mmol/L, β2-microglobulin was 3338.8 mg/L, and hemoglobin was 84 g/L. The patient was given treatment with the regimen of FMD, repeated every 4 weeks. Four months later, after the 3 cycles of FMD were administered, the BM showed only 16% of plasma cells in smear specimen. Serum IgA was 8.25 g/L, kappa was 8.39 g/L, creatinine was 103 mmol/L, BUN was 7.0 mmol/L, calcium was 2.2 mmol/L, β2-microglobulin was 2926.0 mg/L, and hemoglobin was 112 g/L. The bone X-ray did not show new lytic lesions. So far 8 months after finishing 8 cycles of FMD, the patient was in a good condition and had no bone pain.