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Median follow up was 4.2 months (range, 1.7�C21.4) from cyclophosphamide administration. Response was assessed four to six weeks after administration of cyclophosphamide. Overall, nine patients had a partial response or better (52.9%, 95%C.I. 29.2�C76.7%), including 4 patients with a very good partial response (23.5%, 95%C.I. 3.4�C43.7%). All the remaining patients had stable disease. Five of the 12 patients previously treated with at least one IMiD obtained a response (41.6%) along with 4/7 patients previously treated with an alkylating agent (57.1%). Median overall survival was 14.1 (��7.1) months (see Fig. 1). Interestingly, all six patients with plasma cell leukemia had complete clearance of plasma cells from the peripheral blood. Among the 12 patients with intent to proceed with HSCT http://www.selleck.cn/products/Staurosporine.html (cyclophosphamide used as ��bridge�� therapy), eight patients underwent either autologous (n = 7) or allogeneic (n = 1) transplantation. The median survival for these patients is estimated at 21 months. The remaining four patients did not receive HSCT because of refusal (n = 1), fast disease progression (n = 2), or worsening performance status and comorbidities (n = 1). Overall, eight patients have died, one due to toxicity of treatment and seven from disease progression. Alkylating agents are an important component of both conventional and high-dose chemotherapy-based treatment of MM. In recent years, due to the enthusiasm about new biological agents and the concerns http://www.selleckchem.com/products/epz-5676.html regarding impairment of future HSC mobilization, alkylating agents have often been avoided in the initial management of MM. We believe that many of the patients becoming refractory to proteasome inhibitors http://www.selleckchem.com/products/ly2109761.html and IMiDs were still sensitive to alkylating agents and could be rescued with high-dose cyclophosphamide without HSC support. There are few series on the management of MM refractory to proteasome inhibitors and IMiD [21]. These patients should be urged to participate in clinical trials with new drugs, including new proteasome inhibitors, histone deacetylase inhibitors, anti-CS1 antibodies and third generation IMiDs. A recent report including 270 ��double refractory�� patients from the Multicenter International Myeloma Working Group indicates a median survival of eight months from the time the patients failed last therapy. Remarkably, only 30% of patients had an objective response to the subsequent line of therapy [12]. Even though the present series include higher proportions of patients with Stage 3 disease at the diagnosis, unfavorable chromosomal abnormalities, and 3 or more prior lines of therapy, objective response (partial response or better) was documented in 52.9% of the patients. Another interesting observation is that all six patients with plasma cell leukemia had clearance of circulating plasma cells within four weeks of administration of cyclophosphamide. Comparisons between our series and the much larger series by Kumar et al.