New discovery can make an existing leukemia treatment more effective
Prolymphocytic leukemia (PLL) is a rare and aggressive form of malignancy characterized by marked lymphocytosis and splenomegaly. PLL represents only 2% of all chronic lymphoid leukemias in adults over the age of 30. Most patients with PLL shows involvement of the peripheral blood, bone marrow, lymph nodes, liver, and spleen. In addition, skin infiltration and serious effusions may also occur at rates of approximately 25 and 15 percent, respectively.
Despite advances in the understanding of the biology and pathogenesis of this disease, the prognosis for these patients remains very poor, with short survival and no curative therapy. Currently, intravenous alemtuzumab is one of the best available treatments for PLL, which has improved the rate of remission to more than 50% and the duration of response to between 6 and 12 months. Autologous or allogeneic stem cell transplantation may further prolongs survival. However, despite continuous progress, existing treatments are not curative. Most patients with PLL will still die because of the disease's resistance to conventional chemotherapy. Therefore, new therapies that can successfully solve the resistance related puzzle are sorely needed.
Recently, Hasanali and colleagues have made a breakthrough in leukemia therapeutics by showing that epigenetic therapy may overcome alemtuzumab resistance and increase the patient survival rate . At present, several epigenetic therapies are already approved by the FDA, and many of them are still in clinical trials. The group conducted a small pilot study with a case series of eight T cell prolymphocytic leukemia (T-PLL) patients who were treated with cladribine, vorinostat/romidepsin/valproic acid, and alemtuzumab. They conducted a combinational therapy of demethylating agents, histone deacetylase (HDAC) inhibitors, and the immunotherapeutic agent brentuximab vedotin, to treat eight patients suffering from T-PLL resistant to the conventional alemtuzumab treatment. Remarkably, seven out of the eight patients that received this treatment achieved complete remission, and the eighth patient achieved partial remission.
However, there are still some limitations to the experimental approach, such as systemic toxicity, and immunosuppression can lead to infections and other complications. But the treatment made a significant difference and might hold great promise for combatting drug resistance for other types of cancers as well.
1. Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia, Science Translational Medicine 24 Jun 2015: Vol. 7, Issue 293, pp. 293ra102