by Dr.C.H. Weaver M.D. updated 09/2021
Myeloproliferative neoplasms (MPN) are a related group of blood cancers. In these disorders, the bone marrow cells that produce blood cells develop and function abnormally. The three main types of MPN are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In addition to developing on its own, myelofibrosis may also develop as a result of ET or PMF. Treatment options have become more available in recent years and treatment has been shown to provide improvement of symptoms and prolong survival.1,2 In rare cases however, MPN’s can transform into a fast-growing type of blood cancer known as acute myeloid leukemia.
Treatment options are limited for patients with advanced MPNs including “blast-phase disease” and progression to leukemia. Dacogen (decitabine) has frequently been deployed for treatment of these patients due to its effectiveness in treating other blood cancers but its effectiveness and safety profile are not well described in patients with MPNs.
Dacogen is a DNA "demethylating" agents. Methylation of DNA is a major mechanism that regulates gene expression in cells. When there is an increase in DNA methylation this can result in the blockage of the activity of "suppressor genes" that regulate cell division and growth. When suppressor genes are blocked, cell division becomes unregulated, allowing or promoting cancer.
Dacogen's anticancer effects are believed to be twofold. One way that it works is by demethylation or interfering with the methylation of DNA. By this process of demethylation, normal function to the tumor suppressor genes is restored, thus restoring control over cell growth. More about Dacogen
Researchers retrospectively evaluated 42 patients (16 with MPN-BP, 14 with MPN accelerated-phase [MPN-AP], and 12 with myelofibrosis with high-risk features treated with Dacogen alone or in combination with Jakafi (ruxolitinib). Compared with Dacogen monotherapy, Dacogen plus Jakafi appeared to improve average survival duration from 13 to 21 months.3
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Dacogne alone or in combination with Jakafi appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course according to the study authors. While stem cell transplant is the best treatment option for MPN patients with advanced disease, Dacogen and Jakafi appear to be effective for controlling therapy in transplant ineligible patients and for those that need effective disease control who are awaiting transplant.
- Annucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-191.
- Hultcrantz M, Kristinsson SY, Andersson TM, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:2995-3001.
- Acta Haematol. 2021;144:48-57