Allogeneic Stem Cell Transplant vs. Janus Kinase Inhibition in the Treatment of Primary Myelofibrosis or Myelofibrosis After Essential Thrombocythemia or Polycythemia Vera
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Abstract
Primary myelofibrosis is one of the Philadelphia chromosome-negative myeloproliferative
neoplasms and is the member of that group with the worst survival and the most significant
limitations in quality of life. Hepatosplenomegaly due to extramedullary hematopoiesis,
constitutional symptoms, and cytopenias are the main manifestations. The natural history
is highly variable, and up to 30% of patients can experience acceleration to acute
myelogenous leukemia. Conventional therapy is only palliative and not always effective.
However, huge advances have been achieved in the past 2 decades toward a better understanding
of the pathogenesis of this disease, as well as improved management. Powerful risk
stratification systems are now available and can reliably separate the patients into
different prognostic categories to aid clinical management. Allogeneic stem cell transplant
can offer cure but is still not universally applicable owing to the treatment-related
mortality and toxicity. Nevertheless, outcomes of transplant are improving, owing
to the introduction of reduced-intensity conditioning regimens and the optimization
of remission monitoring techniques and relapse prevention strategies. The discovery
of the V617F mutation of JAK2 (Janus kinase 2) and some other molecular aberrations
has shed more light on the molecular pathogenesis of the disease and has led to the
introduction of novel therapies such as JAK2 inhibitors. In fact, JAK inhibitors have
shown promising symptomatic efficacy, and the JAK inhibitor ruxolitinib has also shown
a potential survival benefit. Future effort should be made to combine allogeneic stem
cell transplant with JAK inhibition.