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Austrian researchers have reported that a small number of patients taking Janus kinase (JAK) inhibitors to treat myelofibrosis may develop aggressive lymphomas and suggest that screening for preexisting B-cell clones before starting therapy may help prevent this side effect and potentially save lives.

Myelofibrosis is a myeloproliferative neoplasms (MPN) which is part of 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’s are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Myeloproliferative neoplasms are most common in older adults. Out of every 100,000 people in the United States, an estimated 44 to 57 people have PV, and a similar number have ET. Myelofibrosis is less common, affecting 4 to 6 people per 100,000.3

In recent years improved treatment options have become more available and often target the JAK2 gene, which controls the production of blood cells. Doctors treat the condition with these medications referred to as “JAK inhibitors” which were designed to target or inhibit the action of this gene when it is faulty.

According to study coauthor Heinz Gisslinger, MD, of the Medical University of Vienna in Austria. “we started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment.”

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He assessed 626 patients receiving treatment for myeloproliferative neoplasms at the Medical University of Vienna and identified 69 that had myelofibrosis and were being treated with JAK inhibitors. Of those, four (5.8%) developed lymphomas. In comparison, they found that of the 557 patients who did not receive JAK inhibitors, only two (0.36%) developed lymphomas.

In blood samples taken from the patients with myelofibrosis the researchers found a preexisting B-cell clone in the bone marrow in three of the four patients who later developed lymphoma. Further investigation suggested that this clone was the same that later transformed into lymphoma.

The researchers believe that all patients with myelofibrosis should be tested for gene rearrangements before prescribing JAK inhibitors to treat their disease.

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