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Authors Call for More Research on Rare Blood Cancers to Fill Knowledge Gaps


Authors hope that identifying knowledge gaps surrounding rare blood cancers, such as essential thrombocythemia and polycythemia vera, will inspire the science community to invest in new comprehensive research on how to properly diagnose and treat patients.

Despite advancements in diagnostic, prognostic, and therapeutic processes there remain uncertainties regarding aspects of decision making that indicate new research on rare blood cancers, such as essential thrombocythemia (ET) and polycythemia vera (PV), need to be conducted, according to a paper published in Haematologica.

“Well organized observational and registry-based studies will play a key role in analyzing the clinical outcomes, hopefully with the help of a data mining approach and artificial intelligence techniques, as suggested by preliminary experiences in patients with PV treated with ruxolitinib,” wrote the authors.

ET and PV are subtypes of cancers a part of a larger group of related blood cancers called myeloproliferative neoplasms. ET is caused by an overproduction of blood platelets, leading to increased risk of thrombosis and other serious conditions. PV is caused by an overproduction of red blood cells, causing blood to be thick and flow slowly.

Regarding diagnostic criteria, the World Health Organization in 2016 introduced the concept that some patients with ET may actually have pre-fibrotic primary myelofibrosis (pre-PMF). Reference institutions speculate that about 15% to 30% of patients with ET could be reclassified as pre-PMF.

Studies have shown that the risk of blood clot development is similar between the 2; however, incidence of bleeding episodes is more frequent for patients with pre-PMF compared with patients with “true” ET. Survival rates were also different, ranging from 10.5 years to 14.7 years for patients with pre-PMF compared with 14.7 years to 21.8 years for patients with ET.

“Since expected survival is the key issue to discuss with a patient newly diagnosed with pre-PMF, acquiring such information definitely represents the most compelling unmet need in [patients with] pre-PMF,” wrote the authors.

Research for diagnostic and prognostic criteria may be most helpful and timely coming from conducting a study enrolling both incident and retrospective cases or by creating and making available a comprehensive clinical and biologic database.

The authors wrote that these approaches could help identify causes of death in patients with pre-PMF, rate of transformation to overt PMF and acute leukemia, and allow predictive variables to be identified.

Risk of thrombosis may change for patients with ET and PV as a result of gene mutations. In patients with ET, CALR gene mutations have been shown to correlate with lower thrombosis risks compared with patients with JAK2 V617F mutations. JAK2 V61F allele burdens may increase thrombosis risks in patients with PV as well; however, more data is needed to confirm whether genetic evaluation provides clinically relevant information.

Additionally, assessing the risk of thrombosis can be difficult as the distinction of patients at low risk is weakening. Patients treated with phlebotomy and low-dose aspirin (LDA) still exhibit a 2% annual rate of major thrombotic episodes, calling into question whether these treatment methods are appropriate.

The quality of data surrounding the use of LDA is also low despite being stemmed from a phase 3 trial in patients with PV and retrospective studies in patients with ET. New hypotheses are currently being tested to improve aspirin efficacy in thrombosis prevention.

Cytoreductive drugs may offer greater benefit than phlebotomies, however experts discouraged the use of cytoreductive drugs in young patients as there may be leukemogenic risks associated with currently available products, such as hydroyurea, which has shown efficacy in preventing arterial thromboses but may not prevent recurrent venous thromboembolism.

“We believe that young patients with no history of previous thrombosis could be exposed to cytoreductive treatment as long as they only receive drugs for which there is no evidence of promoting secondary leukemias or solid tumors,” explained the authors in response to seeing promising results from trials testing the effects of new cytoreductive drugs, interferon and Ropeginterferon ⍺-2ba.

The risk of transformation into acute myeloid leukemia (AML) for patients with PV or ET is estimated at 3% and 1%, respectively, after 10 years. Currently, there is no evidence that drugs such as hydroxyurea, interferon, anagrelide, or ruxolitinib can slow down transformation risks.

There is hope that new targeted drugs such as idasanutlin in patients with PV and givinostat in patients with PV or ET could reduce AML transformation risks. The effects other promising drugs including enasidenib and ivosidenib in combination with other forms of treatment, venetoclax, navitoclax, and CPX-351, are currently under investigation.

“At the moment, results from rigorously designed clinical trials in this category of high-risk patients are still lacking and the little interest…to promote studies in this setting represents a major problem. It is, therefore, a clear duty of the scientific community to promote academic trials for this unmet clinical need,” the authors wrote.


Barbui T, Vannucci AM, Guglielmelli P, Stefano V, Rambladi A. An agenda for future research projects in polycythemia vera and essential thrombocythemia. Haematol. 2020; 105(8):1-4. doi:10.3324/haematol.2019.246207

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