Second cancers in MPN: Survival analysis from an international study

Marchetti, Monia; Ghirardi, Arianna; Masciulli, Arianna; Carobbio, Alessandra; Palandri, Francesca; Vianelli, Nicola; Rossi, Elena; Betti, Silvia; Veroli, Ambra Di; Iurlo, Alessandra; Cattaneo, Daniele; Finazzi, Guido; Bonifacio, Massimiliano; Scaffidi, Luigi; Patriarca, Andrea; Rumi, Elisa; Casetti, Ilaria Carola; Stephenson, Clemency; Guglielmelli, Paola; Elli, Elena Maria; Palová, Miroslava; Rapezzi, Davide; Erez, Daniel; Gómez, Montse; Wille, Kai; Pérez‐Encinas, Manuel; Lunghi, Francesca; Angona, Anna; Fox, María Laura; Beggiato, Eloise; Benevolo, Giulia; Carli, Giuseppe; Cacciola, Rossella; McMullin, Mary Frances; Tieghi, Alessia; Recasens, Valle; Isfort, Susanne; Pane, Fabrizio; Stefano, Valerio De; Grießhammer, Martin; Alvarez‐Larrán, Alberto; Vannucchi, Alessandro M.; Rambaldi, Alessandro; Barbui, Tiziano

doi:10.1002/ajh.25700

Cited by 35 publications

(44 citation statements)

References 27 publications

(51 reference statements)

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“…We found good tolerability and satisfying efficacy across all age groups (Buxhofer‐Ausch et al, manuscript in preparation) supporting earlier observations 19,20 . Broad usage of hydroxyurea in patients with MPN is discussed controversially due to a possible leukemogenic effect 21,22 . A recent publication on almost 3500 patients treated with hydroxyurea and/or anagrelide reported cases of secondary leukaemia only in the patients with hydroxyurea exposure but none in the patients with sole anagrelide treatment 23 .…”

Section: Discussionsupporting

confidence: 84%

Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia

Buxhofer‐Ausch

Wolf

Sormann

et al. 2020

European J of Haematology

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Objectives Cell counts have a significant impact on the complex mechanism of thrombosis in patients with essential thrombocythemia (ET). We recently demonstrated a considerable impact of white blood cell (WBC) counts on thrombotic risk in patients with optimized platelet counts by analysing a large anagrelide registry. In contrast, the current analysis of the registry aimed to estimate the influence of platelet counts on thrombotic risk in patients with optimized WBC counts. Methods Cox regression analysis and Kaplan‐Meier plot were applied on all patients in the registry with optimized WBC counts. Results By using the calculated cut‐off of 593 G/L for platelets, Cox regression analysis revealed a clear influence of elevated platelet counts on the occurrence of a major thrombotic event (P < .001). A Kaplan‐Meier plot revealed a markedly shorter time to a major thrombotic event for patients with platelet counts above the cut‐off (P < .001). Conclusions The data show clear impact of platelet lowering on the thrombotic risk in ET patients with normal WBC counts. Therefore, selective platelet lowering with anagrelide appears sufficient for thrombotic risk reduction in WHO‐diagnosed ET patients lacking leukocytosis.

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Section: Discussionsupporting

confidence: 84%

Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia

Buxhofer‐Ausch

Wolf

Sormann

et al. 2020

European J of Haematology

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“…Intriguingly, a recent study suggests that active MPN treatment may negatively affect survival in second cancer. However, the mechanism, e.g., suboptimal second cancer management, is unknown [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Risks of Solid and Lymphoid Malignancies in Patients with Myeloproliferative Neoplasms: Clinical Implications

Brabrand

Frederiksen

2020

Cancers

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In the past decade, several studies have reported that patients with chronic myeloproliferative neoplasms (MPNs) have an increased risk of second solid cancer or lymphoid hematological cancer. In this qualitative review study, we present results from studies that report on these cancer risks in comparison to cancer incidences in the general population or a control group. Our literature search identified 12 such studies published in the period 2009–2018 including analysis of more than 65,000 patients. The results showed that risk of solid cancer is 1.5- to 3.0-fold elevated and the risk of lymphoid hematological cancer is 2.5- to 3.5-fold elevated in patients with MPNs compared to the general population. These elevated risks apply to all MPN subtypes. For solid cancers, particularly risks of skin cancer, lung cancer, thyroid cancer, and kidney cancer are elevated. The largest difference in cancer risk between patients with MPN and the general population is seen in patients below 80 years. Cancer prognosis is negatively affected due to cardiovascular events, thrombosis, and infections by a concurrent MPN diagnosis mainly among patients with localized cancer. Our review emphasizes that clinicians caring for patients with MPNs should be aware of the very well-documented increased risk of second non-myeloid cancers.

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“…Leukemic transformation was associated with treatment with pipobroman, P 32 or chlorambucil but not with hydroxyurea or busulfan 32. Whether or not the same holds true for second cancers developing in patients with MPN remains to be clarified 106. Recommendations in the management of high risk patients with PV or ETIn addition to low-dose aspirin and phlebotomy to a hematocrit target of 45%, in case of PV, high-risk patients with PV or ET should receive hydroxyurea, as first-line cytoreductive drug of choice, in order to minimize their risk of thrombosis (starting dose 500 mg BID)(Figures 3 and 4).…”

mentioning

confidence: 97%

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

2020

Self Cite

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) respectively characterized by clonal erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR or MPL mutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are approximately 15 years for PV and 18 years for ET; the corresponding values for patients age 40 or younger were 37 and 35 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET but risk of thrombosis is higher in JAK2 mutated cases. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis risk: In PV, two risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wildtype), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild-type) and high (thrombosis history present or age > 60 years with JAK2 mutation). Risk-adapted therapy: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications. Very low risk ET might not require therapy while aspirin therapy is advised for low risk disease. Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs

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Second cancers in MPN: Survival analysis from an international study

Cited by 35 publications

References 27 publications

Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia

Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia

Risks of Solid and Lymphoid Malignancies in Patients with Myeloproliferative Neoplasms: Clinical Implications

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

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