Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger

Szuber, Natasha; Vallapureddy, Rangit; Penna, Domenico; Lasho, Terra L.; Finke, Christy; Hanson, Curtis A.; Ketterling, Rhett P.; Pardanani, Animesh; Gangat, Naseema; Tefferi, Ayalew

doi:10.1002/ajh.25270

Cited by 69 publications

(114 citation statements)

References 33 publications

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“…14,15 In MPN, the rate of leukemic transformation was similar in patients across all age groups. 7,11,13,16 In line with these previous studies, the 10-year risk of patients with PV to develop fibrosis was 13%, within the 2.3% and 23% range that was reported for patients at all ages. 16,17 In ET, on the other hand, the 10-year risk of fibrotic transformation was 20%, similar to what was recently reported in young adults 7 but 5 times higher than what was reported in another cohort of young patients.…”

Section: Discussionsupporting

confidence: 87%

Characteristics and outcomes of young adults with Philadelphia‐negative myeloproliferative neoplasms

Barzilai

Kirgner

Avivi

et al. 2019

European J of Haematology

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Objective Approximately 10% of Philadelphia (Ph)‐negative myeloproliferative neoplasms (NPM) are diagnosed at young adulthood. We aim to define the features of this group. Methods A multicenter retrospective study, including patients 18‐45 years of age, diagnosed with Ph‐negative MPN between 1985 and 2017. Results One hundred nine patients were included, 37 with polycythemia vera (34%), 54 with essential thrombocytosis (50%), 15 with primary myelofibrosis (PMF) (14%), and 3 with MPN unclassifiable (3%). Median age was 33 years and 62 (57%) were females. During a median follow‐up of 8 years, 39 patients (37%) had at least one thrombotic event. 30/39 of events were venous (77%), 23/30 of which were splanchnic (77%). In 14/39 (36%), thrombosis preceded MPN diagnosis. In a multivariable analysis, only splenomegaly predicted for thrombosis (HR 5.6, CI: 1.4‐22). The 10‐year risk for secondary myelofibrosis was similar for ET and PV (0.13 vs 0.19, P = 0.51). The 10‐year risk for leukemic transformation or mortality was significantly higher for PMF (0.3, P = 0.04). Conclusions The risks of mortality and of progression to MF/leukemia in young adults are similar to older population. Thrombotic events are frequently a presenting sign with a high incidence of venous, in particular splanchnic, events.

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Section: Discussionsupporting

confidence: 87%

Characteristics and outcomes of young adults with Philadelphia‐negative myeloproliferative neoplasms

Barzilai

Kirgner

Avivi

et al. 2019

European J of Haematology

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“…86 Therefore, it is very important to avoid nonevidence-based therapeutic adventures in PV or ET that might shorten life-expectancy and increase the rate of fibrotic or leukemic transformations, as has been previously documented for chlorambucil, 53 radiophosphorus, 54 pipobroman, 87 and most recently for anagrelide. 86 Therefore, it is very important to avoid nonevidence-based therapeutic adventures in PV or ET that might shorten life-expectancy and increase the rate of fibrotic or leukemic transformations, as has been previously documented for chlorambucil, 53 radiophosphorus, 54 pipobroman, 87 and most recently for anagrelide.…”

Section: Discussionmentioning

confidence: 99%

“…Median survival in young patients with PV and ET might exceed 30 years and is not that much worse for older patients. 86 Therefore, it is very important to avoid nonevidence-based therapeutic adventures in PV or ET that might shorten life-expectancy and increase the rate of fibrotic or leukemic transformations, as has been previously documented for chlorambucil, 53 radiophosphorus, 54 pipobroman, 87 and most recently for anagrelide. 64 To date, drug therapy has not been shown to improve survival or prevent leukemic/fibrotic transformation in either ET or PV and treatment is primarily directed at preventing thrombotic complications.…”

Section: Discussionmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

2018

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Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by 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 myeloproliferative leukemia mutations. In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are 14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 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. Risk of thrombosis is higher in JAK2‐mutated ET. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors); in ET, 4 risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild‐type), 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‐ 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 of choice are interferon‐α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.

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“…[1][2][3][4] To date, drug therapy has not been shown to improve survival in ET and treatment is primarily indicated in order to prevent thrombotic complications. [1][2][3][4] To date, drug therapy has not been shown to improve survival in ET and treatment is primarily indicated in order to prevent thrombotic complications.…”

Section: Introductionmentioning

confidence: 99%

“…Life-expectancy in essential thrombocythemia (ET) is shorter than expected from the age-and sex-matched control population but is significantly better than that of other myeloproliferative neoplasms (MPN), including polycythemia vera (PV) and myelofibrosis (MF), with median survival for patients younger than 60 years of age approaching 33 years. [1][2][3][4] To date, drug therapy has not been shown to improve survival in ET and treatment is primarily indicated in order to prevent thrombotic complications. Accordingly, lower risk patients are managed by aspirin therapy or observation alone while cytoreductive therapy is reserved for high risk disease.…”

Section: Introductionmentioning

confidence: 99%

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

et al. 2018

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First‐line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second‐line drugs of choice include pegylated interferon‐α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928‐1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis‐free (MFFS) and thrombosis‐free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1‐1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7‐6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.

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Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger

Cited by 69 publications

References 33 publications

Characteristics and outcomes of young adults with Philadelphia‐negative myeloproliferative neoplasms

Characteristics and outcomes of young adults with Philadelphia‐negative myeloproliferative neoplasms

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

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