The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients
Abstract We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00960-1 |
| _version_ | 1797388542378246144 |
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| author | Tiziano Barbui Alessandra Carobbio Juergen Thiele Naseema Gangat Elisa Rumi Alessandro Rambaldi Alessandro M. Vannucchi Ayalew Tefferi IWG-MRT group |
| author_facet | Tiziano Barbui Alessandra Carobbio Juergen Thiele Naseema Gangat Elisa Rumi Alessandro Rambaldi Alessandro M. Vannucchi Ayalew Tefferi IWG-MRT group |
| author_sort | Tiziano Barbui |
| collection | DOAJ |
| description | Abstract We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median follow-up of 6.9 years, 347 (23%) deaths, 50 (3%) blast phase (BP), and 138 (9%) fibrotic (post-PV MF) transformations were recorded. Incident thrombosis occurred at a rate of 2.62% pt/yr (arterial 1.59% and venous 1.05%). The probability of death, in the first 10 years, for 280 (18%) patients who developed thrombosis during follow-up was 40%, which was two-fold higher than that seen in the absence of thrombosis or any other transition state (20%; p < 0.01); the adverse impact from thrombosis was more apparent for arterial (HR 1.74; p < 0.01) vs venous thrombosis (p=NS) and was independent of other fixed (i.e., age, prior venous thrombosis, leukocytosis) or time-dependent (i.e., progression to BP or MF) risk variables. The transition probability to post-PV MF increased over time, in a linear fashion, with a rate of 5% capped at 5 and 10 years, in patients with or without incident thrombosis, respectively. The impact of thrombosis on transition probability to death or post-PV MF tapered off beyond 10 years and appeared to reverse direction of impact on MF evolution at the 12-year time point. These observations suggest thrombosis in PV to be a marker of aggressive disease biology or a disease-associated inflammatory state that is consequential to both thrombosis and disease progression. |
| first_indexed | 2024-03-08T22:41:20Z |
| format | Article |
| id | doaj.art-6474a721d23f450c80a8f7af9c2595d4 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-03-08T22:41:20Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-6474a721d23f450c80a8f7af9c2595d42023-12-17T12:07:33ZengNature Publishing GroupBlood Cancer Journal2044-53852023-12-011311510.1038/s41408-023-00960-1The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patientsTiziano Barbui0Alessandra Carobbio1Juergen Thiele2Naseema Gangat3Elisa Rumi4Alessandro Rambaldi5Alessandro M. Vannucchi6Ayalew Tefferi7IWG-MRT groupFROM Research Foundation, Papa Giovanni XXIII HospitalFROM Research Foundation, Papa Giovanni XXIII HospitalInstitute of Pathology, University of CologneHematology Division, Mayo ClinicDepartment of Molecular Medicine, University of PaviaHematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIIICenter Research and Innovation of Myeloproliferative Neoplasms (CRIMM), Department of Experimental and Clinical Medicine, Azienda Ospedaliera Universitaria Careggi, University of FlorenceHematology Division, Mayo ClinicAbstract We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median follow-up of 6.9 years, 347 (23%) deaths, 50 (3%) blast phase (BP), and 138 (9%) fibrotic (post-PV MF) transformations were recorded. Incident thrombosis occurred at a rate of 2.62% pt/yr (arterial 1.59% and venous 1.05%). The probability of death, in the first 10 years, for 280 (18%) patients who developed thrombosis during follow-up was 40%, which was two-fold higher than that seen in the absence of thrombosis or any other transition state (20%; p < 0.01); the adverse impact from thrombosis was more apparent for arterial (HR 1.74; p < 0.01) vs venous thrombosis (p=NS) and was independent of other fixed (i.e., age, prior venous thrombosis, leukocytosis) or time-dependent (i.e., progression to BP or MF) risk variables. The transition probability to post-PV MF increased over time, in a linear fashion, with a rate of 5% capped at 5 and 10 years, in patients with or without incident thrombosis, respectively. The impact of thrombosis on transition probability to death or post-PV MF tapered off beyond 10 years and appeared to reverse direction of impact on MF evolution at the 12-year time point. These observations suggest thrombosis in PV to be a marker of aggressive disease biology or a disease-associated inflammatory state that is consequential to both thrombosis and disease progression.https://doi.org/10.1038/s41408-023-00960-1 |
| spellingShingle | Tiziano Barbui Alessandra Carobbio Juergen Thiele Naseema Gangat Elisa Rumi Alessandro Rambaldi Alessandro M. Vannucchi Ayalew Tefferi IWG-MRT group The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients Blood Cancer Journal |
| title | The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients |
| title_full | The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients |
| title_fullStr | The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients |
| title_full_unstemmed | The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients |
| title_short | The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients |
| title_sort | impact of thrombosis on probabilities of death and disease progression in polycythemia vera a multistate transition analysis of 1 545 patients |
| url | https://doi.org/10.1038/s41408-023-00960-1 |
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