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. 2020 May 7;135(19):1696-1703.
doi: 10.1182/blood.2019003347.

Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis

Lukas Ronner  1 , Nikolai Podoltsev  2 , Jason Gotlib  3 , Mark L Heaney  4 , Andrew T Kuykendall  5 , Casey O'Connell  6 , Jamile Shammo  7 , Angela G Fleischman  8 , Robyn M Scherber  9 , Ruben Mesa  9 , Abdulraheem Yacoub  10 , Cecelia Perkins  3 , Shelby Meckstroth  11 , Lindsey Behlman  2 , Matthew Chiaramonte  4 , Mahta Salehi  6 , Kimia Ziadkhanpour  1 , Hellen Nguyen  8 , Olivia Siwoski  10 , Annie Kwok Hung  9 , Michelle Janania Martinez  9 , Jenny Nguyen  8 , Sagar Patel  6 , Revathi Kollipara  7 , Ami Dave  7 , Megan Randall  7 , Michael Grant  7 , Mitchell Harrison  7 , Paola Fernandez Soto  7 , Douglas Tremblay  12 , Ronald Hoffman  12 , Erin Moshier  13 , John Mascarenhas  12
Affiliations

Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis

Lukas Ronner et al. Blood. .

Abstract

There are unresolved questions regarding the association between persistent leukocytosis and risk of thrombosis and disease evolution in polycythemia vera (PV), as much of the published literature on the topic does not appropriately use repeated-measures data or time-dependent modeling to answer these questions. To address this knowledge gap, we analyzed a retrospective database of 520 PV patients seen at 10 academic institutions across the United States. Taking hematologic laboratory data at ∼3-month intervals (or as available) for all patients for duration of follow-up, we used group-based trajectory modeling to identify latent clusters of patients who follow distinct trajectories with regard to their leukocyte, hematocrit, and platelet counts over time. We then tested the association between trajectory membership and hazard of 2 major outcomes: thrombosis and disease evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia. Controlling for relevant covariates, we found that persistently elevated leukocyte trajectories were not associated with the hazard of a thrombotic event (P = .4163), but were significantly associated with increased hazard of disease evolution in an ascending stepwise manner (overall P = .0002). In addition, we found that neither hematocrit nor platelet count was significantly associated with the hazard of thrombosis or disease evolution.

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Conflict of interest statement

Conflict-of-interest disclosure: J.M. has received clinical trial funding from Incyte, Roche, Novartis, Merck, CTI Biopharma, Janssen, and Promedior and has served as an advisor to Roche, Celgene, CTI Biopharma, PharmaEssentia, and Incyte. N.P. has consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, and Celgene; has received clinical trial funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI Biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals, and Kartos Therapeutics and grant funding from Celgene. M.H. has consulted for Incyte, AbbVie, Partner Therapeutics, Novartis, and Roche and has received research funding from Incyte, Roche, Blueprint, BMS, Constellation, Deciphera, Celgene, and CTI Biopharma. A.K. consults for and has received research funding from Janssen, honoraria from AbbVie and Incyte, and speaker’s fees from Celgene and is on the speakers bureau for Incyte. C.O. has received research funding from Astex and Genentech and is on the board of directors or advisory committees for Astex, Pfizer, BMS, and Shionogi. J.S. has consulted for Incyte, Celgene, Alexion, Sanofi, Novartis, and Otsuka Pharmaceutical; has received honoraria from Incyte, Celgene, Alexion, Sanofi, Novartis, and Otsuka and research funding from Incyte, Celgene, Alexion, Onconova, and Astex Pharma; is on the speakers bureau of Incyte, Celgene, Alexion, and Sanofi; and is a member of the board of directors for Apellis Pharmaceuticals. A.F. is on the speakers bureau for Incyte and Celgene. R.S. has consulted for Gilead and Incyte and is on the ad board for Blueprint Medicines. R.M. has consulted for Novartis, Sierra Oncology, and La Jolla Pharmaceutical and has received research funding from Celgene, Incyte, AbbVie, Samus Therapeutics, Genotech, Promedior, and CTI BioPharma. A.Y. is on the speakers bureau of Agios Pharmaceuticals, Incyte, Seattle Genetics, and Novartis; has received honoraria from Incyte; and has equity ownership in HylaPharm, Dynavax, Cara Therapeutics, and Ardelyx. R.H. receives research funding from Dompe, Novartis, Janssen, Scholar Rock, Summer Road, Elstar, and Merus. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Consort diagram showing inclusion of patients in the trajectory analysis.
Figure 2.
Figure 2.
GBTM-identified latent trajectories of hematologic laboratory values.
Figure 3.
Figure 3.
Kaplan-Meier plots of trajectories and outcomes of thrombosis and disease evolution.
See this image and copyright information in PMC

Comment in

  • To be, or not to be.
    Vannucchi AM. Vannucchi AM. Blood. 2020 May 7;135(19):1617-1618. doi: 10.1182/blood.2020005363. Blood. 2020. PMID: 32379876 No abstract available.

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