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Graft-versus-host Disease

Active thrombopoiesis is associated with worse severity and activity of chronic GVHD

Bone Marrow Transplantation volume 48, pages 1569–1573 (2013)Cite this article

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Abstract

Chronic GVHD (cGVHD) is a major complication of allogeneic hematopoietic SCT. Post transplant thrombocytopenia in patients with cGVHD has been associated with poor outcome and its etiology is unclear. We investigated whether thrombopoiesis, assessed via measurement of the absolute immature platelet number (AIPN) in the blood, is impaired in cGVHD, and whether the level of thrombopoiesis correlates with the severity and activity of cGVHD as assessed via the National Institutes of Health (NIH) organ scoring system. We used a cohort of 110 well-characterized cGVHD patients, including 83 (75%) with severe cGVHD per NIH global score. Higher AIPN was associated with active therapeutic intent (P=0.026), lower Karnofsky score (P=0.0013), worse joint/fascia cGVHD (P=0.0005) and worse skin cGVHD (P=0.0044). AIPN correlated with platelet counts and was not correlated with ANC, WBC, C-reactive protein (CRP), absolute lymphocyte count (ALC), albumin, total and average NIH scores, or number of prior systemic therapies. AIPN values for cGVHD patients substantially overlapped those of the normal population. Higher AIPN, as marker of active thrombopoiesisis, was associated with worse severity and activity of cGVHD, especially skin and joints/fascia manifestations. Among patients with stable moderate or severe cGVHD, there was no evidence of hypoproduction of platelets. Future studies should further investigate the role of thrombopoiesis in cGVHD.

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References

  1. Pulanic D, Lozier JN, Pavletic SZ . Thrombocytopenia and hemostatic disorders in chronic graft versus host disease. Bone Marrow Transplant 2009; 44: 393–403.

    Article  CAS  Google Scholar 

  2. Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y et al. Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood 2010; 115: 5401–5411.

    Article  CAS  Google Scholar 

  3. Yamazaki R, Kuwana M, Mori T, Okazaki Y, Kawakami Y, Ikeda Y et al. Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant 2006; 38: 377–384.

    Article  CAS  Google Scholar 

  4. Hayashi S, Oshida M, Kiyoi T, Todokoro S, Kashiwagi H, Honda S et al. Comparison of reticulated platelet count with plasma glycocalicin concentration as a marker of platelet turnover in patients with thrombocytopenic disorders. RinshoKetsueki 2000; 41: 705–711.

    CAS  Google Scholar 

  5. Emmons RV, Reid DM, Cohen RL, Meng G, Young NS, Dunbar CE et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood 1996; 87: 4068–4071.

    CAS  PubMed  Google Scholar 

  6. Bat T, Leitman SF, Calvo KR, Chauvet D, Dunbar CE . Measurement of the absolute immature platelet number reflects marrow production and is not impacted by platelet transfusion. Transfusion 2012; 53: 1201–1204.

    Article  Google Scholar 

  7. Filipovich AH, Weisdorf D, Pavletic SZ, Socie G, Wingard JR, Lee SJ et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft - versus - host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  Google Scholar 

  8. Grkovic L, Baird K, Steinberg SM, Williams KM, Pulanic D, Cowen EW et al. Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity. Leukemia 2012; 26: 633–643.

    Article  CAS  Google Scholar 

  9. Walters J, Garrity P . Performance evaluation of the Sysmex XE-2100 hematology analyzer. Lab Hematol 2000; 6: 83–92.

    CAS  Google Scholar 

  10. Hollander M, Wolfe DA . Non-parametric Statistical Methods 2nd edn. John Wiley and Sons, Inc:: New York, NY, 1999 pp 189–269.

    Google Scholar 

  11. Cho BS, Min CK, Eom KS, Kim YJ, Kim HJ, Lee S et al. Feasibility of NIH consensus criteria for chronic graft-versus-host disease. Leukemia 2009; 23: 78–84.

    Article  Google Scholar 

  12. Ito H . Anti-interleukin-6 therapy for Crohn’s disease. Curr Pharm Des 2003; 9: 295–305.

    Article  CAS  Google Scholar 

  13. Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001; 98: 2720–2725.

    Article  CAS  Google Scholar 

  14. Akpek G, Zahurak ML, Piantadosi S, Margolis J, Doherty J, Davidson R et al. Development of a prognostic model for grading chronic graft-versus-host disease. Blood 2001; 97: 1219–1226.

    Article  CAS  Google Scholar 

  15. Akpek G, Lee SJ, Flowers ME, Pavletic SZ, Arora M, Lee S et al. Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study. Blood 2003; 102: 802–809.

    Article  CAS  Google Scholar 

  16. Pavletic SZ, Smith LM, Bishop MR, Lynch JC, Tarantolo SR, Vose JM et al. Prognostic factors of chronic graft-versus-host disease after allogeneic blood stem-cell transplantation. Am J Hematol 2005; 78: 265–274.

    Article  Google Scholar 

  17. Kuzmina Z, Eder S, Böhm A, Pernicka E, Vormittag L, Kalh P et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study. Leukemia 2012; 26: 746–756.

    Article  CAS  Google Scholar 

  18. Pérez-Simón JA, Afram G, Martino R, Piñana JL, Caballero-Velazquez T, Ringden O et al. Evaluation of prognostic factors among patients with chronic graft-versus-host disease. Haematologica 2012; 97: 1187–1195.

    Article  Google Scholar 

  19. Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001; 98: 2720–2725.

    Article  CAS  Google Scholar 

  20. Chen X, Vodanovic-Jankovic S, Johnson B, Keller M, Komorowski R, Drobyski WR . Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease. Blood 2007; 110: 3804–3813.

    Article  CAS  Google Scholar 

  21. Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP . Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007; 139: 351–362.

    Article  CAS  Google Scholar 

  22. Terui T, Niitsu Y, Mahara K, Fujisaki Y, Urushizaki Y, Mogi Y et al. The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood 1990; 75: 1540–1548.

    CAS  PubMed  Google Scholar 

  23. Dominietto A, Raiola AM, Van Lint MT, Lamparelli T, Gualandi F, Berisso G et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 2001; 112: 219–227.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    T Bat, R Childs, A J Barrett, M Battiwalla & C E Dunbar

  2. Biostatistics and Data Management Section, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    S M Steinberg

  3. Department of Laboratory Medicine, Hematology Section, National Institutes of Health Clinical Center, Bethesda, MD, USA

    K R Calvo

  4. Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    K Baird

  5. Experimental Immunology and Transplantation Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

    D Zhang, D Pulanic & S Z Pavletic

  6. Division of Hematology, Department of Internal Medicine, Clinical Hospital Center Zagreb, Zagreb, Croatia

    D Pulanic

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  1. T Bat
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  2. S M Steinberg
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  3. R Childs
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  4. K R Calvo
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  9. D Pulanic
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  10. C E Dunbar
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  11. S Z Pavletic
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Correspondence to C E Dunbar.

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Bat, T., Steinberg, S., Childs, R. et al. Active thrombopoiesis is associated with worse severity and activity of chronic GVHD. Bone Marrow Transplant 48, 1569–1573 (2013). https://doi.org/10.1038/bmt.2013.95

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