Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail: sychevskaya-ka@yandex.ru

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219


ABSTRACT

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Foley C, Mackey MC. Dynamic hematological disease: a review. J Math Biol. 2009;58(1–2):285–322. doi: 10.1007/s00285-008-0165-3.
  2. Morley AA. A neutrophil cycle in healthy individuals. Lancet. 1966;2(7475):1220–2. doi: 10.1016/s0140-6736(66)92303-8.
  3. Mackey MC, Glass L. Oscillation and chaos in physiological control systems. Science. 1977;197(4300):287–9. doi: 10.1126/science.267326.
  4. Mackey Cell kinetic status of haematopoietic stem cells. Cell Prolif. 2001;34(2):71–83. doi: 10.1046/j.1365-2184.2001.00195.x.
  5. Pujo-Menjouet L, Mackey MC. Contribution to the study of periodic chronic myelogenous leukemia. Compt Rend Biol. 2004;327(3):235–44. doi: 10.1016/j.crvi.2003.05.004.
  6. Schirm S, Engel C, Loeffler M, Scholz M. Modelling chemotherapy effects on granulopoiesis. BMC Syst Biol. 2014;8(1):138. doi: 10.1186/s12918-014-0138-7.
  7. Dale DC, Bolyard AA, Aprikyan A. Cyclic neutropenia. Semin Hematol. 2002;39(2):89–94. doi: 10.1053/shem.2002.31917.
  8. Levy EJ, Schetman D. Cyclic neutropenia. Arch Dermatol. 1961;84(3):429–33. doi: 10.1001/archderm.1961.01580150075012.
  9. Colijn C, Mackey MC. A mathematical model of hematopoiesis: II. Cyclical neutropenia. J Theor Biol. 2005;237(2):133–46. doi: 10.1016/j.jtbi.2005.03.034.
  10. Horwitz M, Benson KF, Person RE, et al. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999;23(4):433–6. doi: 10.1038/70544.
  11. Aprikyan AA, Liles WC, Rodger E, et al. Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia. Blood. 2001;97(1):147–53. doi: 10.1182/blood.v97.1.147.
  12. Horwitz MS, Corey SJ, Grimes HL, Tidwell T. ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematol Oncol Clin N Am. 2013;27(1):19-vii. doi: 10.1016/j.hoc.2012.10.004.
  13. Welte K, Zeidler C, Dale DC. Severe congenital neutropenia. Semin Hematol. 2006;43(3):189–95. doi: 10.1053/j.seminhematol.2006.04.004.
  14. Haurie C, Dale DC, Rudnicki R, Mackey MC. Modeling complex neutrophil dynamics in the grey collie. J Theor Biol. 2000;204(4):505–19. doi: 10.1006/jtbi.2000.2034.
  15. Horwitz MS, Duan Z, Korkmaz B, et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood. 2007;109(5):1817–24. doi: 10.1182/blood-2006-08-019166.
  16. Go RS. Idiopathic cyclic thrombocytopenia. Blood Rev. 2005;19(1):53–9. doi: 10.1016/j.blre.2004.05.001.
  17. Zhuge C, Mackey MC, Lei J. Origins of oscillation patterns in cyclical thrombocytopenia. J Theor Biol. 2019;462:432–45. doi: 10.1016/j.jtbi.2018.11.024.
  18. Apostu R, Mackey MC. Understanding cyclical thrombocytopenia: a mathematical modeling approach. J Theor Biol. 2008;251(2):297–316. doi: 10.1016/j.jtbi.2007.11.029.
  19. Colijn C, Mackey MC. A mathematical model of hematopoiesis–I. Periodic chronic myelogenous leukemia. J Theor Biol. 2005;237(2):117–32. doi: 10.1016/j.jtbi.2005.03.033.
  20. Fortin P, Mackey MC. Periodic chronic myelogenous leukaemia: spectral analysis of blood cell counts and aetiological implications. Br J Haematol. 1999;104(2):336–45. doi: 10.1046/j.1365-2141.1999.01168.x.
  21. Morley A, Stohlman F Jr. Cyclophosphamide-induced cyclical neutropenia. An animal model of a human periodic disease. N Engl J Med. 1970;282(12):643–6. doi: 10.1056/NEJM197003192821202.
  22. Kennedy Cyclic leukocyte oscillations in chronic myelogenous leukemia during hydroxyurea therapy. Blood. 1970;35(6):751–60. doi: 10.1182/blood.v35.6.751.751.
  23. Zhuge C, Lei J, Mackey MC. Neutrophil dynamics in response to chemotherapy and G-CSF. J Theor Biol. 2012;293:111–20. doi: 10.1016/j.jtbi.2011.10.017.
  24. Price TH, Chatta GS, Dale DC. Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood. 1996;88(1):335–40. doi: 10.1182/blood.V88.1.335.335.
  25. Chatta GS, Price TH, Allen RC, Dale DC. Effects of in vivo recombinant methionyl human granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers. Blood. 1994;84(9):2923–9. doi: 10.1182/blood.V84.9.2923.2923.
  26. Dancey JT, Deubelbeiss KA, Harker LA, Finch CA. Neutrophil kinetics in man. J Clin Invest. 1976;58(3):705–15. doi: 10.1172/JCI108517.
  27. Kerrigan DP, Castillo A, Foucar K, et al. Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration. Am J Clin Pathol. 1989;92(3):280–5. doi: 10.1093/ajcp/92.3.280.
  28. Hakansson L, Hoglund M, Jonsson UB, et al. Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion. Br J Haematol. 1997;98(3):603–11. doi: 10.1046/j.1365-2141.1997.2723093.x.
  29. Ohsaka A, Saionji K, Sato N, et al. Granulocyte colony-stimulating factor down-regulates the surface expression of the human leucocyte adhesion molecule-1 on human neutrophils in vitro and in vivo. Br J Haematol. 1993;84(4):574–80. doi: 10.1111/j.1365-2141.1993.tb03130.x.
  30. Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in Neutropenia. J Immunol. 2015;195(4):1341–9. doi: 10.4049/jimmunol.1500861.
  31. Dale DC, Bonilla MA, Davis MW, et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood. 1993;81(10):2496–502. doi: 10.1182/blood.V81.10.2496.2496.
  32. Shinjo K, Takeshita A, Ohnishi K, Ohno R. Granulocyte colony-stimulating factor receptor at various differentiation stages of normal and leukemic hematopoietic cells. Leuk Lymphoma. 1997;25(1–2):37–46. doi: 10.3109/10428199709042494.
  33. Clark OA, Lyman GH, Castro AA, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol. 2005;23(18):4198–214. doi: 10.1200/JCO.2005.05.645.
  34. Garcia-Carbonero R, Mayordomo JI, Tornamira MV, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst. 2001;93(1):31–8. doi: 10.1093/jnci/93.1.31.
  35. Maher DW, Lieschke GJ, Green M, et al. Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial. Ann Intern Med. 1994;121(7):492–501. doi: 10.7326/0003-4819-121-7-199410010-00004.
  36. Mitchell PL, Morland B, Stevens MC, et al. Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients. J Clin Oncol. 1997;15(3):1163–70. doi: 10.1200/JCO.1997.15.3.1163.
  37. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer. 1993;29A(3):319–24. doi: 10.1016/0959-8049(93)90376-q.
  38. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991;325(3):164–70. doi: 10.1056/NEJM199107183250305.
  39. Crawford J, Becker PS, Armitage JO, et al. Myeloid Growth Factors, Version 2.2017. NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(12):1520–41. doi: 10.6004/jnccn.2017.0175.
  40. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8–32. doi: 10.1016/j.ejca.2010.10.013.
  41. Crawford J, Caserta C, Roila F, ESMO Guidelines Working Group. Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications. Ann Oncol. 2010;21(Suppl 5):v248–v251. doi: 10.1093/annonc/mdq195.
  42. Lawrence SM, Corriden R, Nizet V. The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis. Microbiol Mol Biol Rev. 2018;82(1):e00057–17. doi: 10.1128/MMBR.00057-17.
  43. Murphy P. The Neutrophil. Boston: Springer; 1976. pp. 33–67.
  44. Lord BI, Bronchud MH, Owens S, et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo. Proc Natl Acad Sci USA. 1989;86(23):9499–503. doi: 10.1073/pnas.86.23.9499.
  45. Lie AK, Hui CH, Rawling T, et al. Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF. Bone Marrow Transplant. 1998;22(9):853–7. doi: 10.1038/sj.bmt.1701463.
  46. van Der Auwera P, Platzer E, Xu ZX, et al. Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim. Am J Hematol. 2001;66(4):245–51. doi: 10.1002/ajh.1052.
  47. Morstyn G, Campbell L, Souza LM, et al. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988;1(8587):667–72. doi: 10.1016/s0140-6736(88)91475-4.
  48. Shochat E, Rom-Kedar V, Segel LA. G-CSF control of neutrophils dynamics in the blood. Bull Math Biol. 2007;69(7):2299–338. doi: 10.1007/s11538-007-9221-1.
  49. Shochat E, Rom-Kedar V. Novel strategies for granulocyte colony-stimulating factor treatment of severe prolonged neutropenia suggested by mathematical modeling. Clin Cancer Res. 2008;14(20):6354–63. doi: 10.1158/1078-0432.CCR-08-0807.
  50. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9(1):181–218. doi: 10.1146/annurev-pathol-020712-164023.
  51. Hayes MP, Enterline JC, Gerrard TL, Zoon KC. Regulation of interferon production by human monocytes: requirements for priming for lipopolysaccharide-induced production. J Leuk Biol. 1991;50(2):176–81. doi: 10.1002/jlb.50.2.176.
  52. Boneberg EM, Hareng L, Gantner F, et al. Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ. Blood. 2000;95(1):270–6. doi: 10.1182/blood.V95.1.270.
  53. de Kleijn S, Langereis JD, Leentjens J, et al. IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS One. 2013;8(8):e72249. doi: 10.1371/journal.pone.0072249.
  54. Rutella S, Zavala F, Danese S, et al. Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance. J Immunol. 2005;175(11):7085– doi: 10.4049/jimmunol.175.11.7085.
  55. Ali N. Chimeric antigen T cell receptor treatment in hematological malignancies. Blood Res. 2019;54(2):81– doi: 10.5045/br.2019.54.2.81.
  56. Bais S, Bartee E, Rahman MM, et al. Oncolytic virotherapy for hematological malignancies. Adv Virol. 2012;2012:1–8. doi: 10.1155/2012/186512.
  57. Calton CM, Kelly KR, Anwer F, et al. Oncolytic Viruses for Multiple Myeloma Therapy. Cancers (Basel). 2018;10(6):198. doi: 10.3390/cancers10060198.
  58. Matveeva OV, Chumakov PM. Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses. Rev Med Virol. 2018;28(6):e2008. doi: 10.1002/rmv.2008.