Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer
Cancer Research Journal
Volume 3, Issue 3, May 2015, Pages: 47-51
Received: Apr. 13, 2015; Accepted: Apr. 25, 2015; Published: May 12, 2015
Views 3683      Downloads 124
Alexei N. Shoutko, Laboratory of the development of radiation therapy methods, Federal Scientific Centre for Radiology and Surgical Technologies, Saint-Petersburg, Russian Federation
Ludmila E. Yurkova, Division of Gynecologic Oncology, Federal Scientific Centre for Radiology and Surgical Technologies, Saint-Petersburg, Russian Federation
Kseniya S. Borodulya, Division of Gynecologic Oncology, Federal Scientific Centre for Radiology and Surgical Technologies, Saint-Petersburg, Russian Federation
Ludmila P. Ekimova, Laboratory of the development of radiation therapy methods, Federal Scientific Centre for Radiology and Surgical Technologies, Saint-Petersburg, Russian Federation
Article Tools
Follow on us
The relationship between 5-year survival and the mean number of circulating lymphocytes during 1 month after beginning a combined therapy was investigated in 175 patients with advanced epithelial ovarian cancer to understand why myelosuppression caused by a cytotoxic treatment is almost inseparable from its benefit. Patients received a combined therapy consisting of primary cytoreductive surgery followed by different systemic treatments according to three schemes: conventional chemotherapy with cisplatinum and cyclophosphanum (CP), conventional chemotherapy with paclitaxel and carboplatinum (TP), or lower-half body irradiation (LHBI). The TP scheme included premedication with dexamethasone. The LHBI involve irradiation with a total dose of 9 Gy (3 Gy daily) in patients with primary disease. LHBI with a total dose of 1 Gy (0.1 Gy daily) was used for patients with primary disease or relapse. The LHBI treatment included five final courses of thiophosphamide/5-fluorouracil for patients with primary cancer or conventional local radiotherapy up to a total dose of 30 Gy (2 Gy daily) for relapsed patients. Survival curves were analyzed by exponential approximation, and 5-year exponential mortality rates were calculated. The mortality rates were compared with the relative decline in the mean number of circulating lymphocytes after 1 month of therapy. If pretreatment lymphocytopenia did not exceed 0.7 109 cells /L, a linear dependency of the exponential death rate from the relative deviation of cells in the range of 1.16 to 0.7 (p < 0.001) was observed. The inevitable side effect of cytotoxic cancer therapy in the form of lymphocytopenia sheds doubt on the actual existence of effective antineoplastic immunity; however, it provides a logical background of the morphogenic function of some circulating mononuclear cells in relation to proliferating tissues, including malignant tissues.
Cytotoxic Therapy, Death Rates, Lymphocytopenia, Myelosuppression, Ovarian Cancer, Survival
To cite this article
Alexei N. Shoutko, Ludmila E. Yurkova, Kseniya S. Borodulya, Ludmila P. Ekimova, Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer, Cancer Research Journal. Vol. 3, No. 3, 2015, pp. 47-51. doi: 10.11648/j.crj.20150303.11
U.S. Department of Health and Human Services, National Institute of Health, National Cancer Institute.”Blood/bone marrow,” in: Common terminology criteria for adverse events (CTCAE)/Version 3.0, AMGEN Oncology, p.4, August 2006.。
G. Beretta, Cancer chemotherapy regimens. Milano, Italy, Farmitalia Carlo Erba, 1983.
J. L. Liesveld, Ph. Rubin, and L.S. Constine, “Hematopoietic system”, in: Adverse late effects of cancer treatment. V.2: Normal tissue specific sites and systems, Eds. Ph. Rubin, L. S. Constine, L. B. Marks, Heidelberg, Germany, Springer Verlag, 2014, pp. 623-656. doi: 10.1007/978-3-540-75863-1.
M. Akiyama and Y. Kusunoki, “Immune function,” in: Effects of A-bomb radiation on the human body, I. Shigematsu, C. Ito, N. Kamada, M. Akiyama, H. Sasaki, B. Harrison, Eds. Tokyo, Japan, Harwood academic publishers, Bunkodo Co.,1995, pp. 290-306.
A. Shoutko and N. Shatinina, “Chronic cancer - could its be?,” COHERENCE. International Journal of Integrated Medicine, 1998. 2. pp. 36-40.
A. N. Shoutko, L. P. Ekimova, M. J. Vasilyeva, and N. N. Shatinina, ”Tissue factors involved in cancer induction”, in: High level of natural radiation and radon areas:radiation dose and health effects, part 2, J. Peter, G. Schnider, A. Bayer, Eds., Bundesamt fur Strahlenscutz Schriften, 2002, Proceedings of 5th international conference on high levels of natural radiation and radon areas held in Munich, Germany on September 4 to 7, 2000. pp. 467–470.‎
A. Shoutko, I. Akushevich, L. Ekimova, M. Karamullin, A. Yashin, “The terminal exhaustion of hematopoietic potentiality as universal cause of death,” Abstracts book of 38th Annual Meeting of the European Radiation Research Society held in Stockholm, Sweden on September 5 to 9, 2010, p. 187.
C. Drapeau, Cracking the stem cell code: demystifying the most dramatic scientific breakthrough of our times. Hillsboro, Or, Goodwill Books USA, Sutton Hart Press / 1st. ed., 2010.
W. Nothdurft, “Bone Marrow”, in: Radiopathology of organs and tissues, E.Scherer, C. Streffer, and K.Trott, Eds., Berlin, Germany, Springer-Verlag, 1991, pp. 113-169.
Curve fitting project -, pp. 1-4.
J. L. Loveland, (2011).Mathematical justification of introductory hypothesis tests and development of reference materials (M.Sc. (Mathematics). Utah State University, Retrieved April/2013.
F. Khalil, H. Cualing, J. Cogburn, and L. Miles, “The criteria for bone marrow recovery postmyelosuppressive therapy for acute myelogenous leukemia: a quantitative study,” Arch Pathol Lab Med, vol. 131(8), pp. 1281–1289, August 2007. PMID:17683190
T. M. Fliedner D. and H. Graessle, “Hematopoietic cell renewal systems: mechanisms of coping and failing after chronic exposure to ionizing radiation,” Radiat Environ Biophys, vol. 47(1), pp. 63–69, February 2008. doi:10.1007/s00411-007-0148-6
W. J. Hou , J. H. Guan, Q. Dong, Y. H. Han, and R. Zhang, “Dexamethasone inhibits the effect of paclitaxel on human ovarian carcinoma xenografts in nude mice,” Rev Med Pharmacol Sci, vol.17(21), pp. 2902-2908, Nov. 2013. PMID: 24254559
M. H. Magee, R. A. Blum, C. D. Lates, and W. J. Jusko, “Pharmacokinetic/pharmacodynamic model for prednisolone inhibition of whole blood lymphocyte proliferation,” Br J Clin Pharmacol, vol. 53(5), pp. 474–484, May 2002. doi: 10.1046/j.1365-2125.2002.01567.x PMCID: PMC1874371
R. W. Jang, V. B. Caraiscos, N. Swami, S. Banerjee, E. Mak, E. Kaya, G. Rodin, J. Bryson, J. Z. Ridley, L. W. Le, and C. Zimmermann, “Simple prognostic model for patients with advanced cancer based on performance status,” J of On Practice, vol. 10(5), pp. e335-e341, September 2014. doi: 10.1200/JOP.2014.001457
A. Shoutko, L. Ekimova, V. Mus, and V. Sokurenko, “Fluctuations of CD34 cells number in blood of cancer patients during final year of life,” Medical and Health Science Journal (MHSJ)/Acad. Publ. Platform, vol.13(4), pp. 7–13, December 2012.
A N. Shoutko and L P. Ekimova, “The impact of middle age on the viability of patients with nonmalignant and malignant diseases,” Cancer Research Journal, vol. 2(6), pp. 114-120, December 2014. doi: 10.11648/j.crj.20140206.14
A.N. Shoutko and L.P. Ekimova, “Abnormal tissue proliferation and life span variability in chronically irradiated dogs,” Radiat Environ Biophys, vol. 53(1), pp. 65-72, March 2014. doi: 10.1007/s00411-013-0504-7
J. Hur, H.-M. Yang, C.-H. Yoon, C.-S. Lee, K.-W. Park, J.-H. Kim, T.-Y. Kim, J.-Y. Kim, H.-J. Kang, I.-H. Chae, B.-H. Oh, Y.-B. Park, and H.-S. Kim, “Identification of a novel role of T cells in postnatal vasculogenesis. Characterization of endothelial progenitor cell colonies,” Circulation, vol. 116(15), pp. 1671-1682, October 2007. PMID:17909106
V. Cumar, A K Abbas, N Fausto, and J Astar, “Tissue renewal, regeneration, and repair,” in: Robins and Cotran pathologic basis of disease, 8th edition by V Sounders Elsevier, Philadelphia, PA, USA, 2010, pp.79-110.
L. Zucco, Q. Zhang, M. A. Kuliszewski, I. Kandic, M. E. Faughnan, D. J. Stewart, M. J. Kutryk, “Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagictelangiectasia,” PLoS ONE, vol. 9(2), p. e89927, February 2014. doi: 10.1371/journal.pone.0089927. PMCID: PMC3934937
A. N. Shutko, I. V. Akushevich, L. P. Ekimova, V. F. Mus, B. P. Sokurenko, L. E. Yurkova, and K. S. Matiurin, “The mechanism of the antitumor effect of total/subtotal radiotherapy with non-tumoricidal doses of radiation,” Voprosy onkologii, 59(4), pp. 475-478, Okt-Dec 2013. PMID 24032222
A. N. Shoutko and L. P. Ekimova, “Lymphocytopenia can contribute in common benefit of cytotoxic therapy of cancer,” Inter-Medical, №3, pp. 5-13, September 2014.;
K. J. Propert and J. R. Anderson, “Assessing the effect of toxicity on prognosis: methods of analysis and interpretation,” JCO, vol. 6, pp. 868-870, month 1988.
K. S. Tewari, J.J. Java, T.A. Gatcliffe, M.A. Bookman, and B.J. Monk, “Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group,” Gynecol Oncol, vol.133(3), pp. 439-45, March 2014. PMID:24657300; doi: 10.1016/j.ygyno.2014.03.013. Epub 2014 20.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186