Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

Porrata, Luis F.; Markovic, Svetomir N.

doi:https://doi.org/10.3814/2010/812304

SRX Medicine

On this page

Abstract References Copyright Related Articles

Review Article | Open Access

Volume 2010 | Article ID 812304 | https://doi.org/10.3814/2010/812304

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

Luis F. Porrata¹and Svetomir N. Markovic¹

Received24 Nov 2009

Revised12 Jan 2010

Accepted27 Jan 2010

Published21 Feb 2010

Abstract

The role of host immunity in cancer clinical outcomes has been wellestablished in animal models. In humans, the impact of the immune system as a therapeutic maneuver to treat malignancies has been proven by the development of graft-versus-tumor effect observed in the allogeneic stem cell transplantation. However, with few notable exceptions, no definitive conclusions have been reached as to the role of host immunity in humans and its impact on cancer outcomes. This article reviews the clinical evidence of how human immunity can affect cancer clinical outcomes using the absolute lymphocyte count as a surrogate maker of host immune competence.

References

P. Ehrlich, “Ueber den jetzigen Stand der Karzinomforschung,” Nederlands Tijdschrift voor Geneeskunde, vol. 5, pp. 273–290, 1909.
View at: Google Scholar
M. Burnet, “Cancer; a biological approach. I. The processes of control,” British Medical Journal, vol. 1, no. 5022, pp. 779–786, 1957.
View at: Google Scholar
M. S. Block and S. N. Markovic, “The tumor/immune interface: clinical evidence of cancer immunosurveillance, immunoediting and immunosubversion,” American Journal of Immunology, vol. 5, no. 1, pp. 29–49, 2009.
View at: Google Scholar
Y. Oki, K. Yamamoto, H. Kato et al., “Low absolute lymphocyte count is a poor prognostic marker in patients with diffuse large B-cell lymphoma and suggests patients' survival benefit from rituximab,” European Journal of Haematology, vol. 81, no. 6, pp. 448–453, 2008.
View at: Publisher Site | Google Scholar
M. C. Cox, I. Nofroni, L. Ruco et al., “Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma,” Leukemia and Lymphoma, vol. 49, no. 9, pp. 1745–1751, 2008.
View at: Publisher Site | Google Scholar
M. C. Cox, I. Nofroni, G. Laverde et al., “Absolute lymphocyte count is a prognostic factor in diffuse large B-cell lymphoma,” British Journal of Haematology, vol. 141, no. 2, pp. 265–268, 2008.
View at: Publisher Site | Google Scholar
M. Siddiqui, K. Ristow, S. N. Markovic et al., “Absolute lymphocyte count predicts overall survival in follicular lymphomas,” British Journal of Haematology, vol. 134, no. 6, pp. 596–601, 2006.
View at: Publisher Site | Google Scholar
I. Ray-Coquard, C. Cropet, M. Van Glabbeke et al., “Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas,” Cancer Research, vol. 69, no. 13, pp. 5383–5391, 2009.
View at: Publisher Site | Google Scholar
H. Ege, M. A. Gertz, S. N. Markovic et al., “Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective study,” British Journal of Haematology, vol. 141, no. 6, pp. 792–798, 2008.
View at: Publisher Site | Google Scholar
N. L. Jacobs, S. G. Holtan, L. F. Porrata, S. N. Markovic, A. Tefferi, and D. P. Steensma, “Low absolute lymphocyte count (ALC) at diagnosis is an IPSS-independent predictor of poorer survival in myelodysplastic syndrome (MDS),” Blood, vol. 112, 2008, abstract 3633.
View at: Google Scholar
A. E. Papatestas, G. J. Lesnick, G. Genkins, and A. H. Aufses Jr., “The prognostic significance of peripheral lymphocyte counts in patients with breast carcinoma,” Cancer, vol. 37, no. 1, pp. 164–168, 1976.
View at: Google Scholar
J. S. Blake-Mortimer, S. E. Sephton, R. W. Carlson, D. Stites, and D. Spiegel, “Cytotoxic T lymphocyte count and survival time in women with metastatic breast cancer,” Breast Journal, vol. 10, no. 3, pp. 195–199, 2004.
View at: Publisher Site | Google Scholar
P. Fogar, C. Sperti, D. Basso et al., “Decreased total lymphocyte counts in pancreatic cancer: an index of adverse outcome,” Pancreas, vol. 32, no. 1, pp. 22–28, 2006.
View at: Google Scholar
A. Fukunaga, M. Miyamoto, Y. Cho et al., “CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma,” Pancreas, vol. 28, no. 1, pp. 26–31, 2004.
View at: Google Scholar
A. Riesco, “Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils,” Cancer, vol. 25, no. 1, pp. 135–140, 1970.
View at: Google Scholar
Y. T. N. Lee, “Peripheral lymphocyte count and subpopulations of T and B lymphocytes in benign and malignant diseases,” Surgery, Gynecology and Obstetrics, vol. 144, no. 3, pp. 435–450, 1977.
View at: Google Scholar
F. Marti, N. Pardo, M. Peiro et al., “Progression of natural immunity during one-year treatment of residual disease in neuroblastoma patients with high doses of interleukin-2 after autologous bone marrow transplantation,” Experimental Hematology, vol. 23, no. 14, pp. 1445–1452, 1995.
View at: Google Scholar
D. Behl, L. F. Porrata, S. N. Markovic et al., “Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia,” Leukemia, vol. 20, no. 1, pp. 29–34, 2006.
View at: Publisher Site | Google Scholar
G. De Angulo, C. Yuen, S. L. Palla, P. M. Anderson, and P. A. Zweidler-McKay, “Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies,” Cancer, vol. 112, no. 2, pp. 407–415, 2008.
View at: Publisher Site | Google Scholar
P. Lissoni, F. Brivio, L. Fumagalli et al., “Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastic solid tumors,” International Journal of Biological Markers, vol. 19, no. 2, pp. 135–140, 2004.
View at: Google Scholar
G. De Angulo, M. Hernandez, J. Morales-Arias et al., “Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma,” Journal of Pediatric Hematology/Oncology, vol. 29, no. 1, pp. 48–52, 2007.
View at: Publisher Site | Google Scholar
S. G. DuBois, K. Elterman, and H. E. Grier, “Early lymphocyte recovery in Ewing sarcoma,” Journal of Pediatric Hematology/Oncology, vol. 29, no. 5, pp. 351–352, 2007.
View at: Publisher Site | Google Scholar
L. F. Porrata, K. Ristow, T. M. Habermann, T. E. Witzig, D. J. Inwards, and S. N. Markovic, “Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B-cell lymphoma,” American Journal of Hematology, vol. 84, no. 2, pp. 93–97, 2009.
View at: Publisher Site | Google Scholar
D. R. Choi, D. H. Yoon, H. J. Ahn et al., “Significance of absolute lymphocyte count at relapse as a prognostic factor in patients with T-cell non-Hodgkin's lymphoma,” Blood, vol. 144, 2009, abstract 2939.
View at: Google Scholar
I. Ray-Coquard, H. Ghesquière, T. Bachelot et al., “Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas,” British Journal of Cancer, vol. 85, no. 6, pp. 816–822, 2001.
View at: Publisher Site | Google Scholar
A. J. Barrett and B. N. Savani, “Does chemotherapy modify the immune surveillance of hematological malignancies?” Leukemia, vol. 23, no. 1, pp. 53–58, 2009.
View at: Publisher Site | Google Scholar
D. Decaudin, G. Des Guetz, C. Mathiot et al., “Absolute lymphocyte count as a predictive factor for response to monoclonal anti-CD20 antibody therapy,” Annals of Oncology, vol. 14, no. 1, pp. 171–172, 2003.
View at: Publisher Site | Google Scholar
D. Behl, K. Ristow, S. N. Markovic et al., “Absolute lymphocyte count predicts therapeutic efficacy of rituximab therapy in follicular lymphomas,” British Journal of Haematology, vol. 137, no. 5, pp. 409–415, 2007.
View at: Publisher Site | Google Scholar
T. E. Witzig, “Radioimmunotherapy for B-cell non-Hodgkin lymphoma,” Best Practice and Research: Clinical Haematology, vol. 19, no. 4, pp. 655–668, 2006.
View at: Publisher Site | Google Scholar
L. F. Porrata, K. Ristow, T. E. Witzig et al., “Absolute lymphocyte count predicts therapeutic efficacy and survival at the time of radioimmunotherapy in patients with relapsed follicular lymphomas,” Leukemia, vol. 21, no. 12, pp. 2554–2556, 2007.
View at: Publisher Site | Google Scholar
D. Zhu, L. G. Corral, Y. W. Fleming, and B. Stein, “Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation,” Cancer Immunology, Immunotherapy, vol. 57, no. 12, pp. 1849–1859, 2008.
View at: Publisher Site | Google Scholar
T. E. Witzig, C. B. Reeder, J. Polikoff et al., “Initial results from an international study in relapse/refractory aggressive non-Hodgkin's lymphoma to confirm the activity, safety and criteria for predicting response to lenalidomide monotherapy,” Blood, vol. 110, 2007, abstract 2572.
View at: Google Scholar
P. H. Wiernik, I. S. Lossos, J. M. Tuscano et al., “Lenalidomide response in relapsed/refractory aggressive non-Hodgkin's lymphoma is related to tumor burden and time from rituximab treatment,” Blood, vol. 110, 2007, abstract 2565.
View at: Google Scholar
S. Mustjoki, T. Lundán, S. Knuutila, and K. Porkka, “Appearance of bone marrow lymphocytosis predicts an optimal response to imatinib therapy in patients with chronic myeloid leukemia,” Leukemia, vol. 21, no. 11, pp. 2363–2368, 2007.
View at: Publisher Site | Google Scholar
D. W. H. Barnes, M. J. Corp, J. F. Loutit, and F. E. Neal, “Treatment of murine leukemia with X-rays and homologous bone marrow. Preliminary communication,” British Medical Journal, vol. 2, pp. 626–627, 1956.
View at: Google Scholar
L. F. Porrata and S. N. Markovic, “Timely reconstitution of immune competence affects clinical outcome following autologous stem cell transplantation,” Clinical and Experimental Medicine, vol. 4, no. 2, pp. 78–85, 2004.
View at: Publisher Site | Google Scholar
R. Powles, S. Singhal, J. Treleaven, S. Kulkarni, C. Horton, and J. Mehta, “Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation,” Blood, vol. 91, no. 9, pp. 3481–3486, 1998.
View at: Google Scholar
Z. S. Pavletic, S. S. Joshi, S. J. Pirruccello et al., “Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies,” Bone Marrow Transplantation, vol. 21, no. 1, pp. 33–41, 1998.
View at: Google Scholar
L. F. Porrata, M. A. Gertz, D. J. Inwards et al., “Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma,” Blood, vol. 98, no. 3, pp. 579–585, 2001.
View at: Publisher Site | Google Scholar
L. F. Porrata, M. R. Litzow, A. Tefferi et al., “Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia,” Leukemia, vol. 16, no. 7, pp. 1311–1318, 2002.
View at: Publisher Site | Google Scholar
L. F. Porrata, D. J. Inwards, I. N. Micallef, S. M. Ansell, S. M. Geyer, and S. N. Markovic, “Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease,” British Journal of Haematology, vol. 117, no. 3, pp. 629–633, 2002.
View at: Publisher Site | Google Scholar
L. F. Porrata, M. A. Gertz, M. R. Litzow et al., “Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis,” Clinical Cancer Research, vol. 11, no. 3, pp. 1210–1218, 2005.
View at: Google Scholar
C. Joao, L. F. Porrata, D. J. Inwards et al., “Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma,” Bone Marrow Transplantation, vol. 37, no. 9, pp. 865–871, 2006.
View at: Publisher Site | Google Scholar
L. F. Porrata, J. N. Ingle, M. R. Litzow, S. Geyer, and S. N. Markovic, “Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer,” Bone Marrow Transplantation, vol. 28, no. 9, pp. 865–871, 2001.
View at: Publisher Site | Google Scholar
G. Ferrandina, L. Pierelli, A. Perillo et al., “Lymphocyte recovery in advanced ovarian cancer patients after high-dose chemotherapy and peripheral blood stem cell plus growth factor support: clinical implications,” Clinical Cancer Research, vol. 9, no. 10, pp. 195–200, 2003.
View at: Google Scholar
M. R. Boulassel, A. L. Herr, M. D. deB Edwardes et al., “Early lymphocyte recovery following autologous peripheral stem cell transplantation is associated with better survival in younger patients with lymphoproliferative disorders,” Hematology, vol. 11, no. 3, pp. 165–170, 2006.
View at: Publisher Site | Google Scholar
H. Kim, H.-J. Sohn, S. Kim, J.-S. Lee, W.-K. Kim, and C. Suh, “Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma,” Bone Marrow Transplantation, vol. 37, no. 11, pp. 1037–1042, 2006.
View at: Publisher Site | Google Scholar
Y. Nieto, E. J. Shpall, I. K. McNiece et al., “Prognostic analysis of early lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with an autologous hematopoietic progenitor cell transplant,” Clinical Cancer Research, vol. 10, no. 15, pp. 5076–5086, 2004.
View at: Publisher Site | Google Scholar
H. Kim, H.-J. Sohn, S.-E. Kim et al., “Lymphocyte recovery as a positive predictor of prolonged survival after autologous peripheral blood stem cell transplantation in T-cell non-Hodgkin's lymphoma,” Bone Marrow Transplantation, vol. 34, no. 1, pp. 43–49, 2004.
View at: Publisher Site | Google Scholar
L. N. Gordan, M. W. Sugrue, J. W. Lynch, K. D. Williams, S. A. Khan, and J. S. Moreb, “Correlation of early lymphocyte recovery and progression-free survival after autologous stem-cell transplant in patients with Hodgkin's and non-Hodgkin's lymphoma,” Bone Marrow Transplantation, vol. 31, no. 11, pp. 1009–1013, 2003.
View at: Publisher Site | Google Scholar
L. F. Porrata, D. J. Inwards, S. M. Ansell et al., “Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study,” Biology of Blood and Marrow Transplantation, vol. 14, no. 7, pp. 807–816, 2008.
View at: Publisher Site | Google Scholar
A. Plonquet, C. Haioun, J.-P. Jais et al., “Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2-3 diffuse large B-cell lymphoma,” Annals of Oncology, vol. 18, no. 7, pp. 1209–1215, 2007.
View at: Publisher Site | Google Scholar
B.-Q. Zhu, S.-W. Ju, and Y.-Q. Shu, “CD137 enhances cytotoxicity of CD3+CD56+ cells and their capacities to induce CD4+ Th1 responses,” Biomedicine and Pharmacotherapy, vol. 63, no. 7, pp. 509–516, 2009.
View at: Publisher Site | Google Scholar
R. Houot, M. J. Goldstein, H. E. Kohrt et al., “Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by T-reg depletion,” Blood, vol. 114, no. 16, pp. 3431–3438, 2009.
View at: Publisher Site | Google Scholar
S. Mittal, N. A. Marshall, L. Duncan, D. J. Culligan, R. N. Barker, and M. A. Vickers, “Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma,” Blood, vol. 111, no. 11, pp. 5359–5370, 2008.
View at: Publisher Site | Google Scholar
Z. Z. Yang and S. M. Ansell, “The role of T-reg cells in the cancer immunological response,” American Journal of Immunology, vol. 5, no. 10, pp. 17–28, 2009.
View at: Google Scholar
F. Balkwill and A. Mantovani, “Inflammation and cancer: back to Virchow?” The Lancet, vol. 357, no. 9255, pp. 539–545, 2001.
View at: Publisher Site | Google Scholar
L. M. Coussens and Z. Werb, “Inflammation and cancer,” Nature, vol. 420, no. 6917, pp. 860–867, 2002.
View at: Publisher Site | Google Scholar
A. Mantovani, P. Allavena, A. Sica, and F. Balkwill, “Cancer-related inflammation,” Nature, vol. 454, no. 7203, pp. 436–444, 2008.
View at: Publisher Site | Google Scholar
S. Teramukai, T. Kitano, Y. Kishida et al., “Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03,” European Journal of Cancer, vol. 45, no. 11, pp. 1950–1958, 2009.
View at: Publisher Site | Google Scholar
J. Atzpodien, P. Royston, T. Wandert et al., “Metastatic renal carcinoma comprehensive prognostic system,” British Journal of Cancer, vol. 88, no. 3, pp. 348–353, 2003.
View at: Publisher Site | Google Scholar
H. Schmidt, S. Suciu, C. J. A. Punt et al., “Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer stage IV melanoma: results of the EORTC 18951 biochemotherapy trial,” Journal of Clinical Oncology, vol. 25, no. 12, pp. 1562–1569, 2007.
View at: Publisher Site | Google Scholar
K. M. Sarraf, E. Belcher, E. Raevsky, A. G. Nicholson, P. Goldstraw, and E. Lim, “Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer,” Journal of Thoracic and Cardiovascular Surgery, vol. 137, no. 2, pp. 425–428, 2009.
View at: Publisher Site | Google Scholar
Y. Nakahara, Y. Mochiduki, Y. Miyamoto, Y. Nakahara, and Y. Katsura, “Prognostic significance of the lymphocyte-to-neutrophil ratio in percutaneous fine-needle aspiration biopsy specimens of advanced nonsmall cell lung carcinoma,” Cancer, vol. 104, no. 6, pp. 1271–1280, 2005.
View at: Publisher Site | Google Scholar
F. J. Esteva and L. Pusztai, “Optimizing outcomes in HER2-positive breast cancer: the molecular rationale,” Oncology, vol. 19, no. 13, supplement 5, pp. 5–16, 2005.
View at: Google Scholar
L. F. Porrata, “Clinical evidence of autologous graft versus tumor effect,” American Journal of Immunology, vol. 5, no. 1, pp. 1–7, 2009.
View at: Google Scholar
C. Joao, L. F. Porrata, E. A. Burgstaler et al., “Immunologic autograft engineering by manipulation of apheresis machine collection settings,” Biology of Blood and Marrow Transplantation, vol. 12, no. 2, supplement 1, p. 105, 2006, abstract 298.
View at: Google Scholar

Copyright

Copyright © 2010 Luis F. Porrata and Svetomir N. Markovic. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

997

Downloads

0

Citations