The Effect of Curcumin (as Meriva) on Absolute Lymphocyte Count (ALC), NK Cells and T Cell Populations in Patients with Stage 0/1 Chronic Lymphocytic Leukemia

Terry Golombick^1*, Terrence H. Diamond¹, Arumugam Manoharan², Rajeev Ramakrishna²

¹Department of Endocrinology, St George Hospital, Sydney, Australia.
²Southern Sydney Haematology, University of Wollongong, Wollongong, Australia.

DOI: 10.4236/jct.2015.67061                

Abstract

Purpose: To determine the effect of curcumin (as Meriva) on absolute lymphocyte count (ALC), T cell populations and NK cells in patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) over a period of six months. Experimental Design: Twenty-one patients with significant lymphocytosis (>20 × 10⁹ lymphocytes/L) and stage 0/1 CLL were recruited into the study and received oral curcumin 2 grams/day. Blood samples were collected at baseline and at 2 monthly intervals for six months for full blood count, leukocyte surface antigens, liver function, serum biochemistry, immunoglobulins, CRP and ESR. A positive biologic response was defined as a reduction in the ALC of more than 20% from pre-treatment levels. Results: Four patients (20%) demonstrated more than 20% decrease in ALC, three of whom had lower ALC at the end of the study as compared to baseline. The decrease in ALC was accompanied by an increase in CD4, CD8 and NK cells. No demonstrable response was seen in seventeen patients (80%) who exhibited stable, fluctuating or increasing ALC during the study. Conclusion: A subgroup of stage 0/1 CLL patients may be responsive to curcumin therapy. The beneficial response appears to be immunomodulated.

Keywords

Stage 0/1 Chronic Lymphocytic Leukemia, Curcumin

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Shanafelt, T., Byrd, J., Call, T., et al. (2006) Intitial Management of Newly Diagnosed, Early Stage, Chronic Lymphocytic Leukemia. An Update for the Internist. Annals of Internal Medicine, 145, 435-447. http://dx.doi.org/10.7326/0003-4819-145-6-200609190-00007
[2]	Gonzalez-Rodriguez, A.P., Contesti, J., Huergo-Zapico, L., et al. (2010) Prognostic Significance of CD8 and CD4 T Cells in Chronic Lymphocytic Leukemia. Leukemia and Lymphoma, 51, 1829-1836. http://dx.doi.org/10.3109/10428194.2010.503820
[3]	Huergo-Zapico, L., Acebes-Huerta, A., Gonzalez-Rodriguez, A.P., et al. (2014) Expansion of NK Cells and Reduction of NKG2D Expression in Chronic Lymphocytic Leukemia. Correlation with Progressive Disease. PLOS ONE, 9, 1-9. http://dx.doi.org/10.1371/journal.pone.0108326
[4]	Dighiero, G., Maloum, K., Desablens, B., et al. (1998) Chlorambucil in Indolent Chronic Lymphocytic Leukemia: French Cooperative Group on Chronic Lymphocytic Leukemia. New England Journal of Medicine, 338, 1506-1514. http://dx.doi.org/10.1056/NEJM199805213382104
[5]	Shustik, C., Mick, R., Silver, R., et al. (1988) Treatment of Early Chronic Lymphocytic Leukemia: Intermittent Chlorambucil versus Observation. Hematological Oncology, 6, 7-12. http://dx.doi.org/10.1002/hon.2900060103
[6]	Cheson, B.D., Bennett, J.M., Grever, M., et al. (1996) National Cancer Institute-Sponsored Working Group Guidelines for Chronic Lymphocytic Leukemia: Revised Guidelines for the Diagnosis and Treatment. Blood, 87, 4990-4997.
[7]	Shanafelt, T.D., Lee, Y.K., Call, T.G., et al. (2006) Clinical Effects of Oral Green Tea Extracts in Four Patients with Low Grade B-Cell Malignancies. Leukemia Research, 30, 707-712. http://dx.doi.org/10.1016/j.leukres.2005.10.020
[8]	Shanafelt, T.D., Call, T.G., Zent, C.S., et al. (2009) Phase I Trial of Daily Oral Polyphenon E in Patients with Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia. Journal of Clinical Oncology, 27, 3808-3814. http://dx.doi.org/10.1200/JCO.2008.21.1284
[9]	Shanafelt, T.D., Call, T.G., Zent, C.S., et al. (2013) Phase II Trial of Daily oral Polyphenon E in Patients with Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia. Cancer, 119, 363-370. http://dx.doi.org/10.1002/cncr.27719
[10]	Ghosh, A.K., Kay, N.E., Secreto, C.R. and Shanafelt, T.D. (2009) Curcumin Inhibits Prosurvival Pathways in Chronic Lymphocytic Leukemia B Cells and May Overcome Their Stromal Protection in Combination with EGCG. Clinical Cancer Research, 15, 1250-1258. http://dx.doi.org/10.1158/1078-0432.CCR-08-1511
[11]	Angelo, L.S. and Kurzrock, R. (2009) Turmeric and Green Tea: A Recipe for B-Chronic Lymphocytic Leukemia. Clinical Cancer Research, 15, 1123-1125. http://dx.doi.org/10.1158/1078-0432.CCR-08-2791
[12]	Mazzolani, F. (2012) Pilot Study of Oral Administration of a Curcumin-Phospholipid Formulation for Treatment of Central Serous Chorioretinopathy. Clinical Opthalmology, 6, 801-806.
[13]	Cuomo, J., Appendino, G., Dern, A.S., et al. (2011) Comparative Absorption of a Standardized Curcuminoid Mixture and Its Lecithin Formulation. Journal of Natural Products, 74, 664-669. http://dx.doi.org/10.1021/np1007262
[14]	Golombick, T. and Diamond, T. (2008) The Potential Role of Curcumin (Diferuloylmethane) in Plasma Cell Dyscrasias/Paraproteinemia. Biologics: Targets and Therapy, 2, 161-163. http://dx.doi.org/10.2147/BTT.S2514
[15]	Golombick, T., Diamond, T., Badmaev, V., et al. (2009) The Potential Role of Curcumin in Patients with Monoclonal Gammopathy of Undefined Significance—Its Effect on Paraproteinemia and the Urinary N-Telopeptide of Type 1 Collagen Bone Turnover Marker. Clinical Cancer Research, 15, 5917-5922. http://dx.doi.org/10.1158/1078-0432.CCR-08-2217
[16]	Golombick, T., Diamond, T., Manoharan, A. and Ramakrishna, R. (2012) Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM) and Curcumin: A Randomised, Double-Blind Placebo-Controlled Cross-Over 4g Study and an Open-Label 8g Extension Study. American Journal of Hematology, 87, 455-460. http://dx.doi.org/10.1002/ajh.23159
[17]	Golombick, T., Diamond, T., Manoharan, A. and Ramakrishna, R. (2013) Long Term Use of Curcumin in Two Smoldering Multiple Myeloma Patients. Journal of Hematological Malignancies, 3, 18-23. http://dx.doi.org/10.5430/jhm.v3n1p18
[18]	Varalakshmi, A.C., Mubarak, A., Pardhasaradhi, B.V.V., et al. (2008) Immunomodulatory Effects of Curcumin: In-Vivo. International Immunopharmacology, 8, 688-700. http://dx.doi.org/10.1016/j.intimp.2008.01.008
[19]	Aggarwal, B.B., Kumar, A., Aggarwal, M.S. and Shisodia, S. (2005) Curcumin Derived from Turmeric (Curcuma longa): A Spice for All Seasons. In: Bagchi, D. and Preuss, H.G., Eds., Phytopharmaceuticals in Cancer Chemoprevention, CRC Press, Boca Raton, 349-387.
[20]	Chang, Y.F., Chuang, H.Y., Hsu, C.H., et al. (2011) Immunomodulation of Curcumin on Adoptive Therapy with T Cell Functional Imaging in Mice. Cancer Prevention Research, 5, 444-452. http://dx.doi.org/10.1158/1940-6207.CAPR-11-0308
[21]	Bhattacharyya, S., Hossain, D.M.S., Mohanty, S., et al. (2010) Curcumin Reverses T Cell-Mediated Adaptive Immune Dysfunctions in Tumor-Bearing Hosts. Cellular & Molecular Immunology, 7, 306-315. http://dx.doi.org/10.1038/cmi.2010.11