Elsevier

Leukemia Research

Volume 30, Issue 6, June 2006, Pages 707-712
Leukemia Research

Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies

https://doi.org/10.1016/j.leukres.2005.10.020Get rights and content

Abstract

Green tea or its constituents have long been touted as a health promoting substance including claims it may have cancer prevention properties. We previously reported the in vitro ability of one tea polyphenol, epigallocatechin gallate (EGCG), to induce apoptotic cell death in the leukemic B-cells from a majority of patients with chronic lymphocytic leukemia (CLL). After the publication of our findings many patients with CLL and other low grade lymphomas began using over-the-counter products containing tea polyphenols despite the absence of evidence to suggest clinical benefit, definition of possible toxicities, or information on optimal dose and schedule. We have become aware of four patients with low grade B-cell malignancies seen in our clinical practice at Mayo Clinic who began, on their own initiative, oral ingestion of EGCG containing products and subsequently appeared to have an objective clinical response. Three of these four patients met criteria for partial response (PR) by standard response criteria. Although spontaneous remission/regression is occasionally observed in individuals with low grade B-cell malignancies, such events are rare. Several patients presented here had documented steady clinical, laboratory, and/or radiographic evidence of progression immediately prior to initiation of over-the-counter green tea products and then developed objective responses shortly after self-initiating this therapy. Such anecdotes highlight the need for clinical trials of tea polyphenols to define the optimal dosing, schedule, toxicities, and clinical efficacy before widespread use can be recommended. An NCI sponsored phase I/II trial of de-caffeinated green tea extracts for patients with asymptomatic, early stage CLL opened at Mayo Clinic in August 2005.

Introduction

Green tea or its constituents have long been touted as a health-promoting substance with claims of cancer prevention properties. Recent studies have more precisely identified the active chemical compounds in green tea that may mediate these effects. These compounds are as a group termed tea polyphenols or catechins [1]. In March 2004, we reported the in vitro ability of one tea polyphenol, epigallocatechin gallate (EGCG), to induce apoptotic cell death in the leukemic B-cells from a majority of patients with chronic lymphocytic leukemia (CLL) [2]. EGCG also reduced levels of the protein Mcl-1, an anti-apoptotic protein of known importance in CLL B-cell resistance to apoptosis [3], [4], at doses as low as 0.68 μM. The serum concentration of EGCG achieved by tea drinkers is between 0.1 μM and 1.0 μM [5], [6], [7]. Our findings suggested EGCG's effect on CLL B-cells was, at least in part, mediated through its affects on the VEGF receptor [2]; however, a multiplicity of other biologic mechanisms for EGCG effects on tumor cells has also been proposed [1], [8], [9].

Most low grade, B-cell malignancies are incurable with current treatments, and asymptomatic patients with these illnesses are often managed with what physicians term “watchful waiting” [10]. After the publication and subsequent dissemination of our findings with EGCG in CLL by the lay press [11], some patients with CLL and other low grade lymphomas began using over-the-counter products reported to contain tea polyphenols despite the absence of evidence on clinical benefit, toxicity, or knowledge of optimal dose and schedule.

Section snippets

Methods

Based on feedback from colleagues and our patients, we become aware of several patients with low grade, B-cell malignancies seen at Mayo Clinic who, of their own initiative, began oral ingestion of EGCG containing products and appeared to objectively derive clinical benefit. With IRB approval, patient charts were subsequently abstracted for the clinical details regarding diagnosis and clinical course prior to and after initiating green tea containing products. Patients were contacted to

Discussion

In total, our report on these patients with low grade B-cell malignancies adds to the growing evidence that food products that contain polyphenols have anti-tumor activity. In fact, the polyphenol containing agents have not only been shown to have anti-tumor activity but have been linked to chemoprevention of human tumors. A number of epidemiologic studies have linked consumption of green tea to a decreased risk of cancer. A wide range of animal models has also supported green tea's ability to

Acknowledgements

This work was supported in part by grant nos. CA95241 and CA95241-S from the National Institutes of Health, National Cancer Institute, and philanthropic endeavors of Mr. E. Spencer. TDS and CSZ received partial salary support NCI Lymphoma SPORE CA97274.

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