Originally published as JCO Early Release 10.1200/JCO.2006.09.3260 on May 7 2007

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Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Silvia Montoto, Andrew John Davies, Janet Matthews, Maria Calaminici, Andrew J. Norton, John Amess, Sarah Vinnicombe, Rachel Waters, Ama Z.S. Rohatiner, T. Andrew Lister

From the Cancer Research UK Medical Oncology Unit, Barts and the London, Queen Mary's School of Medicine and Dentistry; Departments of Cellular Pathology, Haematology, and Radiology, Barts and the London NHS Trust, London; and the Cancer Research UK Medical Statistics Group, University of Oxford, Oxford, United Kingdom

Address reprint requests to Silvia Montoto, MD, Institute of Cancer, Centre for Medical Oncology, St Bartholomew's Hospital, 45 Little Britain, London EC1A 7BE, United Kingdom; e-mail: silvia.montoto{at}cancer.org.uk

Purpose: To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL).

Patients and Methods: From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%.

Results: The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed.

Conclusion: Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.

published online ahead of print at www.jco.org on May 7, 2007.

Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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