Originally published as JCO Early Release 10.1200/JCO.2007.15.1530 on December 8 2008

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Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside Analogs

Xavier Leleu, Jacob Soumerai, Aldo Roccaro, Evdoxia Hatjiharissi, Zachary R. Hunter, Robert Manning, Bryan T. Ciccarelli, Antonio Sacco, Leukothea Ioakimidis, Sophia Adamia, Anne-Sophie Moreau, Christopher J. Patterson, Irene M. Ghobrial, Steven P. Treon

From the Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA; and Service des maladies du sang, Hopital Claude Huriez, Centre Hospitalier Regional Universitaire, Lille, France

Corresponding author: Steven P. Treon, MD, PhD, Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, 44 Binney St, Mayer 548A, Boston, MA 02115; e-mail: steven_treon{at}dfci.harvard.edu

Purpose Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM.

Patients and Methods We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years.

Results Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months.

Conclusion These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.

published online ahead of print at www.jco.org on December 8, 2008

Supported by a grant from the Franco-American Fulbright Foundation (X.L.).

X.L. and J.S. contributed equally to this work.

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

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