To the Editor:
Purine analogues, including cladribine (2-chlorodeoxyadenosine), are increasingly used in the treatment of Waldenstrom's macroglobulinemia and other hematologic cancers. (1) Cladribine can cause profound immunosuppression, lymphopenia, and increased susceptibility to opportunistic infections. (2) We report on a patient with Waldenstrom's macroglobulinemia in whom an Epstein-Barr virus (EBV)-associated diffuse large-cell lymphoma developed after treatment with cladribine.
A 69-year-old woman received the diagnosis of Waldenstrom's macroglobulinemia with IgM kappa in 1991. Because of the progression of the disease, treatment with standard doses of cladribine was initiated in June 1994 and repeated in August 1994. The patient had a remarkable response, with alleviation of her symptoms and more than 90 percent reduction of the serum paraprotein level. Five months after the completion of treatment with cladribine, pain developed in the right hip, and a right acetabular lytic lesion was found.
Laboratory tests showed lymphopenia, normal serum viscosity, and a stable IgM level. Additional studies revealed a mass in the liver. Biopsies from both the right acetabulum and the liver revealed morphologically identical lymphocytic infiltrates that were consistent with the presence of diffuse large-cell lymphoma. The liver-biopsy specimen was positive on staining for CD20, IgA kappa, and EBV latent membrane protein 1 (Figure 1). The patient subsequently died, and an autopsy revealed diffuse large-cell lymphoma that was positive for EBV latent membrane protein 1 in both liver and kidney specimens. An antemortem serologic test was positive for EBV (data not shown).
The demonstration of IgA kappa light chain and the positive staining for EBV latent membrane protein 1 in the lymphoma sample strongly suggest the development of a new, aggressive B-cell diffuse large-cell lymphoma rather than Richter's transformation, which is rare in Waldenstrom's macroglobulinemia. (3) Although the role of prior EBV infection in the development of diffuse large-cell lymphoma remains to be investigated, this case justifies the cautious use of cladribine in patients who are seropositive for EBV.
Ruben Niesvizky, M.D.
Andrew X. Zhu, M.D., Ph.D.
Diane Louie, M.D.
Joseph Michaeli, M.D.
Memorial Sloan-Kettering Cancer Center
New York, NY 10021