Large‐cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine–rituximab‐containing regimens: natural history‐ or therapy‐related complication?

Abstract

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This

Hodgkin's Type of Richter's Syndrome in Familial Chronic Lymphocytic Leukemia Treated with Cladribine and Cyclophosphamide

“…VH, variable region gene, N, randomly inserted; DH, diversity region; JH, joining region gene. during or shortly after the initiation of regimens containing FA and rituximab before transformation occurred [37]. There were also cases of H-RS developing after treatment with FA [3,20,21].…”

Plasmablastic transformation of low-grade CD5+ B-cell lymphoproliferative disorder with MYC gene rearrangements

“…It has been proposed that prolonged immunosuppression in CLL patients may increase the risk of developing RS due to humoral and cellular dysfunctions [20]. Therapies with purine analogues, including fludarabine and cladribine, have been documented to be associated with RS [21][22][23][24][25]. EBV has been observed in a substantial number of high-grade lymphoma in RS, indicating that it may also contribute in the transformation [25][26][27].…”

Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS)

“…Perhaps instead, certain nonanthracycline regimens may be associated with an increased risk of transformation as has been hypothesized with purine analogs. 24,25 Fludarabine constituted a small portion of the anthracycline-and nonanthracycline-containing regimens in our study, so analysis of this potential scenario was not feasible. In sum, treatment strategies cannot be recommended from this observational data, and the potential role for maintenance rituximab in reducing transformation will require careful attention to final reporting of HT rates in maturing randomized trials of maintenance rituximab.…”