Lack of efficacy of 2-chlorodeoxyadenoside in the treatment of splenic lymphoma with villous lymphocytes.

Splenic lymphoma with villous lymphocytes (SLVL) is a B-cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil (CLB) are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second line therapy remains questionable. Although 2-Cda has been evaluated in patients with chronic lymphoid leukemia (CLL) and hairy cell leukemia (HCL), it has been reported as the treatment of SLVL in only one case report. Therefore, we have evaluated its efficacy and toxicity in 7 SLVL patients. The median duration between diagnosis and treatment was 18 months (range, 1 to 59). The patients received 2-CdA (0.1 mg/kg/d) by venous infusion for 7 days with a median number of 1 cycle (range, 1 to 2) either as a first line therapy (one patient) or after a failure of other therapies (splenectomy, chemotherapy). Two patients achieved a complete response. The first one maintained his CR during a follow-up of 9 months and then relapsed; the second patient remained in CR after a follow-up of 20 months. Four patients achieved a partial response and relapsed after a median follow-up of 3.5 months (range, 1 to 4). One patient had no response. The treatment was not well tolerated with many infectious events. In the limits of our study, 2-Cda does not appear to be efficient therapy for SLVL and is not well tolerated for patients in relapse after splenectomy or resistant to CLB.

Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine.

Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a significant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5-7 mg/m(2)/day for 5 days, repeated every 21-28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3-25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study.