HIGH-INCIDENCE OF INFECTIONS AFTER 2-CHLORODEOXYADENOSINE (2-CDA) THERAPY IN PATIENTS WITH MALIGNANT-LYMPHOMAS AND CHRONIC AND ACUTE LEUKEMIAS

Background: 2-chlorodeoxyadenosine (2-CDA) is a new purine analogue wh ich has been shown to be highly active in lymphoproliferative disorder s. In this clinical trial we assessed 2-CDA toxicity and response rate in patients with various haematological malignancies who were heavily pretreated and mostly refractory to standard treatment regimens. Pati ents and methods: Twenty-two refractory patients, 51 relapsing after s tandard chemotherapy and seven non-pretreated patients were treated in a non-randomized prospective phase II multicentric study. Their media n age was 54 years (range 18-84) and 56 of them were male. Thirty-one had non-Hodgkin's lymphoma NHL), 11 chronic lymphocytic leukaemia (CLL ), 1 prolymphocytic leukaemia (PLL), 13 hairy-cell leukaemia (HCL), 2 mycosis fungoides (MF), 3 multiple myeloma, 7 acute myeloblastic leuka emia (AML), 2 acute lymphoblastic leukaemia (ALL), 6 chronic myeloid l eukaemia (CML) in blast crisis, 2 Hodgkin's disease, 1 Waldenstrom's m acroglobulinemia and 1 Langerhans histiocytosis. 2-CDA 0.1 mg/kg/day w as given as a continuous intravenous infusion for 7 days and recycled every 4 weeks. Results: One hundred thirty-two courses of 2-CDA were a dministered to 80 patients, 76 of whom were evaluable for response. A) Toxicity: Myelosuppression: Neutropenia to over 50% of initial value occurred in 46% of patients, thrombocytopenia in 8%, and lymphopenia < 0.5 x 10(9)/l was seen in 41%. Infections occurred in 34/80 patients ( 43%). The risk of severe infections (WHO grades 3-4) correlated with i ncreasing number of years after first diagnosis (p = 0.01) and low lym phocyte counts on days 1 and/or 14 (p = 0.04); 21 infections were oppo rtunistic. B) Response: 70% patients with lymphoproliferative disorder s of low malignancy attained complete or partial response (low-grade N HL 12/16, CLL + PLL 9/12, HCL 13/13, MF 2/2, myeloma 0/3); in patients with AML, ALL, CML in myeloid (n = 4) or lymphoid (n = 2) blast crisi s and high-grade lymphoma responses were seen in only 11%. Response wa s inversely related to the number of pretreatments (p = 0.045). In res ponding NHL patients the mean lymphocyte count on day 14 of cycle I wa s significantly lower (median 0.6 x 10(9)/I) than that of non-responde rs (1.2 x 10(9)/l, p = 0.04). Conclusion: 2-CDA had a high activity ev en in heavily pretreated and refractory patients with low-grade lympho proliferative disorders. In contrast to previously published studies, infections, mainly opportunistic, were a serious side effect in our st udy. In patients with severe lymphopenia at therapy initiation, the va lue of prophylactic anti-infective treatment should be studied.