[Treatment with fludarabine of chronic refractory lymphoid leukemia].

PURPOSE

New antimetabolic drugs, purine-analogous, have been introduced in the treatment of advanced or refractory cases of chronic lymphocytic leukaemia (CLL), fludarabine (FLU) being one of such drugs. The results attained with FLU in 6 cases of refractory CLL are reported.

PATIENTS AND METHODS

The efficacy and toxicity of FLU was evaluated in 6 patients (median age 63 years) between March 1993 and March 1994. Five patients were in stage III-IV and one in stage II of the Rai's system, and they were refractory to the usual treatment. The dosis used here was 30 mg/sq m/day, for 5 days every 4 weeks, up to a total of 6 therapeutic courses. The response was assessed after 3 and 6 courses. Anti-infectious prophylaxis was made with co-trimoxazole, monthly benzathine penicillin G and isoniazid in Mantoux-positive patients. The response criteria were those given by the NIC Working Group for CLL.

RESULTS

The patients received 2 to 6 courses. None of them attained complete remission: 1 had nodular remission, 2 had partial remission, 2 responded partially although not reaching criteria for partial remission (1 died of pancytopenia), and 1 had disease progression and died after the second course. Fast and important reduction of the lymphocyte count as well as the CD4 lymphocytes was present in all cases. Bone-marrow infiltration decreased strikingly in 2 cases and the platelet count improved in 3 cases and worsened in 2 others. The following toxicity was recorded: 2 patients had nausea, 5 had neutropenia (below 500 x 10(9)/L in 3 instances) and 4 had thrombocytopenia (lower than 40 x 10(9)/L in one case). In 26 therapeutic courses there were 10 febrile episodes (1 for pneumonia, 1 for gastroenteritis and 8 without any septic foci); 1 patient developed pulmonary tuberculosis after completing the treatment and one patient died of posttransfusion graft versus host disease after splenectomy once she had completes six courses.

CONCLUSION

This experience confirms the efficacy of FLU in the treatment of refractory B-CLL patients and is in agreement with previous reports as no response is initiated after the 3rd course. The lymphocyte count decreases quickly and strikingly. Depletion of CD4 lymphocytes along with neutropenia and hypogammaglobulinaemia make these patients highly sensitive to all types of infection, chiefly by opportunistic germs, so adequate anti-infectious prophylaxis is of great importance. The two patients with pre-treatment haemoglobin and platelet values lower than 10 g/dL and 40 x 10(9)/L, respectively, were the only ones in need of transfusion. No cumulative myelosuppression was appreciated.