Intensive consolidation chemotherapy for acute lymphoblastic leukaemia (UKALL X pilot study)

Abstract

Eighty two children with acute lymphoblastic leukaemia presenting at this hospital received one or two modules of intensive chemotherapy to consolidate remission. Modules were given after four and roughly 19 weeks on treatment. Each included two doses of daunorubicin (45 mg/m2/day), cytosine arabinoside (100 mg/m2 twice daily X 5), etoposide (100 mg/m2/day X 5), and 6-thioguanine (80 mg/m2/day X 5). A total of 132 courses were given. This study included all new patients except girls aged 1-14 years with presenting leucocyte count less than 20 X 10(9)/l. Twenty patients with recurrent disease were also included. The first 32 patients were given cytosine as a 24 hour infusion, but combined with the other agents this was associated with severe intestinal toxicity, which necessitated a change to a less toxic 12 hourly bolus regimen. The complications of the module are reviewed in terms of myelosuppression, enterotoxicity, infection, and other clinical problems encountered. All patients became profoundly neutropenic and thrombocytopenic. The latter was significantly more severe after cytosine infusion. Overall, 64% received platelet transfusions and 85% were re-admitted with fevers requiring intravenous antibiotics for between four and 56 days. Gastrointestinal toxicity with the modified module occurred in 38% of patients and was severe in 13%. This intensification module has been adopted by the Medical Research Council Working Party on Childhood Leukaemia for use in a multicentre study (UKALL X) and the details of the problems encountered in the pilot study may be of value to other centres now using this protocol.