TREATMENT RELATED DEATHS DURING INDUCTION AND IN FIRST REMISSION IN ACUTE LYMPHOBLASTIC-LEUKEMIA - MRC UKALL-X

The benefits of achieving a long term event free survival of 60-70% by using increasingly intense treatment regimens must be weighed against the increased risk of treatment toxicity. From 1985 to 1990, 1612 chi ldren with childhood acute lymphoblastic leukaemia (ALL) in the UK wer e treated on MRC UKALL X with intensive induction therapy, central ner vous system directed therapy (cranial irradiation and intrathecal meth otrexate), and continuing treatment for two years. There was a randomi sation to receive blocks of additional intensification treatment at fi ve weeks, 20 weeks, not at all, or both. The five year disease free su rvival was 71% for children randomised to two blocks of intensificatio n, a 14% improvement on children randomised to no intensification trea tment. Treatment related mortality in this national multicentre study has been analysed for induction and first remission (including those a fter intensification treatment). There were 38 induction deaths, 2.3% and 53 deaths in first remission, 3.3% (including those from a second malignancy). Thirty one (84%) of the induction deaths followed an infe ction: bacterial in 22 and fungal in nine. Thirty seven infective remi ssion deaths occurred: bacterial in 11, viral in 16, fungal in seven, and three caused by Pneumocystis carinii pneumonia. Ten of these death s followed a block of intensification treatment. The majority of nonin fective remission deaths followed the development of a second tumour. Risk analysis for an induction death showed girls and children with Do wn's syndrome to be at greater risk. For deaths in first remission ana lysis showed an increased risk for bone marrow transplant (BMT) patien ts and children with Down's syndrome. There was no effect of age and l eucocyte count for either group. Most significantly when BMT patients were excluded from the analysis, intensification treatment did not inc rease the risk of remission death.