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Treatment of High Risk Leukaemia - Results of MRC Childhood Acute Lymphoblastic Leukaemia Study MRC HR-1

Treatment of High Risk Leukaemia - Results of MRC Childhood Acute Lymphoblastic Leukaemia Study MRC HR-1

Blood 100(11): Abstract No 3019, November 16

Between April 1997 and December 1999 151 children deemed to be at ultra high risk (60% on previous protocol) of relapse of ALL were treated on a non-randomised single arm treatment regimen. This group represents 15% of a total of 994 patients with ALL presenting during the same time interval. Risk was determined either by using the Oxford hazard Score, (Cox regression analysis of age, sex and white cell count at presentation) in 123 or by unfavourable cytogenetics in 28 (Ph+ve = 13, MLL gene rearrangement = 11, near haploidy = 4). 126 (83%) were male, 95 (63%) were over 10 years of age and 72 (48%) had a presenting WCC > 100 x 109/l. Immunophenotypes were; T cell 62 (41%), precursor-B cell 80 (53%) and other 8 (5%). Patients received three drug induction (Vinc, Pred, Asparaginase plus it MTX) followed by early intensification at week 5 (Dauno, Etoposide, Cytosine, Pred, Vinc and Thioguanine), an intermediate intensification at week 8 (Vinc, Dexa, Asparaginase then Cyclo, Cytosine and Thioguanine over an 8 week period) and a late intensification (same as early) at week 20 followed by CNS directed therapy and cyclical intensive maintenance treatment for a total of 8 cycles stopping at 2 years. Choice to search for a bone marrow transplant (BMT) donor and proceed to BMT was a physician decision. There were 7 deaths in the first 60 days of therapy, one death from resistant disease at 277 days from diagnosis and 5 deaths in remission. 95% patients achieved remission including 11 patients (7%) remitting beyond 60 days (median time to remission 74 days, range 61-414). There have been 50 relapses (4 year rate = 41%). 30 (20%) patients had a BMT in first remission (related donor=21, unrelated=9) of whom 22 are alive, and 17 post relapse (related=5, unrelated=10, autograft=2) with 7 alive. EFS is 54% at 4 years from diagnosis (compared with 81% for the non-high risk patients (2p<0.00001). Patients treated on this single arm regimen were high risk by hazard score or cytogenetics at diagnosis, no account was taken of the speed of response to therapy in order to assign risk (compared with NCI high risk which includes slow early response to therapy). Given the high risk of the patients treated on this regimen the EFS is good. Comparison within 86 for whom a sibling donor was sought, those with versus those without a match, shows no difference in EFS, and the role of BMT has not been established in this group of patients.

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Accession: 035980496

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