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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2412-2418
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Bone marrow transplantation versus chemotherapy in the treatment
of very high-risk childhood acute lymphoblastic leukemia in first
remission: results from Medical Research Council UKALL X
and XI
Kate A. Wheeler,
Susan M. Richards,
Clifford C. Bailey,
Brenda Gibson,
Ian M. Hann,
Frank G. H. Hill, and
Judith M. Chessells for the Medical Research Council Working Party on Childhood
Leukaemia
From the John Radcliffe Hospital, Headington,
Oxford, England; the ICRF (Imperial Cancer Research Fund)/MRC Clinical
Trial Service Unit, Radcliffe Infirmary, Oxford, England; the Research
School of Medicine, Leeds, England; the Royal Hospital for Sick
Children, Yorkhill, Glasgow, Scotland; the Great Ormond Street
Hospital, London, England; the Birmingham Children's Hospital,
Birmingham, England; and the Institute of Child Health, London,
England.
The role of bone marrow transplantation (BMT) in first remission of
children with high-risk acute lymphoblastic leukemia (ALL) remains
unclear. There were 3676 patients (aged 1 to 15 years) entered into the
United Kingdom (UK) Medical Research Council (MRC) trials UKALL
X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were
classified as very high (VH) risk and were eligible for a
transplantation from a matched histocompatible sibling donor (MSD). We
tissue-typed 286 patients; 99 patients had a matched related donor, and
76 patients received transplantations. Additionally, 25 children
received transplantations from a matched unrelated donor (MUD) despite
trial guidelines for MSD transplantations only. The median time to
transplantation was 5 months (range, 2 to 19 months), and the median
follow-up was 8 years. The 10-year event-free survival (EFS)
adjusted for the time to transplantation, diagnostic white blood
cell (WBC) count, Ph chromosome status, and ploidy was 6.0%
higher (95% confidence interval (CI),  10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD)
than for the 351 patients treated with chemotherapy (transplantation,
45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer
relapses (31%) compared to relapses in the chemotherapy group (55%);
however, the transplantation group had more remission deaths
(18%) compared to remission deaths in the chemotherapy group
(3%). In contrast the adjusted 10-year EFS was 10.7% higher (95% CI, 2.6% to 24.0%) for patients without a human
leukocyte antigen (HLA)-matched donor than for those
patients with a donor (no donor, 50.4%, vs donor, 39.7%).
In conclusion, for the majority of children with VH-risk ALL, the
first-remission transplantation has not improved EFS.
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