H e m a t o lo g y E d u c a t io n - European Hematology Association

ently results in a less than 5% cumulative incidence of
CNS relapse at 5 years (from 0.8% to 5%). 14
How to treat initial CNS involvement or CNS
relapse?
1. CNS3 pts
This problem has been evoked in the previous section
(see also “Table 5”). The importance of the systemic
treatment for these patients must be emphasized again,
particularly in protocols trying to omit irradiation. As an
example, the CNS 3 pts, treated without CNS irradiation
in the EORTC 58881, received either 9 or 10 courses
of HD MTX (5 g/m 2 ), depending on their other riskcriteria.
21 Their prognosis in that trial conducted in the
beginning of the 1990s did not differ from the one of the
CNS1 pts (8 year EFS 68.3 % versus 69.7%). 21 Also, in
the DCOG ALL-9 study, considering CNS3 as a highrisk
criterion per se, a 5-year EFS of 67% was observed,
with an overall survival of 80%. 33 These results compare
favorably to those of the BFM-95 (5-year EFS: 50%),
obtained with the use of a 18gy cranial irradiation after
4 courses of HD-MTX (5 g/m 2 ). 5
2. CNS relapse
As CNS relapses are rare and first line treatments are
evolving, no gold standard exists. A recent study from
the UKALL MRC group, reviewing the outcome of
5,564 children with ALL, treated from 1985 to 2001,
has shown a marked trend towards a decrease in combined
relapses, with a progressive shift towards later
relapses (≥ 30 months). 59 Although isolated relapses
declined, the proportional incidence and timing of
relapses remained unchanged. CNS relapses in the UK
MRC studies thus represent 18% of all relapses and are
very early relapses (i.e. CR1 < 18 months) in roughly
37% of the cases. 59
The main points to be considered when tailoring the
treatment of a child with CNS relapseare the length of
first remission (less than 18 months or not), the
immunophenotype (T-cell ALL versus BCP-ALL), the
characteristics of the CNS relapse (isolated or combined),
the presence of minimal disease in the marrow, and a history
of previous CNS irradiation. An additional prognostic
factor found in B-lineage ALL is the NCI classification,
with standard-risk NCI patients having the best prognosis
after an isolated CNS relapse (even if there is some
correlation between length of CR1 and NCI risk). 58,59
Due to this heterogeneity, to small numbers and
sometimes to a long recruitment period, it is not surprising
to find variable outcomes across the studies
(Table 6). 58-63
Some common principles can nevertheless be
accepted:
– To delay cranial or cranio-spinal irradiation for 6 to 12
months allows initial intensification of systemic
chemotherapy. This has led to second EFS rates of
70% to 80% in children with isolated CNS
relapse. 58,61,62
– To reduce as much as possible the dose of irradiation,
investigators of the Children’s Oncology Group have
proposed that patients with an initial remission duration
of