Journal of Hematology - Supplements - Haematologica

haematologica 2000; 85(supplement to n. 11):9-11
original paper
Indications and role of allogeneic bone marrow transplantation in
childhood very high risk acute lymphoblastic leukemia
in first complete remission
CORNELIO UDERZO
BMT Unit, Pediatric Hematologic Department, S.Gerardo Hospital, Monza, University of Milano Bicocca, Italy
ABSTRACT
Background and Objectives. Acute lymphoblastic
leukemia (ALL) accounts for approximately one third
of all cancers in children and its outcome depends
on risk factors at the time of diagnosis. While uniform
chemotherapy adopted in multicenter studies
provided a constant improvement in cure rates for
standard risk patients, the results reached in very
high risk patients have been disappointing. The
objective of this review is to point out the role of allogeneic
bone marrow transplantation (alloBMT) in
very high risk childhood ALL on the basis of results
from the current clinical trials.
Evidence and information source. Data covered by
Medline and produced by the authors involved in
ongoing international studies cover a vast “scenario”
of children with very high risk ALL who underwent
allogeneic BMT.
State of art. The author outlines the crucial point of
very high risk factors in childhood ALL in order to
identify those children who are at risk of early
relapse. The main reasons for pursuing alloBMT in
this particular category of patients concern poor
prognostic factors such as molecular biology markers,
structural chromosomal abnormalities and biological
factors (poor prednisone response) including
resistance to initial induction chemotherapy.
AlloBMT in childhood ALL in first complete remission
seemed to lead to a promising disease-free survival
in this patient population when compared with
chemotherapy. The principal biases of the retrospective
studies were the variable very high risk eligibility
criteria, the different first-line therapies
adopted before alloBMT and above all the waiting
time to transplant which could have accounted for
some advantage to alloBMT patients versus chemotherapy
patients.
Perspectives. The author touches upon the preliminary
results of an ongoing international prospective
study as an example of reaching a consensus in the
controversial treatment of childhood very high risk
Correspondence: Cornelio Uderzo, Centro TMO, Clinica Pediatrica, Ospedale
S.Gerardo di Monza,Università di Milano Bicocca, via Donizetti 106,
20052 Monza (MI), Italy. Phone and Fax: international +39-039-2332442
– E-Mail: ctmomonza@libero.it
ALL. This attempt should provide more information
regarding the role of alloBMT in this setting and
should cover an area of particular interest.
©2000, Ferrata Storti Foundation
Key words: ABMT, acute lymphoblastic leukemia
In the last decade many data have emerged
from single institute or multicenter trials
involving children affected by very high risk
ALL in 1 st complete remission (CR), but variable
results have been shown regarding the eventfree
survival (EFS) which ranges from 50% to
70% in patients treated with alloBMT 1-6 and
from 10 to 40% in those treated with
chemotherapy. 6-11 These data primarily depend
on the selection of the patients on the basis of
very high risk eligibility criteria, the intensity of
the first-line treatment and subsequently the
quality of the bone marrow remission.
Current definition of very high risk factors in
childhood ALL
One of the crucial points explaining different
results obtained by different strategies is the
definition of the very high risk criteria over the
years. International co-operative groups (POG,
CCG, I-BFM-SG, AIEOP ) are using a similar risk
classification scheme including the following
very high risk criteria in the ongoing trials: a)
genetic features (MLL rearrangements and BCR
ABL fusion which affect less than 10 % of children
with ALL), b) hyperleukocytosis (white
blood cell count ≥ 100,000/mm 3 ) and/or T-
immunophenotype combined with poor prednisone
response, c) induction failure and, more
recently, d) minimal residual disease (MRD)
persistence. Other previous risk factors such as
myeloid markers, poor prednisone response per
se, hyperleukocytosis or T-immunophenotype
alone, are no longer considered poor prognosis
indicators. 11-15
haematologica vol. 85(supplement to n. 11):November 2000