Journal of Hematology - Supplements - Haematologica

4
sources of hematopoietic stem cells include
unrelated donors and autologous marrow. The
results of BMT from unrelated donors demonstrate
a 35% of DFS at 8 years. The search for an
unrelated donor can be very long, so, when a
related donor is not available, allogeneic BMT
should be considered just as if chromosome
alterations are present or in patients who do not
respond to chemotherapy. Otherwise, transplants
involving unrelated donors for AML in
remission should proceed largely in the context
of a clinical research protocol. 13 As far as regards
autologous BMT, studies by both the Children
Cancer Group and the Pediatric Oncology
Group have not shown any difference in DFS
between children receiving autologous transplant
and those receiving continued chemotherapy
(50% and 44%, respectively for the CCG
study; 38% and 36% for the POG study). 12,13
Allogeneic bone marrow transplantation
in chronic myelogenous leukemia
Allogeneic or syngenic BMT is an effective
treatment for chronic myelogenous leukemia
(CML); 17 the results are dependent on the phase
of the disease at the time of BMT. Allogeneic
grafting should ideally be performed during the
chronic phase within 1 year from diagnosis, but
patients in advanced phases may also be treated
with this procedure on an individual basis.
Children who receive a transplant during blast
crisis have a 10% to 20% DFS, those in accelerated
phase have a 35% to 40% DFS, and those
in chronic phase have a 50 to 80% DFS. Among
chronic phase patients the major factor predicting
outcome is the length of time between
diagnosis and transplant: 17-18 those who receive
a transplant within the first year after diagnosis
have a DFS of 80-85% in the first 3 years, whereas
those who receive a transplant more than 2
years after diagnosis have a DFS of 50-60%. 19
Unrelated donor marrow transplants give
results similar to those obtained from suitably
matched family member donors but are usually
performed in the context of clinical research protocols.
Allogeneic bone marrow transplantation
in myelodysplastic syndromes
Myelodysplastic syndromes (MDS) (Table 4)
represent a heterogeneous group of clonal alterations
of hematopoiesis, having in common
cytopenia, dysplasia and a predisposition to
evolve in acute myeloid leukemia (20-30% of
cases). These disorders are typical of adult age:
they represent only 2-9% of childhood hematologic
malignancies; furthermore MDS of childhood
appear to run a more aggressive course,
Table 4. Myelodysplastic syndromes in children.
PRIMARY MYELODYSPLASIA
Refractory anemia (RA)
Refractory anemia with ring sideroblasts (RARS)
Refractory anemia with excess of blasts (RAEB)
Refractory anemia with excess of blasts in transformation (RAEB/T)
Juvenile chronic myeloid leukemia
Congenital myelodysplastic sindrome
SECONDARY MYELODYSPLASIA
Familial
Therapy induced
Table 5. Constitutional abnormalities and somatic
derangements associated with MDS in children.
• Down’s syndrome
• Trisomy chromosome 8
• Monosomy chromosome 7
• Ataxia-teleangectasia
• Bloom’s syndrome
• Xeroderma pigmentosus
• Nijmegen’s syndrome
• Neurofibromatosis I
• Schwachman’s syndrome
especially forms with elevated numbers of blasts
in marrow (primary MDS). 15,20,21 Several conditions
have been identified as predisposing factors
for childhood MDS and are reported in
Table 5.
Refractory anemia, refractory anemia with ring
sideroblasts and refractory anemia with
excess of blasts in transformation
Refractory anemia (RA) is frequent in children
with familial hematologic disorders or constitutional
problems. Refractory anemia with ring
sideroblasts (RARS) is the least common of all
the group: typically it is observed in girls with constitutional
abnormalities and karyotype alterations
(frequently monosomy 7); it can be a
genetic mitochondrial disorder with polyclonal
hematopoiesis that seldom progresses to
leukemia but rather terminates in multiorgan failure;
few cases of spontaneous regressions are
described. Refractory anemia with excess of
blasts (RAEB) and particularly with excess of
blasts in transformation (RAEB/T) can be
observed in older children: these forms are more
aggressive than other myelodysplasias because of
a higher progression rate to AML and poor survival.
Allogeneic BMT performed early in the course
of the disease and from the most closely
matched source available confers the best hope
for long-term survival. Some series record a dis-
haematologica vol. 85(supplement to n. 11):November 2000