Journal of Hematology - Supplements - Haematologica

68
ogous stem cells causing recurrence of disease,
the importance of sensitive and specific assays
(e.g. immunocytology and reverse transcriptionpolymerase
chain reactions) and the role of various
methods of selection will be discussed briefly
in the chapter dedicated to general aspects.
There are some reports about stem cell rescue
with selected CD34 + cells. 12,13 In 1997, Handgretinger
et al. published their results about the
treatment of 20 children with NB, 15 of whom
had received positively selected CD34 + peripheral
progenitor cells. A mean log depletion of
tumor cells of 1.41 was obtained with prompt
(median 12 days, range 10-16 ANC) neutrophil
recovery (greater than 0.5×10 9 /L) and prolonged
platelet recovery (median 30 days, range
16-150 to transfusional independence). No data
about long-term side-effects or EFS are reported.
Kanold et al. 13 reported a series of 23
patients in whom successful neutrophil reconstitution
but delayed platelet recovery (59 days,
range 22-259 to more than 50×10 9 /L) was seen.
Major concerns are the persistently low in CD4 +
lymphocyte levels and the high incidence of serious
late infections, especially the occurrence of
2 EBV-lymphoproliferative diseases.
Ewing’s sarcoma
Metastatic disease at diagnosis, associated
with large tumor size and pelvic site are the most
significant adverse prognostic factors for
patients suffering from Ewing’s sarcoma; in this
group the EFS at two years is < 30%. 14
Two analyses based on the EBMT experience
were conducted. The first on 210 patients not in
CR at the time of HSCT, the majority of whom
had previous progressive disease, showed an
overall response rate of 53% (CR obtained in
27%). 15 In the second trial, performed in 63 children
in first or second CR, the DFS at five years
was 21% and 32%, respectively, the non-TBI regimens
being slightly more successful than the
TBI-containing regimens, and the association of
busulfan, melphalan seeming to produce the
best DFS (51%). 16
Remarkable results (DFS at 6 years,45%) were
obtained by the CESS group in a small population
of 17 patients using the association TBI,
melphalan, etoposide ± carboplatin. 17 The same
group suggested the usefulness of IL-2 immunotherapy
after transplantation; the difference
in DFS in children receiving or not receiving IL-2
is significant (52% versus 22%, p < 0.05). 18
The challenge in the future will be a better definition
of groups of patients, up to now all listed
togheter as poor risk patients (for example
those with marrow spread, multiple bone localizations,
recurrent or resistant disease, excluding
probably children with a single lung metastasis
or late and isolated relapse) in which HSCT can
be really advantageous. The immunologic characteristics
of Ewing’s tumor and the consequent
possibility of targeted immunotherapy are fields
to be explored.
Rhabdomyosarcoma
In the last ten years the reasons for performing
HSCT in children with rhabdomyosarcoma
(RMS) were the presence of metastasis and
relapse after a primary response. Since 1989 the
European Intergroup Study has designed two consecutive
protocols for the treatment of patients
with metastatic disease at diagnosis. The first
study was based on a six-drug regimen without
HSCT, while the second trial was carried out
with HSCT in children in clinical CR after the
second cycle of chemotherapy The results can
be summarized as follows: 19 a) the achievement
of CR after the second cycle is crucial with
respect to the 3-year EFS for both groups (27.8%
versus 10.8%, p= 0.0001); and b) the 3-year EFS
rates were 29.7% for HSCT group and 19.2% for
non HSCT group (p= 0.3).
The conclusions of this study as those of
Koscielniak et al., 20 are not in favor of routine
use of HSCT in RMS and emphasize the need of
controlled clinical trials.
Medulloblastoma and infants with brain tumors
The prognosis of a consistent number of children
with newly diagnosed malignant brain
tumors, especially for those with some unfavorable
histologic subtypes, in the absence of radical
surgical resection and with metastatic presentation
remains poor despite surgery, irradiation
and conventional chemotherapy. Similarly
patients whose tumor recurs despite initial therapy
continue to experience a dismal outlook
with these conventional strategies of treatment.
In an attempt to improve the outlook, strategies
utilizing high-dose chemotherapy with autologous
stem cell rescue have been developed.
These studies, conducted initially in patients
with recurrent tumors, were then extended to
very young children with various malignant brain
tumors at diagnosis in an attempt to avoid irradiation
to the brain. 21
In several reports 22-24 patients with recurrent
medulloblastoma, for which long-term survivors
are rarely described, have benefited from HSCT.
In the report of the Duke University experience
concerning 49 patients with recurrent brain
tumors 23 an important message is that 4/6 cases
with local recurrence are disease-free survivors,
while none of the 12 with metastatic
relapse were event-free survivors. In the Sloan-
Kettering study 24 the EFS at 3 years of 23
patients treated with the association carbo-
haematologica vol. 85(supplement to n. 11):November 2000