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Cunha KC, Oliveira MC, Gomes AC, Castro LP, Viana MB
Rev Bras Hematol Hemoter. 2012;34(5):361-6
Discussion
In Brazil, despite well-established nationwide collaborative
studies for the treatment of acute leukemia and several solid
tumors, the majority of children who have B-NHL are treated
according to local experience and single-institution protocols. This
retrospective cohort study reports the results of a single service in
the State of Minas Gerais, Brazil. Most of the characteristics of BL
that presented in the children studied here were similar to those
reported for the sporadic forms of BL. The mean age at diagnosis
of our cohort was 4.7 years, similar to that reported for the US and
Europe, which ranged from 5 to 9 years
(9,15)
. As also reported in
previous studies, there was a clear predominance of males. This
fact may raise the question of whether a tumor-suppressor gene for
BL might be located on the X chromosome
(15,16)
.
The main clinical presentation reported among patients with
sporadic BL is the presence of abdominal tumors
(15)
. In the present
study, this was also the most frequent clinical manifestation.
The predominance of intra-abdominal sites, mainly in the right
ileocecal region, was similar to another Brazilian study (75%)
(17)
. In areas of endemic BL, jaw tumor is more common and
may affect as many as 60% of children with one third of them
having involvement of the CNS at diagnosis. Outside endemic
areas, the frequency of jaw involvement is around 15% and CNS
involvement is uncommon, except if there is concomitant HIV
infection
(5,18)
. In our study only one patient had CNS-positive
disease at diagnosis; no inherited or acquired immune deficiencies
were present and this patient remains in first clinical remission.
Because of high tumor growth fraction, in general, patients
show up with advanced disease. So, approximately 70% to 90%
of patients present widespread disease at diagnosis
(4,18,19)
, as
observed in this series.
Many studies have contributed to the identification of possible
risk factors for a bad prognosis, such as age, gender, response
to treatment, CNS or marrow involvement, and chromosomal
abnormalities, such as del(13q) and +7q
(20,21)
. Bulky disease, estimated
through staging systems, resection status and serum LDH levels,
seems to be an important adverse prognostic factor
(15,16,19,22)
. Thus, it
has been shown that a high LDH concentration has a negative impact
on prognosis
(15,22)
. Among our patients, LDH was not a statistically
significant factor, but LDH values were registered in only half of the
patients’ records. It has also been considered that a staging system that
incorporates the situation of tumor resection and LDH levels seems to
be a better indicator of prognosis than disease stage alone
(22)
.
Another way of estimating bulky disease, although
uncommonly used, is based on uric acid concentration at
diagnosis. Advanced clinical stage, the presence of antibodies to
EBV early antigen (anti-EA) and high concentrations of uric acid
and LDH were associated with a significantly poorer outcome in
African children with BL. The authors concluded that the tumor
burden, evaluated by the high concentrations of uric acid and
LDH, was the most important prognostic factor in BL
(23)
.
In a study of Buyukpamukçu et al. high levels of creatinine
and urea had a significant negative impact on the survival of 104
children with NHL, 59 of whom were NHL-B
(24)
. However, our
findings did not corroborate these results. On the other hand, a
high concentration of uric acid at diagnosis was a strong predictor
of adverse outcome in our patients. Therefore, tumor lysis
syndrome also occurs prior to starting chemotherapy and uric
acid can be another good marker of tumor burden.
In this study, 12 patients (26.7%) died, a very similar
situation to that reported for African children (23.8%)
(25)
.
However, this rate is much higher than that recorded in developed
countries, which is around 2.8%
(15)
. The higher mortality rate for
patients treated in low-income countries may be due to a lack of
supportive care required by the chemotherapy scheme employed.
Another problem is malnutrition. These children are probably
at increased risk for therapy-related toxicity, including life-
threatening infections
(26)
. In the present cohort of patients, one
third had malnutrition at admission, a rate similar to that reported
among African children with BL (38.6%)
(25)
.
In most treatment regimens currently used for childhood
and adolescent B-NHL the key component is HD-MTX in both
developed
(8,9)
and developing countries
(27)
. However, dose and
administration schedules vary considerably. Some low-income
countries such as Brazil, Argentina, Lebanon and Iraq have
reported improved survival rates of children with B-NHL,
although the MTX dose did not exceed 2 g/m
2(17,18,28)
. The present
study demonstrates that it is possible to obtain satisfactory results
Table 2 - Factors associated with death of children with Burkitt’s
lymphoma
Variable
Dead Surviving p-value (log-rank)
Gender
Male
9
24
0.99
Female
3
9
Age at diagnosis (months)
< 48
3
10
0.90
≥ 48
9
23
LDH (IU/L)*
< 500
0
7
0.22
≥ 500
3
12
Uric Acid (mg/dL)**
< 7
3
25
< 0.001
≥ 7
9
5
Potassium (mEq/L)†
< 4.2
3
15
0.96
≥ 4.2
3
14
Serum creatinine (mg/dL)#
< 0.8
8
25
0.34
≥ 0.8
4
7
Weight-age Z-score
< -1.28
3
12
0.50
≥ -1.28
9
21
Height-age Z score)
< -1.28
1
7
0.50
≥ -1.28
7
25
Clinical stage††
I-II
1
12
0.50
III-IV
10
21
*Available for only 22 patients at diagnosis
**Available for 42 patients at diagnosis
† Available for 29 patients at diagnosis
†† Available for 44 patients at diagnosis - one patient died before staging
# Available for 40 patients at diagnosis