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Cunha KC, Oliveira MC, Gomes AC, Castro LP, Viana MB
Rev Bras Hematol Hemoter. 2012;34(5):361-6
n = 1), bone marrow involvement (≥ 25% L3-morphology blasts;
n = 2), and an erroneous initial diagnosis (n = 1). In this latter
case, the patient was initially diagnosed as BL on morphological
grounds. After complete immunophenotyping characterization,
the diagnosis was changed to lymphoblastic B-cell lymphoma.
The medical records were reviewed to collect demographic
data (age, gender), clinical data (medical history, physical
examination, nutritional status, clinical presentation), diagnostic
procedures (imaging studies, bone marrow aspiration,
cerebrospinal fluid - CSF analysis), staging, laboratory data
(lactate dehydrogenase - LDH levels, blood counts, serum
electrolytes, liver and kidney profile), treatment, and outcome.
Diagnosis was made by incisional or excisional biopsy, or
cytological examination of pleural or abdominal effusions.
Karyotype studies were not available at the time.
All the diagnoses were confirmed according to the
morphologic and immunohistochemistry criteria defined
by the World Health Organization (WHO) classification
(2)
.
Immunohistochemistry was performed using monoclonal
antibodies CD20, CD10, CD79a, CD30, CD3, CD15, TdT,
CD45, and CD45RO. Confirmation of B-cell lineage by
immunophenotyping required 50% or more neoplastic cells to
express CD45, CD10, CD20, and CD79a. Pleural or abdominal
effusions were examined by flow cytometry.
Clinical staging was based on the St. Jude Children’s
Research Hospital staging system
(10)
. Central nervous system
(CNS) disease was diagnosed by the presence of morphologically
identifiable lymphoma cells (regardless of quantity) in CSF,
an intracerebral mass or cranial nerve palsy not caused by an
extracranial mass. To evaluate malnutrition, Z-scores of weight
for age (WAZ) and height for age (HAZ) were used
(11)
. The chosen
cutoff point to discriminate undernourished from well-nourished
status was a Z-score of less than 1.28 (10th percentile). Although
less specific, it is more sensitive than the cutoff point of Z = -2.
The variables studied for a possible association with
prognosis were gender, age, staging, nutritional status, serum
LDH and kidney function.
Treatment
Patients admitted between 1981 and 1987 were treated
according to the modified LSA2L2protocol of the Memorial Sloan-
Kettering Cancer Center
(12)
. After 1987, the patients were treated
with a BFM-83-based protocol (Berlin-Frankfurt-Münster)
(13)
. The
first cycle of treatment was modified in patients with severe clinical
events at diagnosis, such as a high tumor burden associated with
pleural and peritoneal effusions, tumor lysis syndrome and sepsis.
At diagnosis, all patients were vigorously hydrated and alkalized
with NaHCO
3
associated with allopurinol. Treatment of parasitic
infection was performed before the beginning of chemotherapy.
Response criteria
Complete remission (CR) was defined as the disappearance
of all tumor masses confirmed by clinical examination and
imaging investigations, when necessary one month after therapy.
After the end of treatment, the patients were followed at 30-day
intervals during the first year, at 60-day intervals during the second
year and at 3- to 6-month intervals up to five years. Progression of
the local tumor was defined if the tumor site showed no decrease
in size after the initiation of chemotherapy. Relapse was defined
as the recurrence of lymphoma with the same histological or
immunophenotypic features as the initial one at any site after CR
was achieved.
Local relapse was diagnosed when it involved a
previously involved site (except bone marrow and CSF).
Statistical analysis
The time limit for the current study was the end of March
2008. The overall survival (OS) was defined as the time from
diagnosis to date of death due to any cause or date of last follow-up
contact for patients who were alive. The OS was analyzed using
the Kaplan–Meier method. The analysis of prognostic factors
was based on the OS and the comparison of curves by the log-rank
test
(14)
. Data are reported as medians and interquartile range (IQ)
or means and standard deviation (SD), when appropriate. The
Mann-Whitney or Kruskal-Wallis tests were used to compare
nonparametric continuous variables. Dichotomous variables were
compared by the two-tailed chi-square test or Fisher exact test.
The level of significance was set for a p-value ≤ 0.05. Statistical
analysis was performed using the SPSS software (version 10.0).
EPI INFO 6.0 was used to assess the scores of height for age
(HAZ) and weight for age (WAZ).
Ethical issues
The study was approved by the Research Ethics Committee
of UFMG. Written informed consent was obtained from the
guardians of the patients and, when appropriate, from the patients
themselves, according to the Helsinki Declaration.
Results
Patient characteristics
The median age at diagnosis was 4.7 years (range: 11.5 months
to 13.2 years). There was a predominance of males (2.8:1). Diagnosis
was based on cytological examination of abdominal effusions in
three patients (6.7%), pleural effusions in two patients (4.4%), and
on tumor biopsies for the other cases. Immunohistochemistry was
performed in 29 patients. For one patient immunohistochemistry
was inconclusive because of technical problems with the fixing of
samples. Malnutrition, as defined by WAZ and HAZ, was present
in one third and one fifth of the patients, respectively. The clinical
and demographic characteristics of the patients are shown in Table 1.
Abdominal tumors, occurring in 30 patients (66.7%), were the most
common presenting feature. Abdominal involvement was associated
with disease at other sites, such as pleural and abdominal effusions,
and peripheral lymphadenopathy.Mediastinal involvement and facial
involvement were observed in three patients (6.7%) and six patients
(13.3%), respectively. Of these latter children, jaw tumors were
observed in three patients and tumors located in the nasopharynx
in the other three. Other involved organs included peripheral lymph
nodes (two patients) and CNS (one patient). Three patients had