Acute Leukemias - Republican Scientific Medical Library

192 Chapter 15 · Burkitt’s Acute Lymphoblastic Leukemia (L 3ALL) in Adults
absence of massive extramedullary tumor mass, especially
in the abdomen, and when the presentation consists
mainly of signs of marrow failure. Marrow infiltration,inL
3ALL, is in fact generally massive, with greater
than 50% blasts. The disease largely predominates in
males (by about 3 to 1), and median age ranges between
25 and 35 years, but about one quarter of the patients are
older than 50. Hepatosplenomegaly and moderately enlarged
lymph nodes are seen in 50–60% of the cases.
The frequency of CNS involvement at diagnosis has
been reported to vary greatly, from 12% to greater than
70%. This variation may have different causes. One of
them could be taking into account clinical findings like
mental neuropathy. Mental neuropathy is indeed a frequent
clinical finding in BL and L3ALL, rarely seen in
other lymphomas or acute leukemias. It appears to result
from infiltration of inferior dental nerves, and
therefore can reasonably be considered as a sign of
CNS disease, even when isolated [8]. We observed it
in 60% of our L 3ALL cases, and only one half of those
patients had other signs of CNS involvement. CNS disease,
in L3ALL, is also often diagnosed in the presence
of other cranial nerve palsies, not always associated to
the presence of blasts in the CSF. Other organs are involved
in about 30% of the L 3ALL cases, including mediastinal
tumors, and stomach, abdomen, skeleton and
epidural masses, leading to paraplegia, which can be a
presenting sign of the disease.
Thrombocytopenia is present in most patients, but
anemia is less frequent; leukocytosis is found in two
thirds of the cases but exceeds 50´10 9 /l in only 10–
20% of the patients. Circulating blasts are often associated
to myelocytes and metamyelocytes, a rather unusual
finding in most other types of acute leukemias.
A high correlation is found, in ALL, between L 3 morphology
and the presence of surface immunoglobulins,
(sIg) although cases of morphologically L 1 or L 2 ALL
with sIg, and cases of morphologically L3ALL without
sIg have been reported, both in children and adults
[9–12]. In the study of Hoelzer, et al., six of the 68 patients
included had discrepancies between morphological
and immunological diagnosis: Five were positive for
sIg but had L 1 or L 2 morphology; one had L 3 morphology
but no sIg. Patients with sIg and L 1 or L 2 morphology
had a very poor outcome, and probably constitute
(both in adults and children) a subtype of ALL different
from L3ALL, that requires other therapeutic approaches.
In the same report, three additional patients with L 3
morphology were found to have a different immuno-
phenotype (c-ALL in two cases and preB-ALL in one
case). Kantarjian et al. also reported L 3 morphology in
only 11 of their 18 cases of mature B cell ALL.
t(8;14) is the most frequent translocation observed
in blasts cells, t(2;8) and t(8;22) being only occasionally
seen. In recent series, 38–68% of L3ALL had typical
t(8;14) or t(2;8) and t(8;22) abnormality detected [9,
13–15]. Comparative genomic hybridization (CGH) analysis
also showed that L 3ALL had higher number of cytogenetic
changes, including a high level of genetic amplification
than BLs [16]. Additional chromosomal abnormalities
are found in 30–40% of the patients when
karyotype is assessed by conventional cytogenetic analysis,
and do not appear to carry prognostic value [17].
15.2.2 Outcome of Adult L3ALL Treated with
Conventional ALL Regimens
A relatively large number of small series of L 3ALL (with
3–10 patients) treated with conventional ALL regimens
have been reported, and their results have been uniformly
poor [17–26]. Conventional ALL treatments,
usually combining vincristine (VCR) an anthracycline
(ANTHR), prednisone (PR), L asparaginase (L-ASP)
and 5–6 intrathecal injections of MTX (the latter being
mainly given during consolidation therapy) yielded CR
rates of only 30–50%, with most patients subsequently
relapsing, especially in the CNS. In addition to rapid
progression in many patients, failure to achieve CR
was often due to early death associated with acute tumor
lysis syndrome. We also observed, in some cases
treated with conventional protocols, eradication of marrow
blasts but concomitant rapid progression of CNS
disease, leading to early death [18]. Median survival,
in those series, did not exceed a few months and almost
no patients were cured.
Due to similar poor results in disseminated BL and
L 3ALL in children, several pediatric groups, especially
the St. Jude’s group, the BFM German group and the
French SFOP attempted new strategies which dramatically
improved prognosis in children.
15.3 Improved Strategies in the Treatment
of Disseminated BL and L 3ALL in Children
Experience accumulated over the years by pediatric
groups had indeed shown that “classical” ALL regimens,