Page 1181 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 66

ACUTE LYMPHOBLASTIC LEUKEMIA IN ADULTS

Shira Dinner, Sandeep Gurbuxani, Nitin Jain, and Wendy Stock

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of Greaves and colleagues have used DNA obtained from neonatal
diseases characterized by clonal proliferation of lymphoid progenitors blood spots to demonstrate that ALL-associated chromosomal trans-
(lymphoblasts). Improved diagnostic tools permit accurate and locations (and hence a preleukemic clone) can be demonstrated in
prompt diagnosis, and aid in evaluation of minimal residual disease neonatal blood spots that are acquired in utero. Furthermore, these
(MRD). There have been significant advances in the past decade are present at 100-fold higher rate than the incidence of leukemia.
toward understanding disease pathogenesis, refinement of prognostic These investigators hypothesize that overt leukemia evolves as a
groups, and the development of exciting new therapies directed consequence of an abnormal lymphoid proliferation that occurs in
towards specific disease subsets. These molecular targeted and immu- response to exposure to an as yet unidentified infectious agent(s).
notherapeutic approaches are transforming the treatment strategies Supporting this hypothesis are data that suggest that day care atten-
for adults with ALL and are beginning to result in significant dance associated with early exposure to common infectious agents is
improvements in survival. associated with a lower incidence of ALL. Similarly, industrialization
associated with improved socioeconomic status and exposure to
common infectious agents later in life has been postulated to result
EPIDEMIOLOGY in abnormal and excessive lymphoid proliferation and leukemic
transformation. Finally, an infectious etiology can also be evoked to
It is estimated that in the year 2015, approximately 6250 new cases explain leukemic clusters that occur when a previously unexposed
of ALL will be diagnosed and 1440 deaths will occur due to the community is exposed to infectious agents brought into the com-
disease in the United States. ALL is primarily a cancer of childhood; munity by a large influx of residents, as happens during urbanization
the peak incidence (7.7 in 100,000) occurs between the ages of 1 and of rural communities. However, it needs to be reiterated that all of
4 years, and approximately 60% of the patients are diagnosed before these studies are at best correlative and not supported by direct
the age of 20 years. The incidence of ALL begins to decline with experimental evidence. Furthermore, the infectious or environmental
increasing age after the first decade of life. A second upward trend agent(s) responsible for this abnormal lymphoid proliferation remains
starts to emerge in the sixth decade of life, and a much smaller peak elusive.
is seen in patients older than 85 years of age (1.8 in 100,000). Men
have a slightly higher incidence of ALL than women (male-to-female
ratio, 1.4 : 1). The overall age-adjusted rate of ALL has increased from CLINICAL MANIFESTATIONS
0.93 in 100,000 in the year 1975 to 1.47 in 100,000 in the year
2008. Similar increases in the incidence of ALL have also been The clinical presentation of ALL encompasses a wide spectrum of
reported in Scandinavia, the United Kingdom, and Italy. Although symptoms that correlate with the degree of bone marrow (BM)
most investigators agree that this increase in the incidence is beyond involvement and the resultant cytopenias, as well as the leukemic cell
what might be expected from better reporting, the actual cause(s) of burden. Typical symptoms include fatigue, anorexia, night sweats,
this increased incidence remains largely speculative. pallor, shortness of breath, bone pain, fever, and bleeding diathesis.
Involvement of extramedullary sites may present with lymphade-
nopathy, hepatomegaly, or splenomegaly. Less commonly, ALL can
ETIOLOGY involve the central nervous system (CNS), leading to headache,
vomiting, lethargy, and cranial nerve palsies. Other extramedullary
A small minority of ALL cases (<5%) are associated with predisposing sites of involvement include the testis, tonsils, adenoids, breast, and
inherited syndromes such as Down syndrome, Bloom syndrome, gastrointestinal tract. Precursor T-cell ALL often presents with a large
ataxia telangiectasia, and Nijmegen breakage syndrome. However, the mediastinal mass with associated respiratory distress or possible signs
underlying etiology is not known in most cases. Although parental of superior vena cava syndrome. Burkitt leukemia/lymphoma is fre-
tobacco or alcohol use, exposure to pesticides or solvents, and ciga- quently associated with CNS involvement and bulky adenopathy.
rette smoking have all been implicated, only ionizing radiation has
been significantly linked to increased risk of developing ALL. The
vast majority of literature that attempts to identify causative agents CLINICAL AND LABORATORY EVALUATION
for ALL is at best correlative; most of it borders on pure speculation
and conjecture. Only recently has it been appreciated that the interac- The initial workup for patients with suspected ALL is detailed in
tion between genetic predisposition and environmental factors Table 66.1. All patients should undergo a detailed history and phys-
involved in leukemogenesis is complex and may be different for ical examination. Family history should be ascertained. Laboratory
different subtypes of ALL. Epidemiologic studies designed to identify evaluation should include complete blood count (CBC) with dif-
environmental agents involved in leukemogenesis will therefore have ferential; comprehensive metabolic panel, including liver function
to take into account the biologic subsets defined by morphology, tests, lactate dehydrogenase (LDH), and uric acid. Coagulation
immunophenotype, karyotype, and the molecular abnormalities, and profile should also be obtained, although coagulation parameters are
consider the possibility that for each of these subtypes the causative frequently normal at diagnosis. Human leukocyte antigen (HLA)
agent may well be different. To adequately investigate these issues, testing should be obtained for patients who are potential candidates
future studies will require collaborative efforts studying large patient for allogeneic stem cell transplantation (aSCT).
populations. All patients should undergo BM aspiration and biopsy for confir-
Despite the limitations described, it is relevant to review some of mation of diagnosis, and for cytogenetic and molecular genetic evalu-
the recent advances in our understanding of the etiology of ALL. ation. It is particularly important to send an aspirate (or peripheral

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