Devita, Hellman, and Rosenberg's Cancer

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LWBK1006-31 LWW-Govindan-Review December 12, 2011 19:43


444 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

pathways leading to growth and proliferation. Important targets of dif-
ferentiation mutations include core-binding factors (RUNX1 or AML1,
CBF), retinoic acid receptor alpha, HOXA9, and MOZ. Mutations in
these transcripts (frequently resulting from balanced chromosomal rear-
rangements) result in blocks in differentiation. Current paradigms sug-
gest that leukemia requires both a differentiation block and a dysregu-
lated proliferation. Thus, the common combination of FLT3-ITD and the
t(15;17) PML-RARtranslocation may be involved in APL leukemogen-
esis, whereas the other combinations are each within the same functional
group.

Answer 31.5. The answer is C.
Diffuse alveolar hemorrhage is a rare complication of induction ther-
apy in AML, which carries significant mortality risk. However, it is most
commonly reported in patients with AML and myelomonocytic or mono-
cytic features (M4 or M5). These myelomonoblasts and monoblasts dis-
play a predilection for tissue invasion, such as in the gums, as well as
into the lungs. This is thought to result from their high expression of
adhesion molecules: intercellular adhesion molecule and vascular cell
adhesion molecule. During initial treatment, activation and death of
circulating blasts may lead to pulmonary inflammation and alveolar
hemorrhage. Because of the rarity of such events, treatment options
remain poorly studied. In small series, high-dose steroids have shown
benefit.

Answer 31.6. The answer is B.
AML, which has evolved from MDS, is especially recalcitrant to ther-
apy. It may be associated with –5 or –7 cytogenetic abnormalities but
is most commonly associated with complex cytogenetics. This patient
is presenting with many poor-risk features (age>60 years, symptoms
suggestive of leukostasis, and underlying organ insufficiency), which will
make response to therapy difficult.

Answer 31.7. The answer is D.
There are many prognostic factors for AML. Of particular note are age,
cytogenetics, and performance status. Age greater than 65 years has been
associated with worse outcomes independently of cytogenetics. AML
evolving from prior MDS also confers a worse prognosis. Leukostasis
at presentation presents significant early morbidity and mortality, espe-
cially in an older patient. An elevated peripheral blast count, which may
be associated with leukostasis, is also associated with a poor long-term
prognosis.

Answer 31.8. The answer is A.
AML prognosis is currently separated into three broad categories
based on cytogenetic results: favorable (inv[16];t[8;21] andt[15;17]);
intermediate (normal, +8); and unfavorable (–5, –7, complex with
≥5 chromosomes involved). Some studies have also included 11q,
+8, del(20q), t(6;9), and 17pabnormalities in the unfavorable risk
group.
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