Devita, Hellman, and Rosenberg's Cancer

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.