Devita, Hellman, and Rosenberg's Cancer

LWBK1006-33 LWW-Govindan-Review November 24, 2011 11:25

Chapter 33•Myelodysplastic Syndromes 461

ANSWERS

Answer 33.1. The answer is D.

Cytogenetic abnormalities that confer a good prognosis in patients

with MDS include del(5q), del(20q), and –Y. Abnormalities in chromo-

some 7 and complex abnormalities are associated with poor prognosis.

Intermediate-risk cytogenetics include all the other cytogenetic abnormal-

ities, which cannot be classified as good or poor.

Answer 33.2. The answer is B.

The three prognostic variables used in the IPSS for MDS are percentage

of marrow blasts, karyotype, and number of cytopenias. The overall IPSS

score is based on the sum of the scores for these three variables.

Answer 33.3. The answer is C.

This woman has 5q- syndrome. The typical presentation is refractory

macrocytic anemia in a woman, with normal or elevated platelet count

and normal white blood cell count. Bone marrow biopsy reveals dysery-

thropoiesis and hypolobulated megakaryocytes and cytogenetics show

del(5q). Patients with 5q- syndrome have a good prognosis and respond

to lenalidomide.

Answer 33.4. The answer is D.

A limitation of the IPSS is that it does not distinguish patients with severe

or moderate degrees of cytopenias, which may influence outcome. Fur-

thermore, it includes patients with 21% to 30% blasts, which would be

defined as AML per the WHO system. Normal cytogenetics are consid-

ered to be intermediate risk on karyotype scoring.

Answer 33.5. The answer is A.

Somatic mutations in AML1/RUNX1 are common in therapy-related

MDS. JAK2 mutations are seen in less than 5% of patients with MDS,

but are common in myeloproliferative diseases such as polycythemia vera

and essential thrombocytosis. c-kit mutations are seen in 13% of high-risk

MDS, and are thought to play a role in transformation to AML.

Answer 33.6. The answer is C.

Alkylating agents are associated with therapy-related MDS. This usually

occurs 3 to 7 years after treatment and carries a poor prognosis. Most

patients (90%) have monosomy 5/del (5q) and/or monosomy 7/del (7q).

Answer 33.7. The answer is A.

Inhibitory cytokines and increased apoptosis contribute to the develop-

ment of MDS. Bone marrow cells from patients with MDS have increased

expression of Fas and Fas ligand. TNF-is thought to play a role, and anti-

TNF-therapy results in increased numbers of hematopoietic colonies.

Spontaneous release of mitochondrial cytochrome c in patients with MDS

may result in activation of caspase-9, triggering the apoptotic pathway.