LWBK1006-32 LWW-Govindan-Review November 24, 2011 11:28
Chapter 32•Chronic Leukemias 455Other less common chromosomal abnormalities occur, such as 11q dele-
tion, trisomy 12, and 17p deletion. Of these, 11q and 17p deletions tend
to present at more advanced stages and follow more aggressive courses.
Early investigations have noted that approximately 50% of patients have
unmutated VH genes, which has been associated with a poorer prognosis
in retrospective analyses compared with cohorts with mutated VH genes.
Further investigation noted that patients with unmutated VH genes had
high expression of the T-cell receptor signal transduction protein, ZAP-
70.Answer 32.8. The answer is A.
This patient has Rai stage I CLL as evidenced by her lymphadenopathy,
lack of splenomegaly, and lack of anemia or thrombocytopenia, placing
her at intermediate risk. Her flow cytometry studies are typical of CLL.
Despite the diagnosis of CLL, immediate treatment in this situation is not
warranted. It is believed that CLL is not curable with current treatment
approaches, so treatment is directed at symptomatic disease or patients
who are likely to have poor prognosis. Most patients with CLL will have
a prolonged course, and many studies have demonstrated that treatment
with combinations of therapies can prolong progression-free survival and
increase response rates compared with single-agent therapies, but no sur-
vival advantage has been noted in early intervention trials. Continued
observation of patients with early-stage disease with attention to prog-
nostic factors, such as lymphocyte doubling time, ZAP-70 expression,
and karyotype, is indicated.Answer 32.9. The answer is C.
Because CLL can be a heterogeneous disease, the National Cancer
Institute-sponsored Working Group has established guidelines address-
ing indications to initiate treatment of patients. These include constitu-
tional symptoms attributable to CLL, including weight loss of greater
than 10% of baseline weight within the preceding 6 months, extreme
fatigue, Eastern Cooperative Oncology Group performance status of 2 or
greater, temperature greater than 38◦C or 100.5◦F for at least 2 weeks,
or night sweats without evidence of infection; evidence of progressive
bone marrow failure characterized by the development or progression of
anemia or thrombocytopenia, or both; autoimmune hemolytic anemia or
autoimmune thrombocytopenia, or both, which are poorly responsive to
corticosteroid therapy; massive or progressive splenomegaly; massive or
progressive lymphadenopathy; progressive lymphocytosis, defined as an
increase in the absolute lymphocyte count by greater than 50% over a
2-month period, or a lymphocyte doubling time predicted to be less than
6 months. Diagnosis of hypogammaglobulinemia is not an indication for
initiation of therapy.Answer 32.10. The answer is C.
Studies of chemotherapy regimens in CLL have repeatedly demonstrated
the activity and tolerability of the purine analog fludarabine as the most
effective single-agent chemotherapy. Not surprisingly, this agent has been
used as the backbone of other combination regimens in clinical trials. With