Devita, Hellman, and Rosenberg's Cancer

LWBK1006-32 LWW-Govindan-Review November 24, 2011 11:28

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

imatinib-resistant mutations have outcomes that are similar to what

would be expected in clinically advanced disease.

Answer 32.5. The answer is D.

Allogeneic hematopoietic stem cell transplantation is the only poten-

tially curative therapy in CML. Induction of molecular remission after

transplantation is more durable than that obtained with imatinib alone.

After allogeneic hematopoietic stem cell transplantation, evidence of the

leukemic clone can be detected in many patients, but will disappear over

time, with very few patients continuing to have molecular evidence of

CML at 2 years when undergoing transplantation in the chronic phase.

The relapse rate after transplantation in the chronic phase is less than

10% in most series with greater than 50% of relapses occurring within

the first year and less than 5% occurring after the fifth year.

Early intervention at first documentation of relapse confers the greatest

chance of controlling the disease. Initial institution of imatinib 400 mg

daily can restore complete molecular remission in 83% of patients with

molecular relapse and 56% of patients with cytogenetic relapse. Up to

25% of patients who attain a complete molecular remission can be with-

drawn from the imatinib therapy within 6 to 24 months, whereas others

may require long-term therapy with imatinib or donor leukocyte infu-

sions (DLIs). Because of the exquisite sensitivity of CML to graft-versus-

leukemia effects, patients who relapse into chronic phase by cytogenetics

or hematologic criteria, 60% to 80% can be treated with DLI alone with

5-year disease-free survival rates of 50%. Patients who relapse again after

initial DLI can often be retreated with DLI as well. However, DLI car-

ries significant risks with treatment-related mortality of 8% to 20% and

adverse effects of acute and chronic GVHD, infectious complications, and

others.

Answer 32.6. The answer is D.

Imatinib was the first tyrosine kinase inhibitor approved for treating

patients diagnosed with chronic-phase CML. Two newer tyrosine kinase

inhibitors, nilotinib and dasatinib, are more potent inhibitors of BCR-

ABL kinase than imatinib, and were initially developed for use in patients

with resistance or intolerance to imatinib. They both have recently been

approved by the FDA for treating patients with newly diagnosed Ph+

chronic-phase CML, based on randomized trials comparing these agents

with imatinib in the first-line setting, which demonstrated superiority of

the newer agents in the rates of major molecular response.

Answer 32.7. The answer is B.

Much insight has been gained into the molecular abnormalities associated

with CLL. Various chromosomal abnormalities can be reliably detected

by FISH, with greater than 80% of cases demonstrating abnormalities.

The most commonly encountered abnormality is a deletion of chromo-

some 13q, found in approximately 55% of cases. Further investigation of

this common abnormality has led to the observation that this is often asso-

ciated with deletion or downregulation of two microRNA genes (miR15

and miR16), which may downregulate the antiapoptotic protein, bcl-2.