Devita, Hellman, and Rosenberg's Cancer

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

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

Answer 31.24. The answer is C.

Attempts have been made to shorten maintenance therapy to 12 to

18 months, with inferior results. Current recommendations are for 2 to

3 years.

Answer 31.25. The answer is A.

Philadelphia chromosome positive ALL carries a high-risk prognosis,

but this has improved with the ABL tyrosine kinase inhibitor imatinib.

Second-generation inhibitors such as dasatinib and nilotinib may also

prove of value in the future. Alemtuzumab is an anti-CD52 monoclonal

antibody that has demonstrated significant efficacy in the treatment of

CLL. It has not been evaluated in ALL, which typically does not express

CD52. Gemtuzumab ozogamicin is an anti-CD33 monoclonal antibody

cross-linked to a cytotoxin, calicheamicin. It has been shown to improve

outcomes in relapsed AML. Sunitinib is a nonspecific tyrosine kinase

inhibitor. It has significant activity against FLT3 and may prove of value

in the treatment of AML with FLT3-ITD.

Answer 31.26. The answer is B.

Stem cell transplantation for AML remains a developing field. Current

studies and meta-analysis have not found benefit in CR1 for patients

with favorable cytogenetics (e.g., inv[16] andt[15;17]). Benefit is uncer-

tain in patients with normal cytogenetics. Future trials may be able to

assess the benefit of transplant in CR1 in higher-risk subpopulations of

normal cytogenetics (e.g. FLT3-ITD or DNMT3A mutations). Patients

aged less than 55 years who have unfavorable cytogenetics (e.g., –5, –7,

complex cytogenetics) appear to benefit from myeloablative transplanta-

tion in CR1. However, older patients tolerate this approach less well, with

increased treatment-related morbidity and mortality. Decision making in

older patients must be individualized, and nonmyeloablative transplant

approaches are being explored.

Answer 31.27. The answer is B.

NPM1 gene encodes a protein that functions as a molecular chaperone

between the nucleus and cytoplasm. Mutations involving this gene are

found in 50% to 60% of all AML patients with normal karyotype. Aber-

rant cytoplasmic localization of NPM1 is associated with point mutations

in the gene. In the absence of FLT3-ITD, the NPM1 mutation is associated

with favorable prognosis.