LWBK1006-32 LWW-Govindan-Review November 24, 2011 11:28
Chapter 32•Chronic Leukemias 453ANSWERS
Answer 32.1. The answer is B.
Nonhematologic toxicities are the most frequently observed toxicities dur-
ing treatment with imatinib and include nausea, diarrhea, muscle cramp-
ing, edema, rashes, and fatigue. Grade 3 or 4 myelosuppression occurs in a
minority of treated patients and is the result of the predominant Philadel-
phia chromosome positive stem cell clone that is driving the majority of
the hematopoiesis. The appropriate therapy is to interrupt the dose if the
absolute neutrophil count decreases to less than 1.0× 109 /L or platelets
decrease to less than 50× 109 /L. Dose reductions are not appropriate
because the normal hematopoiesis is minimally affected by imatinib and
may allow for emergence of resistant clones.Answer 32.2. The answer is D.
Cytogenetic responses on imatinib therapy have a significant impact of
disease progression. Of patients who achieve a complete cytogenetic
response to imatinib therapy at 12 months, 97% will not progress to the
accelerated phase or blast crisis. For patients with a partial cytogenetic
response, the estimate is 93%. Sokal risk score at diagnosis predicts rate of
complete cytogenetic response: patients with a low-risk Sokal score have
a 93% rate of complete cytogenetic response, compared with an 81% rate
in patients with a high-risk Sokal score. For patients who obtain a com-
plete cytogenetic response, pretreatment Sokal scores are not predictive
of disease progression at 5 years.Answer 32.3. The answer is D.
Point mutations in the BCR-ABL kinase are the most common cause
of relapse in patients with CML. These mutations render the BCR-ABL
kinase less sensitive to imatinib. Other mechanisms mediating disease
relapse include BCR-ABL gene amplification, drug efflux, and finally
clonal evolution.Answer 32.4. The answer is C.
Although allogeneic stem cell transplantation is the only potentially cura-
tive therapy in CML, most patients with chronic-phase disease are treated
with imatinib therapy initially. Concerns have been raised that exposure
to such kinase inhibitors could result in poorer outcomes if patients were
to later proceed with stem cell transplantation as was demonstrated with
prolonged exposure to interferon. Large observational studies have sug-
gested that there is no detrimental effect to prior imatinib exposure in
patients proceeding with stem cell transplantation. These patients do
tend to undergo transplant with more advanced stages of disease and
higher EBMT scores, but there has been no evidence for inferior overall
survival, disease-free survival, transplant-related mortality, acute graft-
versus-host disease (GVHD), engraftment kinetics, or organ toxicity com-
pared with patients who were not exposed to imatinib before transplant.
Furthermore, in small case studies, it appears that patients harboring