Trial Information

Collection of Blood and Bone Marrow Samples From Select Patients With CML to Measure Minimal Residual Disease

Although allogeneic stem cell transplantation is curative in CML, evidence of the BCR-ABL
oncogene at low levels is still found in long-term follow-up of survivors. Such low levels
of BCR-ABL post-transplant, which do not fulfill criteria for molecular relapse are
monitored regularly and considered to be suppressed by the GVL effect. Treatment with donor
lymphocyte infusions is only instituted when quantifiable BCR-ABL transcript levels rise
steadily, indicative of a true molecular relapse."

Similarly, BCR-ABL is still detectable in the majority of CML patients treated with imatinib
who achieve complete cytogenetic response, although the amount of BCR-ABL transcripts seem
to decline with longer follow-up. With 5 years follow-up of CML patients at CP who received
imatinib, the estimated cumulative best rates of complete hematologic response and complete
cytogenetic response were 98 percent and 87 percent, respectively 10. For the minority of
CP-CML patients who do not respond satisfactorily to imatinib, second-generation tyrosine
kinase inhibitors are now the recommended next line of treatment.

A major question facing clinicians is whether imatinib and the other more pharmacologically
potent second-generation tyrosine kinase inhibitors can suppress the CML clone at the
leukemic stem cell level as effectively as allogeneic stem cell transplantation. This
protocol is designed to scientifically compare the treatment responses of patients who are
treated with allogeneic stem cell transplantation with patients who receive imatinib or
second generation tyrosine kinase inhibitors.

The primary endpoint of this trial will be the proportion of patients who have detected
minimal residual disease (DMRD) in primitive CD34 plus progenitor subpopulations no earlier
than 60 days from the onset of their respective treatments.