Quantitative reverse transcription polymerase chain reaction should not replace conventional cytogenetics for monitoring patients with chronic myeloid leukemia during early phase of imatinib therapy.
OBJECTIVE
Imatinib is the new standard drug treatment for patients with chronic myelogenous leukemia (CML). Quantitative reverse transcription-polymerase chain reaction (qPCR) for detection of BCR-ABL transcripts is frequently used for monitoring patients in addition to or instead of conventional cytogenetics, although its place in the overall diagnostic framework is not yet clear. In this study, we compared qPCR and conventional cytogenetics for monitoring of patients during the early phases of imatinib therapy.


METHODS
One hundred and seventeen patients treated with imatinib for CML in chronic or accelerated phase were prospectively followed with qPCR and karyotyping. Comparisons were made between both methods and between qPCR results from bone marrow and peripheral blood. To determine the prognostic impact of qPCR and cytogenetics during the early phase of imatinib treatment on subsequent cytogenetic response and progression-free survival (PFS), a multivariate model was generated that included established prognostic baseline variables.


RESULTS
We found a significant correlation between the proportion of Philadelphia (Ph) chromosome-positive metaphases and qPCR in the bone marrow and peripheral blood. Low qPCR values after 3 months of therapy were correlated with major cytogenetic response (MCyR) at 6 months and PFS at 2 years. However, in multivariate analysis, the cytogenetic response at 3 months emerged as the only independent parameter predictive of MCyR at 6 months and PFS at 2 years.


CONCLUSIONS
Our data suggest that conventional karyotyping should remain the standard method for following patients on imatinib during the early phases of therapy.
Lange
Thoralf
T
Department of Hematology, University of Leipzig, Germany.
Bumm
Thomas
T
Otto
Sandra
S
Al-Ali
Haifa-Kathrin
HK
Kovacs
Ines
I
Krug
Daniela
D
Köhler
Thomas
T
Krahl
Rainer
R
Niederwieser
Dietger
D
Deininger
Michael W N
MW
D000328:Adult; D000368:Aged; D001549:Benzamides; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D020732:Cytogenetic Analysis / Q000379:methods* / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000097:blood / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence / Q000379:methods / Q000706:statistics & numerical data; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods* / Q000706:statistics & numerical data
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D016044:Fusion Proteins, bcr-abl