Significance of increasing levels of minimal residual disease in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic response.
OBJECTIVE
The aim of this study was to evaluate the clinical relevance of increases in quantitative polymerase chain reaction (QPCR) levels in patients with chronic myelogenous leukemia (CML) who are in complete cytogenetic response (CGCR) on therapy. Patients with Philadelphia chromosome (Ph)-positive CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by QPCR studies for minimal molecular disease. The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain.


METHODS
One hundred sixteen patients in durable CGCR, and on imatinib therapy for at least 18 months, had increases in QPCR levels (documented at least twice consecutively) as defined by literature reports. These were further analyzed by the achievement of major molecular response (MMR) defined as QPCR < or = 0.05%, as well as by the degree of increase in QPCR.


RESULTS
Only 11 (9.5%) of 116 patients with increases in QPCR had CML progression; 10 of them were among 44 patients (23%) who either lost a MMR or never had a MMR, and had more than 1 log increase of QPCR.


CONCLUSIONS
Most patients with increases in QPCR remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have more than 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions.
Kantarjian
Hagop M
HM
Department of Leukemia, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. hkantarj@mdanderson.org
Shan
Jianqin
J
Jones
Daniel
D
O'Brien
Susan
S
Rios
Mary Beth
MB
Jabbour
Elias
E
Cortes
Jorge
J
D001549:Benzamides; D002423:Cause of Death; D015331:Cohort Studies; D003582:Cytogenetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011336:Probability; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl