Evaluation of minimal residual disease in patients with chronic myeloid leukaemia on IFN-alpha 2b therapy using conventional cytogenetics and fluorescence in situ hybridization.
BACKGROUND
Chronic myeloid leukaemia (CML) is a haematopoietic malignancy characterized by the presence of the Philadelphia (Ph) chromosome that results from balanced reciprocal translocation between chromosomes 9 and 22 leading to the formation of the bcr/abl fusion gene. Studies have shown that interferon-alpha (IFN-alpha) therapy induces both cytogenetic (reduction in Ph+ cells) and molecular response (reduction in the bcr/abl positive cells) in a large proportion of patients, thereby improving their prognosis and survival. There are no reports available from India on the clinical management of CML patients using IFN-alpha therapy and molecular methods for the evaluation of residual disease. We evaluated the efficacy of IFN-alpha 2b therapy bysequential cytogenetic and molecularanalysis.


METHODS
Karyotypingwas done from G-banded metaphases obtained from 24-hour culture of bone marrow aspirates of 45 patients. Cytogenetic analysis was repeated at intervals of 4-6 months during the course of IFN-alpha therapy. Dual-colour fluorescence in situ hybridization (FISH) analysis using specific probes for bcr and abl genes was done to assess the molecular response.


RESULTS
Eight patients achieved complete cytogenetic response with no Ph+ cells. Using FISH analysis, 4 of these patients were negative for the fusion gene implying a complete response, while the remaining 4 patients showed bcr/abl fusion signals that represent residual disease.


CONCLUSIONS
Our study emphasizes the need for sequential cytogenetic and molecular analysis in the management of patients with CML and for the evaluation of minimal residual disease in patients on IFN-alpha therapy.
Talwar
Rashmi
R
All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
Choudhry
V P
VP
Jobanputra
Vaidehi
V
Kucheria
Kiran
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003561:Cytarabine; D016044:Fusion Proteins, bcr-abl