Korean J Hematol.  2002 Feb;37(1):1-8.

Quantitative Assessment of Philadelphia Chromosome Using Interphase/Hypermetaphase FISH and Toxicity after STI571 Treatment in Chronic Myelogenous Leukemia

• Lee KE
• Im SA
• Yoo ES
• Ahn JY
• Lee SM
• Huh JW
• Lee SN
• Chung WS
• Seong CM

Abstract

BACKGROUND: Chronic Myelogenous Leukemia (CML) is the first proven disease in which gene abnormality, t(9;22)(q34;q11) can cause the disease to occur in humans. Recently, targeted therapy with STI571 (GleevecTM), signal transduction inhibitor for BCR-ABL kinase was developed and can induce cytogenetic remission in patients with CML. Hypermetaphase-FISH (HMF)/Interphase-FISH (I-FISH, Fluorescence in situ hybridization) aiming specific chromosomal abnormalities are unambiguous quantitative molecular genetic methods for individual Philadelphia (Ph1) chromosome positive cells. We evaluated the change of Ph1 chromosome in CML patients during STI571 therapy using HMF/I- FISH.
METHODS
Twenty one patients with CML were treated with STI571 which was provided from Norvatis pharmaceutical company as Expanded Access Program for Compassionate Use from May 2001 at the doses of 200-600 mg/day orally. Median age of this cohort was 37 years old and median follow up duration was 113 days (48~165 days). HMF or I-FISH using bone marrow or peripheral blood were performed on the sample at baseline, day 14, day 28 and then monthly.
RESULTS
Complete cytogenetic responses which were assessed by HMF/I-FISH counting several hundreds cells were found in 8 of 21 patients. Among them, 4 of 10 chronic phase, 2 of 2 accelerate phase and 2 of 8 blastic crisis patients achieved cytogenetic complete response. One patient with blastic crisis was relapsed after achieving cytogenetic complete response. Grade III-IV thrombocytopenia and neutropenia were noticed in 8 and in 7 patients respectively, but there were no major bleeding episodes nor neutropenic fever.
CONCLUSION
BCR-ABL tyrosine kinase inhibitor, STI571 was tolerable for patients with CML. The majority of patients achieved hematologic remission and 8 out of 21 patients achieved complete cytogenetic response regardless of their disease stage. Cytogenetic response of Ph1 chromosome can be quantified accurately with HMF/I-FISH.

Keyword

CML (Chronic myelogenous leukemia); STI571 (GleevecTM); FISH (Fluorescence in situ hybridization); Philadelphia (Ph1) chromosome

MeSH Terms

Adult
Bone Marrow
Chromosome Aberrations
Cohort Studies
Compassionate Use Trials
Cytogenetics
Fever
Fluorescence
Follow-Up Studies
Fusion Proteins, bcr-abl
Hemorrhage
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*
Molecular Biology
Neutropenia
Philadelphia Chromosome*
Phosphotransferases
Signal Transduction
Thrombocytopenia
Imatinib Mesylate
Fusion Proteins, bcr-abl
Phosphotransferases