Emergence of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases.
New treatments which may change the course of a disease, or which have potential carcinogenicity, may result in the development of new cytogenetic or clinical disorders. Three patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia (CML) who developed new cytogenetic abnormalities after achieving a cytogenetic complete remission (CR) of their Ph-positive disease with interferon alpha (IFN-alpha) based therapy are described. Patient 1 developed chromosomal abnormalities involving chromosomes 5 (5q13-34) and later 7 (monosomy 7) 60 months after the start of therapy and 20 months after IFN-alpha was discontinued. A myelodysplastic syndrome was noted 83 months from the start of therapy. Patient 2 developed a myeloproliferative syndrome with 18p11 chromosomal abnormalities 90 months after the start of the therapy and 60 months after IFN-alpha was discontinued. Patient 3 developed a chromosome 11 abnormality (11q21-23) 23 months after the start of therapy, without hematological manifestations. All three patients remain in cytogenetic CR of Ph-positive disease with the hypermetaphase fluorescent in situ hybridization and polymerase chain reaction studies for BCR/ABL showing minimal residual disease. The emergence of new cytogenetic or clinical disorders in patients with CML on IFN-alpha therapy needs to be monitored. These findings may be related to changing the natural course of CML, to therapy, or to the emergence of suppressed clones in a stem cell disorder.
Fayad
L
L
Department of Hematology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Kantarjian
H
H
O'Brien
S
S
Seong
D
D
Albitar
M
M
Keating
M
M
Talpaz
M
M
D000368:Aged; D001803:Blood Transfusion; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins