Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy.
Therapy-related MDS and AML are complications of intensive chemotherapy regimens. Traditionally, patients exposed to topoisomerase II inhibitors are reported to develop secondary AML with abnormalities of chromosome 11q23. We evaluated the long-term hematologic toxicity of topoisomerase II-intensive high-dose mitoxantrone-based chemotherapy in 163 newly diagnosed acute leukemia patients treated over an 8 year period. Nine (5.5%) patients developed new cytogenetic abnormalities. Four patients developed MDS with progression to AML, three patients developed new abnormalities at the time of relapse, and three patients (including one of the former patients) had changes that were not associated with hematologic disease. The abnormalities most frequently involved chromosomes 7q, 20q, 1q, and 13q. Despite the use of topoisomerase II-intensive treatment, no patient developed an abnormality involving chromosome 11q23. Spontaneous resolution of some changes and prolonged persistence of others in the absence of hematologic disease indicates that some cytogenetic changes are not sufficient to promote leukemogenesis.
Seiter
K
K
Department of Medicine, Division of Oncology/Hematology, New York Medical College, New York, NY, USA.
Feldman
E J
EJ
Sreekantaiah
C
C
Pozzuoli
M
M
Weisberger
J
J
Liu
D
D
Papageorgio
C
C
Weiss
M
M
Kancherla
R
R
Ahmed
T
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015994:Incidence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012189:Retrospective Studies; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D059005:Topoisomerase II Inhibitors; D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin