Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine.
Seventeen patients with therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.
Larson
R A
RA
Department of Medicine, University of Chicago, IL 60637.
Wernli
M
M
Le Beau
M M
MM
Daly
K M
KM
Pape
L H
LH
Rowley
J D
JD
Vardiman
J W
JW
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations / Q000188:drug therapy; D025063:Chromosome Disorders; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D012074:Remission Induction
D003561:Cytarabine