High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF).
A study was made to determine CR rate, response duration and survival in patients with RAEB or RAEB-t given AML-type chemotherapy, in particular the newer agents idarubicin and fludarabine. Eighty-five adults (58 RAEB-t, 27 RAEB) received either IA (idarubicin 12 mg/m2 daily on days 1-3, ara-C 1.5 g/m2 daily on days 1-4 CI), FA (fludarabine 30 mg/m2 daily on days 1-5, ara-C 2 g/m2 daily on days 1-5) or FLAG (FA + G-CSF 400 micrograms/m2 daily from day-1 until CR). IA was given exclusively to patients with better prognosis (as assessed by pretreatment karyotype), while FA and FLAG were given first to patients with worse and then to those with better prognosis. In remission, patients received lower doses of the same regimens for 6-12 months. The 85 patients comprise the largest reported series of RAEB or RAEB-t patients given AML-type chemotherapy. Their median age was 61 years, 33% had chromosome 5 or 7 abnormalities (-5/-7), and 55% were treated in laminar air flow rooms. The CR rate was 66%. While rates were highest in younger patients with a normal karyotype, CR rates in excess of 50% were also obtained in patients over age 60 (27/47; 57%) and in patients with -5/-7 (17/29; 59%). In 11 of the 14 cytogenetically abnormal patients in whom cytogenetic analysis was repeated at the time of CR, only normal metaphases were found. In the remaining 3 the number of abnormal metaphases was substantially reduced. However, the probability of continued CR was low (e.g. 452 +/- 0.08 at 12 months), and the only patients alive in CR beyond two years were patients under age 60 without -5/-7 and with RAEB-t. Survival probability was 0.35 +/- 0.05 at one year. Eight of 56 patients died in CR. While current AML-type chemotherapy can produce higher CR rates than is perhaps usually appreciated, in some patients with RAEB or RAEB-t (e.g. older patients with -5/-7) the brevity of the remissions and the risk entailed suggest that new post-remission therapies are needed to make this approach generally worthwhile.
Estey
E H
EH
Department of Hematology, University of Texas MD Anderson Cancer Center, Houston, USA.
Kantarjian
H M
HM
O'Brien
S
S
Kornblau
S
S
Andreeff
M
M
Beran
M
M
Pierce
S
S
Keating
M
M
D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D016001:Confidence Intervals; D003561:Cytarabine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004780:Environment, Controlled; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008875:Middle Aged; D010976:Platelet Count; D011336:Probability; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin