title: The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.
abstract: This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2-3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions.
authors.affiliation: University of Chicago Medical Center, IL 60637-1470.
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: R S
authors.initials: RS
authors.lastname: Day
authors.forename: N
authors.initials: N
authors.lastname: Azarnia
authors.forename: J M
authors.initials: JM
authors.lastname: Bennett
authors.forename: G
authors.initials: G
authors.lastname: Browman
authors.forename: J
authors.initials: J
authors.lastname: Goldberg
authors.forename: A
authors.initials: A
authors.lastname: Gottlieb
authors.forename: H
authors.initials: H
authors.lastname: Grunwald
authors.forename: K
authors.initials: K
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Raza
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000677:Amsacrine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000677:Amsacrine; D003561:Cytarabine