title: Circulating immune complexes correlate with remission duration in acute myeloid leukemia.
abstract: It has been suggested that circulating immune complexes (CIC) favor tumor progression by suppressing the host's immune response to malignant cells via blocking factors to cell-mediated cytotoxicity. We prospectively measured CIC by the C1q binding assay in 100 untreated patients with acute myeloid leukemia (AML) de novo. The median CIC level was 135, the range 0-1000, and the mean +/- standard error (SE) 175 +/- 18 micrograms/ml. Sixty-eight patients, termed abnormal, had C1q binding levels greater than 2SE above the mean of the normal population (61 +/- 15 micrograms/ml). There were no significant differences between the 32 patients with normal CIC and the 68 with abnormally elevated CIC in any pretreatment characteristic: gender, age, white blood cell count (WBC), platelets, leukemia cell mass, LDH, immunoglobulins, or fibrinogen. Abnormal CIC levels did not correlate with FAB morphology, the presence of a clonal chromosomal abnormality (76% of all patients), or with specific cytogenetic subgroups, although nine of 11 patients with acute promyelocytic leukemia and t(15;17) had abnormal CIC. There were no significant differences in complete remission (CR) rates after the first chemotherapy course (45 vs 40% for normal vs abnormal CIC) or after all courses of treatment (55 vs 65%). Survival from diagnosis was not significantly different for the normal and abnormal groups (9.3 vs 5.8 months, p = 0.24), but survival after achieving a CR was markedly longer for those with normal pretreatment CIC (33.8 vs 11.7 months, p = 0.0068). Pretreatment CIC strongly correlated with remission duration for the 59 patients who achieved CR (16.5 months for 17 normal patients vs 6.9 months for 42 abnormal patients, p = 0.0002). This was independent of age, WBC, leukemia cell mass, or FAB morphology. Within the lowest C1q quartile (less than 60 micrograms/ml), 43% of the patients have not relapsed with a minimum follow-up of 18 months compared to only 6-14% for the three higher quartiles. We conclude that host immunity as assessed by CIC levels has little effect on the initial response to therapy but may play a role in maintaining remission in AML.
authors.affiliation: Department of Medicine, University of Chicago, IL.
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: C L
authors.initials: CL
authors.lastname: Lukin
authors.forename: K M
authors.initials: KM
authors.lastname: Daly
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: S
authors.initials: S
authors.lastname: Gore
authors.forename: M M
authors.initials: MM
authors.lastname: Le Beau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000032:analysis*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D015922:Complement C1q / Q000378:metabolism; D003561:Cytarabine / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D003630:Daunorubicin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D000936:Antigen-Antibody Complex; D003561:Cytarabine; D004317:Doxorubicin; D015922:Complement C1q; D003630:Daunorubicin