Circulating immune complexes correlate with remission duration in acute myeloid leukemia.
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.
Larson
R A
RA
Department of Medicine, University of Chicago, IL.
Lukin
C L
CL
Daly
K M
KM
Mick
R
R
Gore
S
S
Le Beau
M M
MM
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
D000936:Antigen-Antibody Complex; D003561:Cytarabine; D004317:Doxorubicin; D015922:Complement C1q; D003630:Daunorubicin