URINARY-EXCRETION OF PROTEOLYZED ALPHA(1)-ANTITRYPSIN - SPECIFICITY, QUANTITATION, AND RELATION TO THERAPY RESPONSE IN PATIENTS WITH ACUTE MYELOID-LEUKEMIA

During remission induction chemotherapy, a 41-kDa cleavage product of alpha(1)-antitrypsin (alpha(1)-AT(41)) can be found in the urine of pa tients with acute myeloid leukemia, By using immunoblotting with antib odies against this protein, 27 patients with acute myeloid leukemia we re screened for the excretion of this fragment and the amount of alpha (1)-AT(41) compared with treatment response assessed by therapy-induce d cytoreduction in the bone marrow and time to reach remission, Patien ts with acute lymphoblastic leukemia, malignant lymphomas, and solid t umors receiving chemotherapy, patients with nonmalignant diseases like sepsis and kidney dysfunction, and healthy subjects were probed to ev aluate the specificity of this phenomenon, In 74% of the acute myeloid leukemia patients, the truncated inhibitor was detected, Mean concent ration of peak excretion was found to be 6.7 mu g/mg creatinine (range , 1.1-41 mu g/mg). Among the patients treated with induction chemother apy, those who responded completely (<5% residual marrow blast cells) exhibited significantly higher alpha(1)-AT(41) concentrations than the nonresponders (P < 0.03), Patients who showed a partial response (6-2 5% residual blasts) excreted intermediate values of the protein, The p robability of median time to reach remission was 40 days in patients e xcreting the truncated inhibitor in measurable amounts compared to 100 days in patients negative for alpha(1)-AT(41) (P < 0.02), The 41-kDa fragment was also found in one of 10 patients with acute lymphoblastic leukemia and in 3 of 18 lymphoma patients but not in those with solid tumors, infections, or kidney disease or in healthy individuals.