LONG-TERM FOLLOW-UP OF HEMOSTATIC MOLECULAR MARKERS DURING REMISSION INDUCTION THERAPY WITH ALL-TRANS-RETINOIC ACID FOR ACUTE PROMYELOCYTICLEUKEMIA

Hemostatic molecular markers were serially monitored in a prospective fashion during remission induction therapy with all-trans retinoic aci d (ATRA) in sixteen patients with acute promyelocytic leukemia (APL). One patient with leukocytosis before treatment and three pa patients w ho later developed hyperleukocytosis also received chemotherapy with b ehenoyl Ara-C and daunorubicin. Plasma levels of E-fragment of fibrin and fibrinogen degradation product (FDP-E), FDP-D dimer (D-D), thrombi n-antithrombin complex (TAT), and plasmin-alpha(2) plasmin inhibitor c omplex (PIC) were markedly elevated in all but one patient before trea tment, and these parameters decreased to normal or near normal ranges in most patients within the first 7 days of treatment. Interestingly, we have found that these parameters were again elevated during the lat er course of ATRA therapy (after day +7) in eleven patients for variou s reasons including cytotoxic chemotherapy (3 cases), fever (5 cases; 2 cases with apparent infection, 3 cases without known etiology), Caes arean section (1 case), and no apparent etiology (2 cases). Three pati ents showed bleeding complications during re-elevation of molecular ma rkers, but none developed thrombosis. Plasma elastase-ol, proteinase i nhibitor complex (E-alpha(1)PI) was markedly elevated in all patients at diagnosis and did not decrease significantly during ATRA therapy. P lasma tissue factor antigen was mildly elevated in one our of four pat ients studied, and thrombomodulin was elevated in two out of ten patie nts tested. These results confirmed the rapid normalization of coagulo pathy during the early phase of remission induction therapy with ATRA but suggest that re-elevation of molecular markers occurs frequently d uring the later course of ATRA therapy.