CHANGES IN MICRORHEOLOGY OF ACUTE PROMYELOCYTIC LEUKEMIA-CELLS DURINGALL-TRANS-RETINOIC ACID (ATRA) DIFFERENTIATION THERAPY - A MECHANISM FOR ATRA-INDUCED HYPERLEUKOCYTOSIS

According to French and European experience, hyperleukocytosis occurs during ATRA differentiation therapy in about 70% of de novo and 25% of relapsed APL cases. The most frequently suggested cause for this side -effect is an ATRA-induced proliferation of APL cells. However, no def inite explanation for such a proliferative effect has been clearly est ablished. Another mechanism directly related to the differentiation of marrow leukemic cells could be a change in their microrheology, allow ing their release from the bone marrow and their transfer toward perip heral blood (PB) and tissues. Using a single cell aspiration assay int o a glass restrictive channel, we measured APL cell viscosity values i n five de novo APL patients. A deformability index (DI) was defined as the ratio of mean normal neutrophil viscosity x 100/mean APL cell vis cosity. Results were the following: (1) at diagnosis, two patients had high marrow DI (96 and 250%) and three patients had low marrow DI (16 , 17, and 40%); (2) when PB and marrow APL cells were simultaneously t ested, PB APL cells display higher DI than marrow APL-cells; (3) the t wo patients with high initial marrow DI experienced an ATRA-induced hy perleukocytosis after only 1 day of treatment; (4) in the three patien ts with low initial marrow DI, the DI was increasing during ATRA thera py and hyperleukocytosis seemed to occur when a large amount of maturi ng APL cells reached a viscosity value similar to that of mature neutr ophils. These results suggest that an asynchronism between theological and morphological maturation in each APL cell might explain the occur rence of hyperleukocytosis in some patients during ATRA differentiatio n therapy.