MULTIINSTITUTIONAL STUDY OF ALL-TRANS-RETINOIC ACID AS A DIFFERENTIATION THERAPY OF REFRACTORY ACUTE PROMYELOCYTIC LEUKEMIA

We treated 70 acute promyelocytic leukemia (APL) patients with daily o ral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemothe rapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable pat ients achieved complete remission (CR). Initial peripheral leukemia ce ll counts were significantly less in the CR cases (p < 0.01); < 100/mu l in 17 out of 18 CR cases, and greater-than-or-equal-to 200/mul in al l failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/mul, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 3 6 (86%) achieved CR. Morphological evidence of differentiation was not ed in all CR cases. Patients achieving CR received standard consolidat ion and maintenance chemotherapies, and the 20-month predicted disease -free survival rate is 76% for cases achieving their first CR with ATR A. Toxicities attributable to ATRA were minimal and included cheilitis , xerosis, dermatitis, gastrointestinal disorders, bone pain, liver da mage, and high serum triglyceridemia.