OUTCOME OF INTENSIVE CHEMOTHERAPY FOR ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA - A POSSIBLE DOSE-EFFECT

Fifty consecutive adult patients with acute lymphoblastic leukemia (AL L) were treated with an intensive cyclical chemotherapy and the mean r eceived dose of individual cytotoxic drug was retrospectively studied. The median age was 28 years. Twenty-one (43%) had white blood cell (W BC) count over 30 x10(9)/l. Of the 26 patients with successful cytogen etic studies, ten (28%) had unfavorable clonal chromosomal abnormaliti es (four Philadelphia chromosome, six others). A high complete remissi on (CR) rate (86%) was achieved. This was associated with delivery of 100% of the planned dosage of vincristine, prednisone, and daunorubici n at induction. Dose reduction of asparaginase, the fourth drug in the induction protocol, was recorded in 20 (40%) patients. The CR rate of these patients was not adversely affected. Dose reduction was recorde d during consolidation (38 of 43 remitters) and maintenance (18 of 20 remitters) as a result of treatment toxicity. The mean received dose o f teniposide, Ara-C, asparaginase, mercaptopurine, and methotrexate wa s 73% (SD 7%), 73% (SD 7%), 62% (SD 41%), 65% (SD 15%) and 73% (SD 17% ) of the planned dosage, respectively. The 5-year overall survival and leukemia-free survival (LFS) were 11%(95% CI: 0-27%) and 13% (95% CI: 0-26%), respectively. Even standard-risk patients had 4-year LFS of o nly 26% (95% CI: 0-57%). Among 36 remitters not withdrawn from consoli dation, there were 29 treatment failures after a median follow-up of 4 2 months; 25 (86%) of these were leukemia relapse, three (10%) were to xic death during consolidation, and one patient (4%) died from therapy -related myelodysplastic syndrome. We postulate inadequate drug delive ry during postremission therapy contributed to the high relapse rate i n the whole group as well as the standard-risk patients.