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Treatment of acute promyelocytic leukemia in British Columbia from 1984 to 2001

Treatment of acute promyelocytic leukemia in British Columbia from 1984 to 2001

Blood 98(11 Part 2): 223b, November 16

The treatment of APL has evolved over the past 20 years to incorporate the use of all-transretinoic acid (ATRA) as directed therapy. We reviewed the charts of all adult patients diagnosed with APL treated in British Columbia from 1984 until May 2001 to assess the effects of changes in therapy. Seventy-one patients were identified with APL associated translocations or were molecularly positive for the PML-RARalpha transcript. Forty-three had t(15;17) alone, 23 had additional cytogenetic abnormalities, 4 were identified by molecular studies alone, one had t(10;17) and was also molecularly positive. Twenty-nine patients were female. Median age was 44 years (14-79yrs). Median presenting white blood cell (WBC) count was 2.2X109/L (range 0.5-151X109/L). All patients were treated with a combination of an anthracycline with cytarabine. ATRA was added as part of the standard treatment in May 1993. Forty-six of the 71 patients received ATRA. Seventeen patients developed suspected ATRA syndrome which was treated with dexamethasone. Two patients developed Sweet's syndrome as a complication of ATRA therapy. Six patients died within a month of diagnosis from complications related to the disease or treatment. Of the remaining patients only one (1.4%) never achieved a CR. This patient has t(10;17). Four patients remained cytogenetically positive in the bone marrow after count recovery from their first cycle of chemo+ATRA. All 4 achieved CR with subsequent chemo+ATRA and 3 are still in CR 16-45 months after diagnosis. The fourth patient died of anthracycline toxicity. Six patients had had a malignancy 1 to 8 years prior (4 breast, 1 testicular, 1 lymphoma). Of these, 4/6 patients remain in first CR 6-49 months after diagnosis. The longest time to relapse without ATRA therapy was 56 months in a patient post-related alloBMT in first CR. The longest time to relapse in a patient who had received ATRA was 46 months. Three patients were treated with arsenic trioxide for relapsed disease but only one achieved a subsequent CR. Stem cell transplantation was performed in 17 patients (11 related allo, 4 auto, 2 VUD), 6 in first CR (prior to the availability of ATRA). Nine patients are still alive (7 related allo, 2 auto), 4 in first CR. The Kaplan-Meier 10 yr event free survival (EFS) and overall survival are 63%. 5 yr EFS for those who received ATRA was 69% compared with 53% for those who did not (p=0.28). Age (gtoreq60 yrs) and WBC count(gtoreq10.0X109/L) had no significant influence on EFS. The presence of additional cytogenetic abnormalities along with t(15;17) had a significant negative influence on EFS of 47% vs. 75% (p=0.04) at 5yrs. Due to small numbers we could not determine the impact of ATRA therapy on APL with additional cytogenetic changes. These results confirm the use of ATRA has a positive influence on outcome, which although currently not statistically significant will likely become so. Furthermore, additional cytogenetic abnormalities may contribute to a poorer outcome; APL as a second malignancy appears highly curable; and time to cytogenetic remission may not have an influence on disease free survival.

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Accession: 035980808

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