APL, Information and SupportInspired by Anita’s Journey through Acute Promyelocytic Leukemia

I spotted this article a few days ago on the ASH website. The article discusses a group of investigators in China that treated 60 APL patients, mainly with ATRA and Arsenic – with no use of traditional chemotherapy such as Ara-C and Idarubicin. Leave it to the Chinese to try something radical like this – they often seem to march to their own drum.

Of course they were likely treating APL with Arsenic close to 2,000 years ago but didn’t know it was called “APL” back then!

The 60 patients will have to be followed over a longer term but it is interesting to see the success the article reports.

Seeing this article makes me wonder if the continued use of traditional chemo for APL might be at least somewhat rooted in practices that existed before the advent of ATRA and arsenic.

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From the American Society of Hematology 2006 conference

Investigators at the MD Anderson Cancer Center showed that patients with acute promyelocytic leukemia (APL), not ideally suited for chemotherapy, can experience a high rate of complete remission and high likelihood of disease-free survival, albeit with short follow-up, if treated only with all trans-retinoic acid (ATRA) and arsenic trioxide as front-line therapy.[18]

Liu and colleagues[19] from Shanghai, China, presented a cohort of 60 patients treated with 25 mg/m2 oral ATRA plus 0.16 mg/kg intravenous arsenic trioxide daily until complete remission was achieved. Then, 3 courses of consolidation chemotherapy were given, followed by 5 cycles of sequential treatment with ATRA, arsenic trioxide, and 6MP/methotrexate.

In all, 93% of patients achieved remission within a median time to complete remission of 27 days. Two of these patients experienced extramedullary relapse, but all the remaining patients were alive and in a hematologic remission, yielding a 4-year overall and event-free survival of 98% and 94%, respectively.

The most comprehensive randomized study comparing standard ATRA/chemotherapy with ATRA/chemotherapy/arsenic is CALGB 9710, an intergroup study in which patients received 3+7 chemotherapy plus ATRA during induction and then were randomized to receive standard consolidation therapy with ATRA/anthracycline preceded (or not) by arsenic trioxide.

Although the final results of this study were not presented at ASH, Dr. Powell did report aggregate toxicities from this study[20] that indicated that only 10 of the 518 adults and none of the 64 children enrolled experienced a lethal event during induction. The overall results also confirmed the validity of the European risk stratification scheme that defined 3 risk groups: low-risk patients, white count < 10,000 and a platelet count > 40,000; intermediate-risk patients, white count < 10,000 and a platelet count < 40,000; and high-risk patients, white count > 10,000. There was a high rate of induction death and relapse in the high-risk group. This study suggested that if arsenic trioxide is confirmed as therapeutically beneficial in terms of disease-free survival, then the toxicity will be acceptable.

Some interesting molecular correlates of treating patients with APL were presented.[21,22] Prior results indicating that the presence of detectable disease via PCR analysis for the PML-RAR alpha transcript would predict for relapse were not confirmed when a quantitative PCR analysis was employed. A single post-consolidation time point did not predict relapse of APL in patients. A more sensitive assay might improve relapse prediction rate, but this would need to be confirmed with further testing.

The Spanish PETHEMA group[23] demonstrated a very high rate of long-term disease-free survival in APL using retinoic acid plus chemother