Clinical Features and Prognostic Impact of CD56 Expression in Acute Promyelocytic Leukemia: Long Term Follow up Data From the Japan Adult Leukemia Study Group(JALSG) APL97,
Authors: Ono Takaaki , Takeshita Akihiro , Kishimoto Yuji , Kiyoi Hitoshi , Okada Masaya , Yamauchi Takahiro , Tsuzuki Motohiro , Horikawa Kentaro , Matsuda Mitsuhiro , Shinagawa Katsuji , Monma Fumihiko , Ohtake Shigeki , Nakaseko Chiaki , Takahashi Masatomo , Yagasaki Fumiharu , Kimura Yukihiko , Fujita Hiroyuki , Iwanaga Masako , Asou Norio , Ohnishi Kazunori , Naoe Tomoki 
Published: October 2019

Abstract
Abstract 3608
CD56 expression is reportedly associated with an adverse prognosis in patients with acute promyelocytic leukemia (APL) (Murray et al, 1999, Ferrara et al, 2000), but the prognostic significance of CD56 has not been elucidated in multivariate analysis. Recently, however, Spanish group demonstrated that CD56 expression was a significant adverse prognostic factor for relapse in APL treated with ATRA combined anthracycline-based regimens in multivariate analysis (Montesinos et al, 2011). We tried to evaluate the significance of CD56 in APL on more intensive regimen composed by ATRA, anthracycline and cytosine arabinocide (Ara-C).
Newly diagnosed APL patients were registered to the JALSG APL97 from May 1997 to June 2002. The detail of the treatment protocol was previously reported (Asou et al, 2007). In brief, induction therapy was composed of ATRA and chemotherapy including idarubicin and Ara-C. The dose and duration of induction therapy were based on initial white blood cell (WBC) count. After 3 courses of consolidation therapies, patients were randomly allocated either to receive 6 courses of intensified maintenance chemotherapy or to observation. Leukemia blasts were stained by anti-CD45 monoclonal antibody (mAb), gated by CD45 expression and analyzed by flow cytometer. Cells were additionally stained by fluorescein conjugated mAb against each surface antigen including CD56. Surface markers were defined as positive if more than 20% of APL cells expressed a specific antigen. Clinical characteristics were compared by the chi-square test or the Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous data. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and the log-rank test. Cumulative incidence of relapse (CIR) was compared by the Gray test for comparisons. Multivariate analyses were also performed. Clinical outcomes were renewed on March 2010 and the median follow up period is 7.5 years.
Among 302 patients enrolled, 239 patients were assessable. Twenty three patients (9.6%) were CD56-positive (CD56+) APL. CD56 expression was significantly associated with lower platelet count, serious DIC and expressions of CD2, 7, 34, HLA-DR. (P = 0.04, 0.04, 0.03, 0.04, <0.001 and <0.001, respectively) The CR rate and mortality during induction therapy were not significantly different compared with CD56− APL. CIR and EFS showed inferior trend in CD56+ APL (24.3% vs. 39.1%, P = 0.08 and 64.8% vs. 47.8%, P = 0.08, respectively), whereas cumulative incidence of extramedullary relapse and OS were not different between two groups (P = 0.27 and P = 0.52, respectively). In patients whose initial WBC count was more than 3.0 × 109/L, EFS and CIR for CD56+ group were significantly inferior (28.9% vs. 53.8%, P = 0.03 and 63.6% vs. 30.8%, P = 0.008, respectively), while in patients whose initial WBC count was under 3.0 × 109/L, EFS and CIR were not significantly different (P = 0.99 and P = 0.44, respectively). In multivariate analysis, CD56 expression was an independent prognostic factor for EFS in patients whose initial WBC count was more than 3.0 × 109/L (HR = 3.10; 95% CI, 1.4–7.1, P = 0.007).
CD56+ APL was associated with lower platelet count, serious DIC and expressions of CD2, 7, 34 or HLA-DR. Thus, CD56 expression was an independent adverse prognostic factor for EFS in APL treated by ATRA combined with anthracycline and Ara-C regimen, especially in APL whose initial WBC count is more than 3.0 × 109/L. The prognostic significance of CD56 expression should be continuously monitored in future.

Disclosures:
Takeshita: Takeda: Research Funding; Novaltis: Research Funding. Naoe:Kyowa-Hakko Kirin.: Research Funding; Dainipponn-Sumitomo Pharma.: Research Funding; Chugai Pharma.: Research Funding; Novartis Pharma.: Honoraria, Speakers Bureau; Zenyaku-Kogyo: Research Funding; Otsuka Pharma.: Research Funding.