The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthracycline-based regimens. Between 1996 and 2009, 651 APL patients with available data on CD56 expression were included in 3 subsequent trials (PETHEMA LPA96 and LPA99 and PETHEMA/HOVON LPA2005). Seventytwo patients (11%) were CD56 ؉ (expression of CD56 in > 20% leukemic promyelocytes). CD56 ؉ APL was significantly associated with high white blood cell counts; low albumin levels; BCR3 isoform; and the coexpression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. For CD56 ؉ APL, the 5-year relapse rate was 22%, compared with a 10% relapse rate for CD56 ؊ APL (P ‫؍‬ .006). In the multivariate analysis, CD56 expression retained the statistical significance together with the relapse-risk score. CD56 ؉ APL also showed a greater risk of extramedullary relapse (P < .001). In summary, CD56 expression is associated with the coexpression of immaturity-associated and T-cell antigens and is an independent adverse prognostic factor for relapse in patients with APL treated with all-trans-retinoic acid plus idarubicin-derived regimens. This marker may be considered for implementing riskadapted therapeutic strategies in APL. The LPA2005 trial is registered at http:// www.clinicaltrials.gov as NCT00408278. (Blood. 2011;117(6):1799-1805)

We conducted a large international nested case-control study including 1,881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n=647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer and melanoma) and controls (n=1,234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR=1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had twofold higher risk of non-melanoma (NM) skin cancer (OR=2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR=3.74, 95% CI 1.00-14.01), ruxolitinib (OR=3.87, 95% CI 1.18-12.75) and for drug combination (OR=3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.