No abstract

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)

BackgroundFms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and MethodsWe evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis. ConclusionsFLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens. monochemotherapy. Haematologica 2011;96(10):1470-1477. doi:10.3324/haematol.2011 This is an open-access paper.

Fludarabine produces high response rates in patients with B-cell chronic lymphocytic leukemia (CLL). Nevertheless, response to fludarabine of patients with previously treated CLL varies from 17% to 74% (0% to 38% CR). In 68 patients with heavily pretreated and advanced CLL, an overall response rate to fludarabine of 28% (4% CR) was observed. Response correlated with sensitivity of the disease to previous treatments (relapsing vs. refractory disease) (62% vs. 20%; p = 0.005) and, albeit not significantly, with the number of cycles of fludarabine (>3 vs. < or = 3) that patients could receive (36% vs. 15%; p = NS). Responding patients had a longer survival (median, not reached) than those not responding (median, 11 months) (p = 0.03). Severe toxicity was observed in some cases. It is concluded that fludarabine is a highly useful agent in CLL. However, in order to improve its effectiveness and decrease its toxicity, fludarabine should be given as soon as a lack of response to front-line therapy is observed and before the disease becomes completely resistant to therapy.

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of !2 ACA, and a very CK (CKþ) as !3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CKþ. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with <2 ACA (p¼.09). Among patients with CKþ, the 5-year CIR was 27% vs 12% (p¼.003), retaining the statistical significance in multivariate analysis. This study shows an increased risk of relapse among APL patients with CK þ treated with ATRA plus chemotherapy front-line regimens.