CD56 antigen, a 200-220 kDa cell surface glycoprotein, identified as an isoform of the neural adhesion molecules (NCAM), has been found frequently expressed in several lympho-hematopoietic neoplasms including acute myeloid leukemias (AML). In fact, in these latter diseases it has been reported that the presence of CD56 antigen on the blasts of AML patients with t(8;21) (q22;q22), and in those with M3 subtype, identifies a subgroup of patients with a more unfavorable prognosis. On the basis of these findings, we evaluated in 152 newly diagnosed AML patients CD56 surface expression, and results were correlated with morphology, immunophenotype, cytogenetic pattern and clinical outcome. CD56 antigen was recorded in 37 out of 152 cases (24%) and particularly in those with M2 and M5 cytotypes. Moreover, CD56 expression was significantly associated with P-glycoprotein (PGP) hyperexpression (P = 0.007), unfavorable cytogenetic abnormalities (P = 0.008) and with a reduced probability of achieving complete remission (CR) (36% vs 68%) (P = 0.035) as well as with a shorter survival (6 vs 12 months) (P = 0.032). In conclusion, CD56 antigenic expression on AML cells represents an important adverse prognostic factor and therefore its presence should be regularly investigated for a better prognostic assessment of AML patients at diagnosis. Leukemia (2001) 15, 1161-1164.

Summary Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.e. 13q‐single or normal), group 2 (intermediate risk, i.e. +12, 6q‐, 1–2 anomalies), group 3 (unfavourable, i.e. 17p‐, 11q‐, complex karyotype), or group 4 (14q32/IGH translocation). Endpoints were treatment‐free survival (TFS) and overall survival (OS). One hundred and ten patients were included in group 1, 99 in group 2, 25 in group 3 and 18 in group 4. 14q32/IGH translocation partners were identified in eight cases (BCL2 in five cases, BCL11A, CCND3 and CDK6 in one case each). group 4 showed shorter TFS versus groups 2 and 1 (25% patients treated at 2 months vs. 12 (P = 0·02) and 20 months (P = 0·002), respectively) and shorter OS (25% patients dead at 18 months versus 50 (P = 0·0003) and >60 months (P < 0·0001) respectively. The 14q32/IGH translocation maintained prognostic significance at multivariate analysis on TFS (P = 0·025) and OS (P < 0·001), along with advanced stage and CD38+. These findings show that the 14q32/IGH translocation predicts for an unfavourable outcome in CLL and that this cytogenetic subset might be included as a separate entity in a hierarchical cytogenetic classification of CLL.

Thirty untreated patients, median age 69 years (range 60 - 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.

Cytogenetic abnormalities are among the most important factors affecting the outcome of patients with acute myeloid leukaemia (AML), but approximately 40-50% of AML cases display a normal karyotype at diagnosis. Multidrug resistance (MDR) proteins overexpression is associated with worse prognosis in acute leukaemias, but its role in normal karyotype AML is less defined. We analysed the expression of P-glycoprotein (PGP), MDR-related protein (MRP) and lung resistance protein (LRP) in 135 adult patients with normal karyotype AML and its correlation with other biological features of the disease, to evaluate the impact of MDR proteins on response to therapy and on survival. Increased PGP expression was associated with lower rate of complete remission (CR; p = 0.006), similarly to advanced age. Cases overexpressing PGP displayed also a shorter event-free survival (EFS; 4 vs. 10 months, p = 0.035) and the increased expression of at least one MDR protein was associated with a reduced overall survival (OS; p = 0.038). Also age was predictive of worse prognosis. Our data confirm the prognostic role of MDR proteins, in particular of PGP, also in AML patients with normal karyotype at diagnosis. This finding could be used to stratify patients with different prognosis and to design risk-adapted therapeutic strategies.

Fludarabine plus cyclophosphamide (FC) at conventional doses is an effective treatment for chronic lymphocytic leukaemia (CLL). However, FC at standard doses may give hematological and non-hematological toxicity, predominantly in the elderly. Intravenous or oral low-dose FC regimens remain highly effective in elderly patients with Low-Grade Lymphomas other than CLL and are well tolerated. We tested efficacy and toxicity of oral FC at reduced doses in 26 elderly patients (median 71 years) with previously untreated (UT-CLL, n = 14) or relapsed/refractory CLL (R-CLL, n = 12), unfit for conventional treatments. Twentyfour-of-26 (92%) patients (14/14, 100% UT-CLL; 10/12, 83.5% R-CLL) obtained a response, with 12/26 (46%) complete responses (9/14, 64.2% in UT-CLL; 3/12, 25% in R-CLL). Non-hematological toxicity was mild and myelosuppression was documented in 8/26 (31%) patients (4/14, 28% UT-CLL; 4/12, 33% R-CLL). With a median follow-up of 24 months, median event-free survival was 48 months with no differences between UT-CLL and R-CLL and all responders were alive. Low-dose oral FC treatment showed good efficacy in both untreated and refractory/relapsed CLL. The treatment is useful in elderly patients who cannot benefit of more aggressive schedules and is easy to administer on an outpatient basis.